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.

[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 suggests that the binary is part of the young disk population which agrees with the high Li I lambda 6708 abundance. With the M star companion showing very high levels of activity it seems likely that the V824 Ara +LDS587B system is pre-main sequence. With rotational velocities of 37 km/s and 29 km/s for the G and K star components respectively, the system is very similar to V711 Tau. Photometric observations by Cutispoto (1993) show an amplitude, delta V approx. = 0.12 with a period equal to the orbital value derived by Pasquini et at. (1991). Dempsey et al. (1993a) found a PSPC X-ray luminosity of 2.74 x 10(exp 30)erg/s. Two-temperature coronal models were applied to the PSPC X-ray pulse-height spectra by Dempsey et al. (1993b). They found that the lower temperature component was consistent with the full sample of RS CVn binaries studied but that the hot component was slightly lower than the sample as a whole. Moderate Ca II H and K emission, filled in H alpha and radio emission are also consistent with this being a fairly active, short period binary system.

Time-series photometric spot modeling. 2: Fifteen years of photometry of the bright RS CVn binary HR 7275

NASA Technical Reports Server (NTRS)

Strassmeier, K. G.; Hall, D. S.; Henry, G. W.

1994-01-01

We present a time-dependent spot modeling analysis of 15 consecutive years of V-band photometry of the long-period (P(sub orb) = 28.6 days) RS CVn binary HR 7275. This baseline in time is one of the longest, uninterrupted intervals a spotted star has been observed. The spot modeling analysis yields a total of 20 different spots throughout the time span of our observations. The distribution of the observed spot migration rates is consistent with solar-type differential rotation and suggests a lower limit of the differential-rotation coefficient of 0.022 +/-0.004. The observed, maximum lifetime of a single spot (or spot group) is 4.5 years, the minimum lifetime is approximately one year, but an average spot lives for 2.2 years. If we assume that the mechanical shear by differential rotation sets the upper limit to the spot lifetime, the observed maximum lifetime in turn sets an upper limit to the differential-rotation coefficient, namely 0.04 +/- 0.01. This would be differential rotation just 5 to 8 times less than the solar value and one of the strongest among active binaries. We found no conclusive evidence for the existence of a periodic phenomenon that could be attributed to a stellar magnetic cycle.

Investigating ChaMPlane X-Ray Sources in the Galactic Bulge with Magellan LDSS2 Spectra

NASA Astrophysics Data System (ADS)

Koenig, Xavier; Grindlay, Jonathan E.; van den Berg, Maureen; Laycock, Silas; Zhao, Ping; Hong, JaeSub; Schlegel, Eric M.

2008-09-01

We have carried out optical and X-ray spectral analyses on a sample of 136 candidate optical counterparts of X-ray sources found in five Galactic bulge fields included in our Chandra Multiwavelength Plane Survey. We use a combination of optical spectral fitting and quantile X-ray analysis to obtain the hydrogen column density toward each object, and a three-dimensional dust model of the Galaxy to estimate the most probable distance in each case. We present the discovery of a population of stellar coronal emission sources, likely consisting of pre-main-sequence, young main-sequence, and main-sequence stars, as well as a component of active binaries of RS CVn or BY Dra type. We identify one candidate quiescent low-mass X-ray binary with a subgiant companion; we note that this object may also be an RS CVn system. We report the discovery of three new X-ray-detected cataclysmic variables (CVs) in the direction of the Galactic center (at distances lesssim2 kpc). This number is in excess of predictions made with a simple CV model based on a local CV space density of lesssim10-5 pc-3, and a scale height ~200 pc. We discuss several possible reasons for this observed excess.

Radio wavelength observations of magnetic fields on active dwarf M, RS CVn and magnetic stars

NASA Technical Reports Server (NTRS)

Lang, Kenneth R.

1986-01-01

The dwarf M stars, YZ Canis Minoris and AD Leonis, exhibit narrow-band, slowly varying (hours) microwave emission that cannot be explained by conventional thermal radiation mechanisms. The dwarf M stars, AD Leonis and Wolf 424, emit rapid spikes whose high brightness temperatures similarly require a nonthermal radiation process. They are attributed to coherent mechanisms such as an electron-cyclotron maser or coherent plasma radiation. If the electron-cyclotron maser emits at the second or third harmonic gyrofrequency, the coronal magnetic field strength equals 250 G or 167 G, and constraints on the plasma frequency imply an electron density of 6 x 10 to the 9th/cu cm. Radio spikes from AD Leonis and Wolf 424 have rise times less than or equal to 5 ms, indicating a linear size of less than or equal to 1.5 x 10 to the 8th cm, or less than 0.005 of the stellar radius. Although Ap magnetic stars have strong dipole magnetic fields, they exhibit no detectable gyroresonant radiation, suggesting that these stars do not have hot, dense coronae. The binary RS CVn star UX Arietis exhibits variable emission at 6 cm wavelength on time scales ranging from 30 s to more than one hour.

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.

The enigmatic star EZ Pegasi - A mystery solved?

NASA Technical Reports Server (NTRS)

Howell, S. B.; Bopp, B. W.

1985-01-01

EZ Peg, a ninth-magnitude G star that has been classified by various authors as an irregular variable, a U Gem system, and a contact binary, is shown to have all the spectroscopic and photometric characteristics of an active-chromosphere RS CVn binary. It is suggested that the reported outburst of 1943, when the spectrum appeared to be that of a B star, never occurred. The strong Ca II H and K reversals, viewed with low spectral resolution, caused the photospheric Ca II absorption to appear abnormally weak, mimicking a much earlier spectral type.

Definition and empirical structure of the range of stellar chromospheres-coronae across the H-R diagram: Cool stars

NASA Technical Reports Server (NTRS)

Linsky, J. L.

1986-01-01

Major advances in our understanding of non-radiative heating and other activity in stars cooler than T sub eff = 10,000K has occured in the last few years. This observational evidence is reviewed and the trends that are now becoming apparent are discussed. The evidence for non-radiatively heated outer atmospheric layers (chromospheres, transition regions, and coronae) in dwarf stars cooler than spectral type A7, in F and G giants, pre-main sequence stars, and close bindary systems is unambiguous, as is the evidence for chromospheres in the K and M giants and supergiants. The existence of non-radiative heating in the outer layers of the A stars remains undetermined despite repeated searches at all wavelengths. Two important trends in the data are the decrease in plasma emission measure with age on the main sequence and decreasing rotational velocity. Variability and atmospheric inhomogeneity are commonly seen, and there is considerable evidence that magnetic fields define the geometry and control the energy balance in the outer atmospheric layers. In addition, the microwave observations imply that non-thermal electrons are confined in coronal magnetic flux tubes in at least the cool dwarfs and RS CVn systems. The chromospheres in the K and M giants and supergiants are geometrically extended, as are the coronae in the RS CVn systems and probably also in other stars.

Coordinated XTE Observations of Coronal Structure and Flares on the Rs CVn Binary Sigma(sup 2) CrB

NASA Technical Reports Server (NTRS)

Brown, Alexander

1999-01-01

This NASA grant supported my RXTE observing and data analysis during AO2. The research involved a 100 kilosecond observation of the active RS CVn binary sigma(sup 2) CrB obtained on 1997 March 11-13. This observation covered two orbits of the binary (2.5 days elapsed time) as part of a coordinated satellite and ground-based study of coronal structure and flaring within this system. Simultaneous data was obtained from the ASCA X-ray satellite and the Very Large Array radio telescope. The one month of effort funded for the PI was used to calibrate and analyze the RXTE data. Additional research effort on this project to lead to a final publication has been provided from LTSA and GSRP grants. An initial attempt was made to calibrate the RXTE data in May 1997 but the results were disappointing with poor background subtraction leading to a relatively noisy PCA light curve. Subsequently major improvements have been made in the calibration techniques for low count rate PCA data and we returned to Goddard Space Flight Center in February 1999 when we were able to produce vastly better calibrated data. The RXTE results are currently being integrated with the ASCA and VLA data and a paper should be submitted by the end of summer 1999.

NICER and MAXI Observations of Two Large X-ray Flares from RS CVn Binaries

NASA Astrophysics Data System (ADS)

Drake, Stephen A.; Hamaguchi, Kenji; Corcoran, Michael Francis; Iwakiri, Wataru; Sasaki, Ryo; Kawai, Hiroki; Tsuboi, Yohko; Enoto, Teruaki; NICER Science Team

2018-01-01

NICER has observed two giant X-ray flares on the active binary systems, GT Mus and UX Ari, in response to their detections by the MAXI all-sky X-ray monitor onboard the ISS, with a delay of about a day in each case. The large effective area of the NICER X-ray optics means that high signal-to-noise spectra with more than 200,000 counts were obtained in relatively short exposures totaling less than an hour in each set of observations.MAXI detected a transient of 5.5 x 10^-10 erg/s/cm2 at the position of the active RS CVn binary GT Mus (G5/8 III + ?) early on 2017 July 19. NICER started its observations about 1 day later, and intermittently monitored the decay for the next 2.5 days, accumulating about 1,600 seconds exposure. The NICER light curve shows a smooth, gradual flux decline by a factor of two for the first 2 days, followed by an apparent flattening in the last half day. The dominant plasma temperature remained at ~40 million K during this period, suggesting an ongoing continuous heating during the decay phase.NICER also followed up another MAXI-detected flare in October 2017, this one from the nearby active system, UX Ari. NICER's X-ray spectrum shows clear neon and oxygen lines, while the emissionfrom iron ions is not as prominent as it is in most flares, implying an abundance of only ~10% solar which is significantly lower than previous inferred coronal Fe abundances for this star, although this result is dependent on the NICER gain correction.

Cool Spot and Flare Activities of a RS CVn Binary KIC 7885570

NASA Astrophysics Data System (ADS)

Kunt, M.; Dal, H. A.

2017-12-01

We present here the results of our studies on the physical nature and chromospheric activity of a RS CVn binary KIC 7885570 based on the Kepler Mission data. Assuming the primary component temperature, 6530 K, the temperature of the secondary component was found to be 5732±4 K. The mass ratio of the components (q) was found to be 0.43±0.01, while the inclination (i) of the system - 80.6°±0.1°. Additionally, the data were separated into 35 subsets to model the sinusoidal variation due to the rotational modulation, using the SpotModel program, as the light curve analysis indicated the chromospherically active secondary component. It was found that there are generally two spotted areas, whose radii, longitudes and latitudes are rapidly changing, located around the latitudes of +50° and +90° on the active component. Moreover, 113 flares were detected and their parameters were computed from the available data. The One Phase Exponential Association function model was derived from the parameters of these flares. Using the regression calculations, the Plateau value was found to be 1.9815±0.1177, while the half-life value was computed as 3977.2 s. In addition, the flare frequency (N1) - the flare number per hour, was estimated to be 0.00362 h-1, while flare frequency (N2) - the flare-equivalent duration emitted per hour, was computed as 0.00001. Finally, the times of eclipses were computed for 278 minima of the light curves, whose analysis indicated that the chromosphere activity nature of the system causes some effects on these minima times. Comparing the chromospheric activity patterns with the analogues of the secondary component, it is seen that the magnetic activity level is remarkably low. However, it is still at the expected level according to the B-V color index of 0.643 mag for the secondary component.

The scientific results of the low energy portion of A-2

NASA Technical Reports Server (NTRS)

Garmire, G.

1979-01-01

Galactic phenomena observed using the HEAO 1 detectors are discussed. A source map of the soft X-ray sky is presented. Specific topics covered include the optical outburst of U Geminorum, low energy RS CVn stars, and the dwarf nova SS Cygni. Aspects of the SS Cygni pulsations are analyzed.

Two component X-ray emission from RS CVn binaries

NASA Technical Reports Server (NTRS)

Swank, J. H.; White, N. E.; Holt, S. S.; Becker, R. H.

1980-01-01

A summary of results from the solid state spectrometer on the Einstein Observatory for 7 RS CVn binaries is presented. The spectra of all require two emission components, evidenced by line emission characteristic of plasma at 4 to 8 x 10 to the 6th power and bremsstrahlung characteristic of 20 to 100 x 10 to the 6th power K. The data are interpreted in terms of magnetic coronal loops similar to those seen on the Sun, although with different characteristic parameters. The emission regions could be defined by separate magnetic structures. For pressure less than approximately 10 dynes/sq cm the low temperature plasma would be confined within the stellar radii, while the high temperature plasma would, for the synchronous close binaries, fill the binary orbits. However, for loop pressures exceeding 100 dynes/sq cm, the high temperature components would also be confined to within the stellar radii, in loops covering only small fractions of the stellar surfaces. While the radio properties and the occurrence of X-ray flares suggest the larger emission regions, the observations of time variations leave the ambiguity unresolved.

25 new chromospherically active stars in the ROTSE-1 data base

NASA Astrophysics Data System (ADS)

Bernhard, Klaus; Lloyd, Christopher

2008-03-01

25 new chromospherically active stars are presented, which were found in the ROTSE-1 data base: GSC 4721-00552, GSC 2518-00781, GSC 2628-01345, GSC 164-01162, GSC 3345-01977, GSC 3525-01869, GSC 2912-01219, GSC 115-00801, GSC 3333-00117, GSC 1979-00569, GSC 1291-00887, GSC 2229-00611, GSC 105-00869, GSC 63-00006, GSC 5253-00472, GSC 2339-01230, GSC 4920-01189, GSC 1164-00392, GSC 1756-00430, GSC 2276-00205, GSC 2280-00897, GSC 234-00306, GSC 4912-01357, GSC 612-00169, GSC 1935-01066 One of these variables (No.4: GSC 164-01162) is a new long-period eclipsing RS CVn variable.

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

X-ray and radio observations of flares from the RS Canum Venaticorum system UX ARIETIS

NASA Astrophysics Data System (ADS)

Tsuru, T.; Makishima, K.; Ohashi, T.; Inoue, H.; Koyama, K.; Turner, M. J. L.; Barstow, M. A.; McHardy, I. M.; Pye, J. P.; Tsunemi, H.; Kitamoto, S.; Taylor, A. R.; Nelson, R. F.

In July 1987 the RS CVn system UX Ari was observed in the 2-20-keV X-ray band by Ginga, immediately followed by 5-GHz radio observations. UX Ari was found to be very active at both radio and X-ray frequencies. Quiescent X-ray emission with a luminosity of 3 x 10 to the 31st erg/s (in the 2-20-keV band) was detected, together with two intense X-ray flares up to 2 x 10 to the 32nd and 6 x 10 to the 31st erg/s, respectively. Both flare and quiescent X-ray spectra are well fitted by single-temperature thermal bremsstrahlung models, with the continuum temperature and emission measure in the range 4-7 kev (in kT) and (2-10) x 10 to the 54th/cu cm, respectively.

Responses of Caudal Vestibular Nucleus Neurons of Conscious Cats to Rotations in Vertical Planes, Before and After a Bilateral Vestibular Neurectomy

PubMed Central

Miller, D. M.; Cotter, L. A.; Gandhi, N. J.; Schor, R. H.; Cass, S. P.; Huff, N. O.; Raj, S. G.; Shulman, J. A; Yates, B. J.

2008-01-01

Although many previous experiments have considered the responses of vestibular nucleus neurons to rotations and translations of the head, little data are available regarding cells in the caudalmost portions of the vestibular nuclei (CVN), which mediate vestibulo-autonomic responses among other functions. This study examined the responses of CVN neurons of conscious cats to rotations in vertical planes, both before and after a bilateral vestibular neurectomy. None of the units included in the data sample had eye movement-related activity. In labyrinth-intact animals, some CVN neurons (22%) exhibited graviceptive responses consistent with inputs from otolith organs, but most (55%) had dynamic responses with phases synchronized with stimulus velocity. Furthermore, the large majority of CVN neurons had response vector orientations that were aligned either near the roll or vertical canal planes, and only 18% of cells were preferentially activated by pitch rotations. Sustained head-up rotations of the body provide challenges to the cardiovascular system and breathing, and thus the response dynamics of the large majority of CVN neurons were dissimilar to those of posturally-related autonomic reflexes. These data suggest that vestibular influences on autonomic control mediated by the CVN are more complex than previously envisioned, and likely involve considerable processing and integration of signals by brainstem regions involved in cardiovascular and respiratory regulation. Following a bilateral vestibular neurectomy, CVN neurons regained spontaneous activity within 24 h, and a very few neurons (<10%) responded to vertical tilts <15° in amplitude. These findings indicate that nonlabyrinthine inputs are likely important in sustaining the activity of CVN neurons; thus, these inputs may play a role in functional recovery following peripheral vestibular lesions. PMID:18368395

The Soft X-Ray/Microwave Ratio of Solar and Stellar Flares and Coronae

NASA Technical Reports Server (NTRS)

Benz, A. O.; Guedel, M.

1994-01-01

We have carried out plasma diagnostics of solar flares using soft X-ray (SXR) and simultaneous microwave observations and have compared the ratio of X-ray to microwave luminosities of solar flares with various active late-type stars available in the published literature. Both the SXR low-level ('quiescent') emission from stellar coronae and the flaring emission from the Sun and stars are generally interpreted as thermal radiations of coronal plasmas. On the other hand, the microwave emission of stars and solar flares is generally attributed to an extremely hot or nonthermal population of electrons. Solar flare SXR are conventionally measured in a narrower and harder passband than the stellar sources. Observations of the GOES-2 satellite in two energy channels have been used to estimate the luminosity of solar flares as it would appear in the ROSAT satellite passband. The solar and stellar flare luminosities fit well at the lower end of the active stellar coronae. The flare SXR/microwave ratio is similar to the ratio for stellar coronae. The average ratio follows a power-law relation L(sub X) varies as L(sub R)(sup 0.73 +/- 0.03) over 10 orders of magnitude from solar microflares to RS CVn and FK Com-type coronae. Dwarf Me and Ke stars, and RS CVn stars are also compatible with a linear SXR/microwave relation, but the ratio is slightly different for each type of star. Considering the differences between solar flares, stellar flares and the various active stellar coronae, the similarity of the SXR/microwave ratios is surprising. It suggests that the energetic electrons in low-level stellar coronae observed in microwaves are related in a similar way to the coronal thermal plasma as flare electrons to the flare thermal plasma, and, consequently, that the heating mechanism of active stellar coronae is a flare-like process.

Fast transient X-rays and gamma ray bursts - Are they stellar flares?

NASA Astrophysics Data System (ADS)

Rao, A. R.; Vahia, M. N.

Short period transient X-ray emissions (FTX) have been observed from several sources in the sky and the largest single group of objects identified with such sources are active stars: flare stars, and RS CVn binaries. The study of the number, source and flux distribution of the fast transient X-ray sources shows that all the FTX emission can be treated as flares in the interbinary regions of active stars. It is suggested that the FTX emission is a common feature of the gamma ray bursts (GRBs). The evidence for the similarity between the hard X-ray flares and GRBs is discussed, and the possibility that the gamma ray bursts are the impulsive precursors of FTX originating from active stars with large scale magnetic activity is examined.

VizieR Online Data Catalog: Chromospherically Active Binaries. Third version (Eker+, 2008)

NASA Astrophysics Data System (ADS)

Eker, Z.; Filiz-Ak, N.; Bilir, S.; Dogru, D.; Tuysuz, M.; Soydugan, E.; Bakis, H.; Ugras, B.; Soydugan, F.; Erdem, A.; Demircan, O.

2008-06-01

Chromospherically Active Binaries (CAB) catalogue have been revised and updated. With 203 new identifications, the number of CAB stars is increased to 409. Catalogue is available in electronic format where each system has various number of lines (sub-orders) with a unique order number. Columns contain data of limited number of selected cross references, comments to explain peculiarities and position of the binarity in case it belongs to a multiple system, classical identifications (RS CVn, BY Dra), brightness and colours, photometric and spectroscopic data, description of emission features (Ca II H&K, Hα, UV, IR), X-Ray luminosity, radio flux, physical quantities and orbital information, where each basic entry are referenced so users can go original sources. (10 data files).

SS Bootis - A totally eclipsing binary of the RS CVn type

NASA Technical Reports Server (NTRS)

Vaucher, C. A.; Africano, J. L.; Henry, G. W.; Hall, D. S.; Wilson, J. W.

1983-01-01

Photoelectric photometry gathered for SS Bootis over the 1976-1981 period shows a distortion wave amplitude variation from 0.05 to 0.20 mag, with no apparent pattern. From the rectified light curve, a new time of midprimary eclipse was found to be 2444332.0335 + or - 0.0005 days. Solutions of the primary eclipse data, rectified for star spots as well as for ellipticity and reflection, are presented.

VizieR Online Data Catalog: Excess CaII H&K emission in active binaries (Montes+, 1996)

NASA Astrophysics Data System (ADS)

Montes, D.; Fernandez-Figueroa, M. J.; Cornide, M.; de Castro, E.

1996-05-01

In this work we analyze the behaviour of the excess CaII H & K and H_epsilon emissions in a sample of 73 chromospherically active binary systems (RS CVn and BY Dra classes), of different activity levels and luminosity classes. This sample includes the 53 stars analyzed by Fernandez-Figueroa et al. (1994) and the observations of 28 systems described by Montes et al. (1995). By using the spectral subtraction technique (subtraction of a synthesized stellar spectrum constructed from reference stars of spectral type and luminosity class similar to those of the binary star components) we obtain the active-chromosphere contribution to the CaII H & K lines in these 73 systems. We have determined the excess CaII H & K emission equivalent widths and converted them into surface fluxes. The emissions arising from each component were obtained when it was possible to deblend both contributions. (4 data files).

Artificial neural networks using complex numbers and phase encoded weights.

PubMed

Michel, Howard E; Awwal, Abdul Ahad S

2010-04-01

The model of a simple perceptron using phase-encoded inputs and complex-valued weights is proposed. The aggregation function, activation function, and learning rule for the proposed neuron are derived and applied to Boolean logic functions and simple computer vision tasks. The complex-valued neuron (CVN) is shown to be superior to traditional perceptrons. An improvement of 135% over the theoretical maximum of 104 linearly separable problems (of three variables) solvable by conventional perceptrons is achieved without additional logic, neuron stages, or higher order terms such as those required in polynomial logic gates. The application of CVN in distortion invariant character recognition and image segmentation is demonstrated. Implementation details are discussed, and the CVN is shown to be very attractive for optical implementation since optical computations are naturally complex. The cost of the CVN is less in all cases than the traditional neuron when implemented optically. Therefore, all the benefits of the CVN can be obtained without additional cost. However, on those implementations dependent on standard serial computers, CVN will be more cost effective only in those applications where its increased power can offset the requirement for additional neurons.

Copernicus observations of Ly-alpha and Mg II emission from HR 1099 /V711 Tauri/ and UX Ari

NASA Technical Reports Server (NTRS)

Weiler, E. J.

1978-01-01

Ultraviolet observations of two RS CVn binaries obtained with Copernicus are described. High-resolution (0.05 A) U1 observations indicate that both HR 1099 and UX Ari display broad Ly-alpha emission. The Ly-alpha emission strength from HR 1099 is variable and seems to be correlated with orbital phase, while the UX Ari results indicate no significant variation. Moderate resolution (0.51 A) V2 scans of both systems show variable Mg II h and k emission-line profiles which usually matched the velocity of the more active star in each binary. Additionally, displaced emission components were seen at velocities of up to + or - 250 km/s, indicative of high-velocity gas motions. The radial velocities of these emission features from HR 1099 are marginally correlated with orbital phase. Highly active and variable chromospheric phenomena are found to be the most consistent explanation of these results.

Activity in X-ray-selected late-type stars

NASA Technical Reports Server (NTRS)

Takalo, Leo O.; Nousek, J. A.

1988-01-01

A spectroscopic study has been conducted of nine X-ray bright late-type stars selected from two Einstein X-ray surveys: the Columbia Astrophysical Laboratory Survey (five stars) and the CFA Medium Sensitivity Survey (MSS; four stars). Spectral classes were determined and radial and V sin(i) velocities were measured for the stars. Four of the Columbia Survey stars were found to be new RS CVn-type binaries. The fifth Columbia survey star was found to be an active G dwarf star without evidence for binarity. None of the four MSS stars were found to be either binaries or optically active stars. Activity in these stars was assessed by measuring the excess emission in H-alpha and the Ca II IRT (8498, 8542) lines in comparison with inactive stars of similar spectral types. A correlation was found between X-ray luminosity and V sin(i) and H-alpha line excess. The measured excess line emission in H-alpha was also correlated with V sin(i) but not with the IRT line excess.

Detecting the Companions and Ellipsoidal Variations of RS CVn Primaries. II. o Draconis, a Candidate for Recent Low-mass Companion Ingestion

NASA Astrophysics Data System (ADS)

Roettenbacher, Rachael M.; Monnier, John D.; Fekel, Francis C.; Henry, Gregory W.; Korhonen, Heidi; Latham, David W.; Muterspaugh, Matthew W.; Williamson, Michael H.; Baron, Fabien; ten Brummelaar, Theo A.; Che, Xiao; Harmon, Robert O.; Schaefer, Gail H.; Scott, Nicholas J.; Sturmann, Judit; Sturmann, Laszlo; Turner, Nils H.

2015-08-01

To measure the stellar and orbital properties of the metal-poor RS CVn binary o Draconis (o Dra), we directly detect the companion using interferometric observations obtained with the Michigan InfraRed Combiner at Georgia State University's Center for High Angular Resolution Astronomy (CHARA) Array. The H-band flux ratio between the primary and secondary stars is the highest confirmed flux ratio (370 ± 40) observed with long-baseline optical interferometry. These detections are combined with radial velocity data of both the primary and secondary stars, including new data obtained with the Tillinghast Reflector Echelle Spectrograph on the Tillinghast Reflector at the Fred Lawrence Whipple Observatory and the 2 m Tennessee State University Automated Spectroscopic Telescope at Fairborn Observatory. We determine an orbit from which we find model-independent masses and ages of the components ({M}A=1.35+/- 0.05 {M}⊙ , {M}B=0.99+/- 0.02 {M}⊙ , system age = 3.0\\mp 0.5 Gyr). An average of a 23-year light curve of o Dra from the Tennessee State University Automated Photometric Telescope folded over the orbital period newly reveals eclipses and the quasi-sinusoidal signature of ellipsoidal variations. The modeled light curve for our system's stellar and orbital parameters confirm these ellipsoidal variations due to the primary star partially filling its Roche lobe potential, suggesting most of the photometric variations are not due to stellar activity (starspots). Measuring gravity darkening from the average light curve gives a best-fit of β =0.07+/- 0.03, a value consistent with conventional theory for convective envelope stars. The primary star also exhibits an anomalously short rotation period, which, when taken with other system parameters, suggests the star likely engulfed a low-mass companion that had recently spun-up the star.

Optical flare events on the RS Canum Venaticorum star UX Arietis

NASA Astrophysics Data System (ADS)

Cao, Dong-Tao; Gu, Sheng-Hong

2017-05-01

Based on long-term high-resolution spectroscopic observations obtained during five observing runs from 2001 to 2004, we study optical flare events and chromospheric activity variability of the very active RS CVn star UX Ari. By means of the spectral subtraction technique, several optical chromospheric activity indicators (including the He i D3, Na i D1, D2 doublet, Hα and Ca ii IRT lines) covered in our echelle spectra were analyzed. Four large optical flare events were detected on UX Ari during our observations, which show prominent He i D3 line emission together with great enhancement in emission of the Hα and Ca ii IRT lines and strong filled-in or emission reversal features in the Na i D1, D2 doublet lines. The newly detected flares are much more energetic than previous discoveries, especially for the flare identified during the 2002 December observing run. Optical flare events on UX Ari are more likely to be observed around two quadratures of the system, except for our optical flares detected during the 2004 November observing run. Moreover, we have found rotational modulation of chromospheric activity in the Hα and Ca ii IRT lines, which suggests the presence of chromospherically active longitudes over the surface of UX Ari. The change in chromospherically active longitudes among our observing runs, as well as the variation in chromospheric activity level from 2001 to 2004, indicates a long-term evolution of active regions.

A flare event of the long-period RS Canum Venaticorum system IM Pegasi

NASA Technical Reports Server (NTRS)

Buzasi, Derek L.; Ramsey, Lawrence W.; Huenemoerder, David P.

1987-01-01

The characteristics of a flare event detected on the long-period RS CVn system IM Pegasi are reported. The low-resolution spectrum show enhancements of up to a factor of five in some emission lines. All of the ultraviolet emission lines normally visible are enhanced significantly more than the normal 30 rotational modulation. Emission fluxes of both the quiescent and flare event are used to construct models of the density and temperature variation with height. These models reveal a downward shift of the transition region during the flare. Scaled models of the quiet and flaring solar outer atmosphere are used to estimate the filling factor of the flare event at about 30 percent of the stellar surface. The pattern of line enhancements in the flare is the same as a previous event in Lambda Andromeda observed previously.

Cool stars, stellar systems, and the sun; Proceedings of the 7th Cambridge Workshop, Tucson, AZ, Oct. 9-12, 1991

NASA Technical Reports Server (NTRS)

Giampapa, Mark S. (Editor); Bookbinder, Jay A. (Editor)

1992-01-01

Consideration is given to HST observations of late-type stars, molecular absorption in the UV spectrum of Alpha Ori, EUV emission from late-type stars, Rosat observations of the Pleiades cluster, a deep ROSAT observation of the Hyades cluster, optical spectroscopy detected by EXOSAT, stellar photospheric convection, a structure of the solar X-ray corona, magnetic surface images of the BY Dra Star HD 82558, a Zebra interpretatin of BY Dra stars, optical flares on II Peg, a low-resolution spectroscopic survey of post-T tauri candidates, millimeter and sub-millimeter emission from flare stars, and activity in tidally interacting binaries. Attention is also given to modeling stellar angular momentum evolution, extended 60-micron emission from nearby Mira variables, the PANDORA atmosphere program, the global properties of active regions, oscillations in a stratified atmosphere, lithium abundances in northern RS CVn binaries, a new catalog of cool dwarf stars, the Far UV Spectrograph Explorer, and development of reflecting coronagraphs.

Period changes of the sample of eclipsing binaries with active chromospheres

NASA Astrophysics Data System (ADS)

Jableka, D.; Zola, S.; Zakrzewski, B.; Szymanski, T.; Kuzmicz, A.; de Villiers, S. N.; Zejda, M.; Koziel-Wierzbowska, D.

2012-11-01

In this work we present results derived from analysis of the O-C behaviour of ten eclipsing binary systems: AR Lac, CG Cyg, HP Aur, MM Her, RS CVn, RT And, SV Cam, V471 Tau, WW Dra and CF Tuc. It was proved on the basis of moments of minima compiled from the literature and new ones determined from recent observations, that these binaries show long term (19-91 years) modulations of their orbital periods, clearly visible in their O-C diagrams. Two possible explanations for this effect are considered: (1) the light-travel time effect due to the presence of a third body orbiting the eclipsing systems; (2) the Applegate mechanism predicting period modulation by changes in the distribution of angular momentum as a star goes through its activity cycles. It was found that in the case of four systems the existence of a third star, orbiting the binary, is a more plausible explanation of observations.

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.

The Software Correlator of the Chinese VLBI Network

NASA Technical Reports Server (NTRS)

Zheng, Weimin; Quan, Ying; Shu, Fengchun; Chen, Zhong; Chen, Shanshan; Wang, Weihua; Wang, Guangli

2010-01-01

The software correlator of the Chinese VLBI Network (CVN) has played an irreplaceable role in the CVN routine data processing, e.g., in the Chinese lunar exploration project. This correlator will be upgraded to process geodetic and astronomical observation data. In the future, with several new stations joining the network, CVN will carry out crustal movement observations, quick UT1 measurements, astrophysical observations, and deep space exploration activities. For the geodetic or astronomical observations, we need a wide-band 10-station correlator. For spacecraft tracking, a realtime and highly reliable correlator is essential. To meet the scientific and navigation requirements of CVN, two parallel software correlators in the multiprocessor environments are under development. A high speed, 10-station prototype correlator using the mixed Pthreads and MPI (Massage Passing Interface) parallel algorithm on a computer cluster platform is being developed. Another real-time software correlator for spacecraft tracking adopts the thread-parallel technology, and it runs on the SMP (Symmetric Multiple Processor) servers. Both correlators have the characteristic of flexible structure and scalability.

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

DTIC Science & Technology

2013-12-01

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...Ship (CVN 80) DAB Program Review -Platform-Level Integration D ... ....., Milestone C .. EMALS EMALS Delivery (with Ship) .-:o; IOC ..:<! IOT ...E IOT &E Start ..:<! IOT &E Complete -· Platform-Level Integration .. ...:<! CVN 78 Milestones SAR Baseline Dev Est Current APB Development

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.

Coordinated ultraviolet and radio observations of selected nearby stars

NASA Technical Reports Server (NTRS)

Lang, Kenneth R.

1987-01-01

All of the US2 shifts assigned were successfully completed with simultaneous International Ultraviolet Explorer (IUE) and the Very Large Array (VLA) observations of the proposed target stars. The target stars included dwarf M flare stars and RS CVn stars. The combined ultraviolet (IUE) and microwave (VLA) observations have provided important new insights to the radiation mechanisms at these two widely-separated regions of the electromagnetic spectrum. The VLA results included the discovery of narrow-band microwave radiation and rapid time variations in the microwave radiation of dwarf M flare stars. The results indicate that conventional radiation mechanisms cannot explain the microwave emission from these stars. In general, ultraviolet variations and bursts occur when no similar variations are detected at microwave wavelengths and vice versa. Although these is some overlap, the variations in these two spectral regions are usually uncorrelated, suggesting that there is little interaction between the activity centers at the two associated atmospheric levels.

Observational constraints on the inter-binary stellar flare hypothesis for the gamma-ray bursts

NASA Astrophysics Data System (ADS)

Rao, A. R.; Vahia, M. N.

1994-01-01

The Gamma Ray Observatory/Burst and Transient Source Experiment (GRO/BATSE) results on the Gamma Ray Bursts (GRBs) have given an internally consistent set of observations of about 260 GRBs which have been released for analysis by the BATSE team. Using this database we investigate our earlier suggestion (Vahia and Rao, 1988) that GRBs are inter-binary stellar flares from a group of objects classified as Magnetically Active Stellar Systems (MASS) which includes flare stars, RS CVn binaries and cataclysmic variables. We show that there exists an observationally consistent parameter space for the number density, scale height and flare luminosity of MASS which explains the complete log(N) - log(P) distribution of GRBs as also the observed isotropic distribution. We further use this model to predict anisotropy in the GRB distribution at intermediate luminosities. We make definite predictions under the stellar flare hypothesis that can be tested in the near future.

Butterfly Diagram and Activity Cycles in HR 1099

NASA Astrophysics Data System (ADS)

Berdyugina, Svetlana V.; Henry, Gregory W.

2007-04-01

We analyze photometric data of the active RS CVn-type star HR 1099 for the years 1975-2006 with an inversion technique and reveal the nature of two activity cycles of 15-16 yr and 5.3+/-0.1 yr duration. The 16 yr cycle is related to variations of the total spot area and is coupled with the differential rotation, while the 5.3 yr cycle is caused by the symmetric redistribution of the spotted area between the opposite stellar hemispheres (flip-flop cycle). We recover long-lived active regions comprising two active longitudes that migrate in the orbital reference frame with a variable rate because of the differential rotation along with changes in the mean spot latitudes. The migration pattern is periodic with the 16 yr cycle. Combining the longitudinal migration of the active regions with a previously measured differential rotation law, we recover the first stellar butterfly diagram without an assumption about spot shapes. We find that mean latitudes of active regions at opposite longitudes change antisymmetrically in the course of the 16 yr cycle: while one active region migrates to the pole, the other approaches the equator. This suggests a precession of the global magnetic field with respect to the stellar rotational axis.

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

DTIC Science & Technology

2015-12-17

AP funding for the ship. Oversight issues for Congress for the CVN-78 program include the following:  the potential impact on the CVN-78 program...Potential Impact of Continuing Resolution (CR) for FY2016 .................................................. 7 Overview...7 Impact on CVN-78 Program

MM Herculis - An eclipsing binary of the RS CVn

NASA Technical Reports Server (NTRS)

Sowell, J. R.; Hall, D. S.; Henry, G. W.; Burke, E. W., Jr.; Milone, E. F.

1983-01-01

V, B and U differential photoelectric photometry has been obtained for the RS Canum Venaticorum-class eclipsing binary star MM Her, with the light outside the eclipse being Fourier-analyzed to study wave migration and amplitude. These, together with the mean light level of the system, have been monitored from 1976 through 1980. Observations within the eclipse have revealed eclipses to be partial, rather than total as previously thought. The geometric elements of the presently rectified light curve are forced on the pre-1980 light curves and found to be compatible. With these elements, and previously obtained double line radial velocity curves, new absolute dimensions of 1.18 solar masses and 1.58 solar radii are calculated for the hotter star and 1.27 solar masses and 2.83 solar radii for the cooler star. The plotting of color indices on the color-color curve indicates G2V and K2IV spectral types.

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...Budget Defense Acquisition Management Information Retrieval (DAMIR) March 21, 2016 17:17:44 UNCLASSIFIED CVN 78 December 2015 SAR March 21, 2016 17...December 2015 SAR March 21, 2016 17:17:44 UNCLASSIFIED 3 PB - President’s Budget PE - Program Element PEO - Program Executive Officer PM - Program Manager

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

DTIC Science & Technology

2009-07-17

releaseid= 12600 . 2 The Navy has not identified which specific CVN it would transfer, and a CVN transferred to Mayport could come from any of the...available online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600 . 7Although the Navy states that the CVN based at Yokosuka is

The first Doppler images of the eclipsing binary SZ Piscium

NASA Astrophysics Data System (ADS)

Xiang, Yue; Gu, Shenghong; Cameron, A. Collier; Barnes, J. R.; Zhang, Liyun

2016-02-01

We present the first Doppler images of the active eclipsing binary system SZ Psc, based on the high-resolution spectral data sets obtained in 2004 November and 2006 September-December. The least-squares deconvolution technique was applied to derive high signal-to-noise profiles from the observed spectra of SZ Psc. Absorption features contributed by a third component of the system were detected in the LSD profiles at all observed phases. We estimated the mass and period of the third component to be about 0.9 M⊙ and 1283 ± 10 d, respectively. After removing the contribution of the third body from the least-squares deconvolved profiles, we derived the surface maps of SZ Psc. The resulting Doppler images indicate significant star-spot activities on the surface of the K subgiant component. The distributions of star-spots are more complex than that revealed by previous photometric studies. The cooler K component exhibited pronounced high-latitude spots as well as numerous low- and intermediate-latitude spot groups during the entire observing seasons, but did not show any large, stable polar cap, different from many other active RS CVn-type binaries.

The onset of chromospheric activity among the A and F stars

NASA Technical Reports Server (NTRS)

Simon, Theodore; Landsman, Wayne

1991-01-01

Results are reported from a search for an upper boundary for the onset of main-sequence star activity based on a quest for high-temperature UV line emission in a large collection of IUE spectra. It is shown that strong chromospheric emission is common among early F dwarf and subgiant stars. At its brightest, the emission is equal to that of the most active solar-type stars and is exceeded only by that of the spotted RS CVn and BY Dra variables. It is suggested that the emission from the main-sequence stars reaches a peak near B-V = 0.28, in the vicinity of spectral type F0 V, before it declines to lower flux levels among the late A stars. Emission is seen in some dwarf stars as early as B-V = 0.25. It is demonstrated that the C II emission of stars earlier than the spectral type F5 is uncorrelated with rotation. Previous findings that the coronal X-ray:chromospheric UV flux ratio is lower for stars earlier than spectral type F5 than for those later than F5 are confirmed.

Long-term magnetic activity in close binary systems. I. Patterns of color variations

NASA Astrophysics Data System (ADS)

Messina, S.

2008-03-01

Aims:This is the first of a series of papers in which we present the results of a long-term photometric monitoring project carried out at Catania Astrophysical Observatory aimed at studying magnetic activity in late-type components of close binary systems, its dependence on global stellar parameters, and its evolution on different time scales from days to years. In this first paper, we present the complete observation dataset and new results of an investigation into the origin of brightness and color variations observed in the well-known magnetically active close binary stars: AR Psc, VY Ari, UX Ari, V711 Tau, EI Eri, V1149 Ori, DH Leo, HU Vir, RS CVn, V775 Her, AR Lac, SZ Psc, II Peg and BY Dra Methods: About 38 000 high-precision photoelectric nightly observations in the U, B and V filters are analysed. Correlation and regression analyses of the V magnitude vs. U-B and B-V color variations are carried out and a comparison with model variations for a grid of active region temperature and filling factor values is also performed. Results: We find the existence of two different patterns of color variation. Eight stars in our sample: BY Dra, VY Ari, V775 Her, II Peg, V1149 Ori, HU Vir, EI Eri and DH Leo become redder when they become fainter, as is expected from the presence of active regions consisting of cool spots. The other six stars show the opposite behaviour, i.e. they become bluer when they become fainter. For V711 Tau this behaviour could be explained by the increased relative U- and B-flux contribution by the earlier-type component of the binary system when the cooler component becomes fainter. On the other hand, for AR Psc, UX Ari, RS CVn, SZ Psc and AR Lac the existence of hot photospheric faculae must be invoked. We also found that in single-lined and double-lined binary stars in which the fainter component is inactive or much less active the V magnitude is correlated to B-V and U-B color variations in more than 60% of observation seasons. The correlation is found in less than 40% of observation seasons when the fainter component has a non-negligible level of activity and/or hot faculae are present but they are either spatially or temporally uncorrelated to spots. I dedicate this paper to the memory of the P.I. of this project, Prof. Marcello Rodonò, who suddenly passed away on October 23, 2005. To him my sincere estimation and deepest gratitude. Based on observations collected at INAF-Catania Astrophysical Observatory, Italy.

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

DTIC Science & Technology

2009-12-23

releaseid= 12600 . 2 The Navy has not identified which specific CVN it would transfer, and a CVN transferred to Mayport could come from any of the...Mayport,” available online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600 . 7Although the Navy states that the CVN based at Yokosuka

The OGLE Collection of Variable Stars. Over 450 000 Eclipsing and Ellipsoidal Binary Systems Toward the Galactic Bulge

NASA Astrophysics Data System (ADS)

Soszyński, I.; Pawlak, M.; Pietrukowicz, P.; Udalski, A.; Szymański, M. K.; Wyrzykowski, Ł.; Ulaczyk, K.; Poleski, R.; Kozłowski, S.; Skowron, D. M.; Skowron, J.; Mróz, P.; Hamanowicz, A.

2016-12-01

We present a collection of 450 598 eclipsing and ellipsoidal binary systems detected in the OGLE fields toward the Galactic bulge. The collection consists of binary systems of all types: detached, semi-detached, and contact eclipsing binaries, RS CVn stars, cataclysmic variables, HW Vir binaries, double periodic variables, and even planetary transits. For all stars we provide the I- and V-band time-series photometry obtained during the OGLE-II, OGLE-III, and OGLE-IV surveys. We discuss methods used to identify binary systems in the OGLE data and present several objects of particular interest.

Orbital variability in the eclipsing pulsar binary PSR B1957+20

NASA Technical Reports Server (NTRS)

Arzoumanian, Z.; Fruchter, A. S.; Taylor, J. H.

1994-01-01

We have conducted timing observations of the eclipsing millisecond binary pulsar PSR B1957+20, extending the span of data on this pulsar to more than five years. During this time the orbital period of the system has varied by roughly Delta P(sub b)/P(sub b) = 1.6 x 10(exp -7), changing quardratically with time and displaying with time and displaying an orbital period second derivative of P(sub b) = (1.43 +/- 0.08) x 10(exp -18)/sec. The previous measurement of a large negative orbital period derivative reflected only the short-term behavior of the system during the early observations; the orbital period derivative is now positive. If, as we suspect, the PSR B1957+20 system is undergoing quasi-cyclic orbital period variations similar to those found in other close binaries such as Algol and RS CVn, then the 0.025 solar mass companion to PSR B1957+20 is most likely non-degenerate, convective, and magnetically active.

IUE observations of pre-main-sequence stars. I - Mg II and Ca II resonance line fluxes for T Tauri stars

NASA Technical Reports Server (NTRS)

Giampapa n, M. S.

1981-01-01

IUE satellite and Lick 3 m reflector image tube scanner measurements of the Mg II and Ca II resonance lines in a sample of T Tauri stars are the basis of a discussion of the Mg II h and k line emission and the Ca II H and K line emission, within the context of stellar chromospheres. Corroborative evidence is presented for the chromospheric origin of these resonance lines, and chromospheric radiative loss rates in the Mg II and Ca II resonance lines are derived. It is found that the degree of nonradiative heating present in the outer atmospheres of T Tauri stars generally exceeds that of the RS CVn systems, as well as the dMe stars and other active chromospheric dwarfs, and it is inferred that the surfaces of such pre-main sequence stars are covered by regions similar to solar plages. The mean chromospheric electron density of T Tauri stars is determined as 10 to the 11th/cu cm.

Restricted HIV-1 Env glycan engagement by lectin-reengineered DAVEI protein chimera is sufficient for lytic inactivation of the virus

PubMed Central

Parajuli, Bibek; Acharya, Kriti; Bach, Harry C.; Parajuli, Bijay; Zhang, Shiyu; Smith, Amos B.; Abrams, Cameron F.; Chaiken, Irwin

2018-01-01

We previously reported a first-generation recombinant DAVEI construct, a dual action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane proximal external region or its derivative peptide Trp3. DAVEI exhibits potent and irreversible inactivation of HIV-1 (human immunodeficiency virus) viruses by dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate with multiple glycosylation sites in gp120 and its multivalency limit current understanding of the molecular arrangement of the DAVEI molecules on trimeric spike. Here, we constructed and investigated the virolytic function of second-generation DAVEI molecules using a simpler lectin, microvirin (MVN). MVN is a monovalent lectin with a single glycan-binding site in gp120, is structurally similar to CVN and exhibits no toxicity or mitogenicity, both of which are liabilities with CVN. We found that, like CVN-DAVEI-L2-3Trp (peptide sequence DKWASLWNW), MVN-DAVEI2-3Trp exploits a similar mechanism of action for inducing HIV-1 lytic inactivation, but by more selective gp120 glycan engagement. By sequence redesign, we significantly increased the potency of MVN-DAVEI2-3Trp protein. Unlike CVN-DAVEI2-3Trp, re-engineered MVN-DAVEI2-3Trp(Q81K/M83R) virolytic activity and its interaction with gp120 were both competed by 2G12 antibody. That the lectin domain in DAVEIs can utilize MVN without loss of virolytic function argues that restricted HIV-1 Env (envelope glycoprotein) glycan engagement is sufficient for virolysis. It also shows that DAVEI lectin multivalent binding with gp120 is not required for virolysis. MVN-DAVEI2-3Trp(Q81K/M83R) provides an improved tool to elucidate productive molecular arrangements of Env-DAVEI enabling virolysis and also opens the way to form DAVEI fusions made up of gp120-binding small molecules linked to Trp3 peptide. PMID:29343613

Rational and Computational Design of Stabilized Variants of Cyanovirin-N which Retain Affinity and Specificity for Glycan Ligands

PubMed Central

Patsalo, Vadim; Raleigh, Daniel P.; Green, David F.

2011-01-01

Cyanovirin-N (CVN) is an 11-kDa pseudo-symmetric cyanobacterial lectin that has been shown to inhibit infection by the Human Immunodeficiency Virus (HIV) by binding to high-mannose oligosaccharides on the surface of the viral envelope glycoprotein gp120. In this work we describe rationally-designed CVN variants that stabilize the protein fold while maintaining high affinity and selectivity for their glycan targets. Poisson–Boltzmann calculations and protein repacking algorithms were used to select stabilizing mutations in the protein core. By substituting the buried polar side chains of Ser11, Ser20, and Thr61 with aliphatic groups, we stabilized CVN by nearly 12 °C against thermal denaturation, and by 1 m of GuaHCl against chemical denaturation, relative to a previously-characterized stabilized mutant. Glycan microarray binding experiments confirmed that the specificity profile of carbohydrate binding is unperturbed by the mutations, and is identical for all variants. In particular, the variants selectively bound glycans containing the Manα(1→2)Man linkage, which is the known minimal binding unit of CVN. We also report the slow denaturation kinetics of CVN and show that they can complicate thermodynamic analysis; in particular, the unfolding of CVN cannot be described as a fixed two-state transition. Accurate thermodynamic parameters are needed to describe the complicated free energy landscape of CVN, and we provide updated values for CVN unfolding. PMID:22032696

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

DTIC Science & Technology

2009-09-23

at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600 . 2 The Navy has not identified which specific CVN it would transfer, and a CVN...Determine Aircraft Carrier Homeporting In Mayport,” available online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600 . 7Although

Cooperative Vehicular Networking: A Survey

PubMed Central

Ahmed, Ejaz

2018-01-01

With the remarkable progress of cooperative communication technology in recent years, its transformation to vehicular networking is gaining momentum. Such a transformation has brought a new research challenge in facing the realization of cooperative vehicular networking (CVN). This paper presents a comprehensive survey of recent advances in the field of CVN. We cover important aspects of CVN research, including physical, medium access control, and routing protocols, as well as link scheduling and security. We also classify these research efforts in a taxonomy of cooperative vehicular networks. A set of key requirements for realizing the vision of cooperative vehicular networks is then identified and discussed. We also discuss open research challenges in enabling CVN. Lastly, the paper concludes by highlighting key points of research and future directions in the domain of CVN. PMID:29881331

Crystal molecular dynamics simulations to speed up MM/PB(GB)SA evaluation of binding free energies of di-mannose deoxy analogs with P51G-m4-Cyanovirin-N.

PubMed

Vorontsov, Ivan I; Miyashita, Osamu

2011-04-30

Complexes of two Cyanovirin-N (CVN) mutants, m4-CVN and P51G-m4-CVN, with deoxy di-mannose analogs were employed as models to generate conformational ensembles using explicit water Molecular Dynamics (MD) simulations in solution and in crystal environment. The results were utilized for evaluation of binding free energies with the molecular mechanics Poisson-Boltzmann (or Generalized Born) surface area, MM/PB(GB)SA, methods. The calculations provided the ranking of deoxy di-mannose ligands affinity in agreement with available qualitative experimental evidences. This confirms the importance of the hydrogen-bond network between di-mannose 3'- and 4'-hydroxyl groups and the protein binding site B(M) as a basis of the CVN activity as an effective HIV fusion inhibitor. Comparison of binding free energies averaged over snapshots from the solution and crystal simulations showed high promises in the use of the crystal matrix for acceleration of the conformational ensemble generation, the most time consuming step in MM/PB(GB)SA approach. Correlation between energy values based on solution versus crystal ensembles is 0.95 for both MM/PBSA and MM/GBSA methods. Copyright © 2010 Wiley Periodicals, Inc.

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

DTIC Science & Technology

2009-06-19

available online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600 . 2 The Navy has not identified which specific CVN it would...releaseid= 12600 . 7Although the Navy states that the CVN based at Yokosuka is forward deployed to Yokosuka, the ship is commonly referred to as being

HM Sagittae - Symbiotic cousin of the RS CVn stars

NASA Technical Reports Server (NTRS)

Blair, W. P.; Stencel, R. E.; Feibelman, W. A.; Shaviv, G.

1981-01-01

In the brief time since its brightening in 1975, the optical spectrum of HM Sagittae has shown considerable variation in both its general characteristics and relative line intensity ratios. The observations place HM Sagittae in a small class of objects which are thought to be proto-planetary nebulae, of which V 1016 Cygni is the prototype. Attention is given to derived density and temperature, helium abundance and nebular mass, and an evolutionary scenario. The considered observations show a decrease in the intensity of the continuum and a continuation of the trend toward higher excitation in the spectrum of HM Sagittae. Parallels are seen in the development of this object and V 1016 Cygni, with the implication that the trend toward higher excitation is expected to continue.

Catalogue of Main Characteristics of Pulsations of 173 Semi-Regular Stars

NASA Astrophysics Data System (ADS)

Chinarova, L. L.; Andronov, I. L.

2000-12-01

The characteristics of brightness variations of 173 semi-regular stars are tabulated: the moments and brightness of the extrema; the effective periods, amplitudes and significance obtained by using different methods: a) the periodogram analysis (harmonic least squares t) with prewhitening to determine characteristics and significance of waves with 3 periods; b) the wavelet analysis to determine characteristics of statistically significant waves; ) the "running parabola" scalegram analysis to determine the optimal filter half - width for smoothing. The characteristics may be used for more precise classification of semi-regular variables. Characteristics of the 6509 extrema of 147 stars are listed. The electronic version is available via http://ila.webjump.om. The observations for the analysis have been taken from the AFOEV and VSOLJ databases (with a duration up to 94 years) for the stars: AQ, EH, EK, RS, RU, RV, ST, TV, TY, TZ, UX, VX And; GY, PX, S, V, V844 Aql; V, Z Aqr; T Ari; AG, RS, S, UU, Z Aur; RV, RW, RX, RZ, U, V, WY Boo; T Cae; RR, RS, RY, S, ST, U Cam; RT Cap; PZ, SV, UX, V393, V465, WZ Cas; T, Y Cen; AR, RU, RW, RX, SS, TY, W Cep; T Cet; RS, RT, T, X Cnc; RR, RS, TT CrB; V, Y Cvn; AA, AF, AI, AV, AW, BC, RS, RU, RV, RW, RZ, TT, V460, W Cyg; EU, U Del; RS, RY, S, TX, UX, WZ Dra; SY, Z Eri; IS, NQ, RS, SW, TU, TV, Y Gem; DE, MZ, RR, ST, SX, UU, X Her; FF, RT, U, V, W, Y Hya; RS Lac; RY, SX Leo; RX, S Lep; U, W LMi; Y, EG, R, SZ Lyr; RV, SW, X Mon; V759 Oph; BQ, FX, GT, RT, W Ori; AF, AK, SV, TX Peg; AD, BU, DY, FZ, RS, RU, S, SU, SY, T, UZ, W, XX Per; R Pic; RT, RW, Z Psc; BM Sco; S Sct; FG Ser; X Sge; AB, TT, W, Y Tau; W Tri; RX, RY, RZ, ST,SV, V, Y, Z UMa; R, V UMi; RT, SS, SW Vir; RU Vul.

Chemical Compositions and Abundance Anomalies in Stellar Coronae ADP 99

NASA Technical Reports Server (NTRS)

Oliversen, Ronald J. (Technical Monitor); Drake, Jeremy

2004-01-01

New atomic data for tackling some of our spectra have been investigated by co-I Laming (NRL), including the effects of recombination on spectral line fluxes that are not included in, for example, the CHIANTI database models. Promising new progress has been made with modelling some of the recent abundance anomaly results in terms of Alven wave-driven separation of neutrals and ions in the upper chromosphere. The problems that existing models have is that they cannot simultaneously explain the low-FIP enhanced solar-like coronae and the high-FIP rich active coronae of RS CVn-like stars. The Alven wave model shows promise with both of these scenarios, with the fractionation or suppression of low-FIP ions depending on the characteristics of the chromosphere. This work is currently in the writing up stage. In summary, the work to-date is making good progress in mapping abundance anomalies as a function of spectral type and activity level. We are also making good progress with modelling that we will be able to test with our observational results. With one more year of effort, we'anticipate that the bulk of the work described above can be published, together with outstanding key studies on anomalies among the different active binaries.

The Spotted Active Binary UX Arietis

NASA Astrophysics Data System (ADS)

Hummel, Christian

2018-04-01

UX Arietis is one of the most active members of the RS CVn class of binaries in which spin-up of a sub-giant/giant star by a close companion led to the creation of magnetic fields which in turn are responsible for the radio and X-ray flares of UX Ariestis as well as its photometric variability. We observed this binary with the MIRC beam combiner at the CHARA array and made images of a single large spot rotating in and out of view over a month in 2012. A precise orbit was derived using the Wilson-Devinney code to account for the effect of the spot on the measured visibilities. Archival and new radial velocities taken at the NOT were also corrected for spot activity and allowed us to determine precise stellar masses and luminosities for the components. Consistency with the predicted locations in the HR-diagram is achieved after a careful analysis of the effect of spots. The orbit can be used to establish the relative locations of the stellar components at times when radio observations by Ros and Massi (2007) with the VLBA detected two radio components moving around each other. We tentatively conclude that radio emission in UX Arietis flows along magnetic flux tubes between the stars.

The recent progress of Chinese VLBI Network

NASA Astrophysics Data System (ADS)

Zheng, Weimin

2015-08-01

At present, Chinese VLBI Network (CVN) consists of 5 antennas (Seshan 25m, Urumqi 25m, Kunming 30m, Miyun 50m and Tianma 65m) and one data processing center in Shanghai Observatory, Chinese academy of sciences. It is a synthetic aperture radio telescope with the equivalent diameter up to 3000 Km. Through e-VLBI (electronic VLBI) technology, CVN is connected by the commuication network. It is a multi-purpose scientific research platform radio for geodesy, astronomy, as well as deep space exploration. In Geodesy, CVN is the component of the Crustal Movement Observation Network of China. Since the year of 2006, more than 20 geodetic domestic observations have been carried out. A set of phase-referencing observations of pulsars with CVN has carried out and got preliminary results. CVN also joined the Chinese lunar exploration Project from 2007 and supported 4 Chang’E series lunar probe missions. In Chang’E-3 mission, using the in-beam VLBI observations, the relative position accuracy of Rover and Lander is up to 1 meter.In recent years, we have updated the facilities of CVN from antenna, receivers, VLBI terminals to correlator. Participation of Tianma 65m antennas increases its performance. In 2012, Shanghai correlator was accepted as the IVS correlator. After upgrade, Shanghai correlator will try to provide the data process service for IVS community from 2015. To drive the construction of the planned VGOS (VLBI2010 Global Observing System) station, at least two VOGS 13m antenna will join CVN in the near future. Construction of the first VOGS antenna in Shanghai hopes to begin this year.The new VLBI correlator and digital terminal are under development. From participation in VGOS, we plan to study the earth rotation especially of high frequency and corresponding geophysical signals, to link China’s regional reference frame to ITRF, and etc. CVN is willing to join the research corporation with IVS, EVN, VLBA and AOV (Asia- Oceania VLBI Group for Geodesy and Astrometry) in the future.

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

DTIC Science & Technology

2013-10-22

states: The CVN 78 is experiencing cost growth due to “first of class” material availability (i.e., valves, actuators ), construction labor...assessment during IOT &E [initial operational test and evaluation]. • The current TEMP [test and evaluation master plan] does not adequately address...developmental testing significantly raises the likelihood of the discovery of platform-level problems during IOT &E. • The Navy plans to deliver CVN-78 in

High-speed photometry of Gaia14aae: an eclipsing AM CVn that challenges formation models

NASA Astrophysics Data System (ADS)

Green, M. J.; Marsh, T. R.; Steeghs, D. T. H.; Kupfer, T.; Ashley, R. P.; Bloemen, S.; Breedt, E.; Campbell, H. C.; Chakpor, A.; Copperwheat, C. M.; Dhillon, V. S.; Hallinan, G.; Hardy, L. K.; Hermes, J. J.; Kerry, P.; Littlefair, S. P.; Milburn, J.; Parsons, S. G.; Prasert, N.; van Roestel, J.; Sahman, D. I.; Singh, N.

2018-05-01

AM CVn-type systems are ultracompact, hydrogen-deficient accreting binaries with degenerate or semidegenerate donors. The evolutionary history of these systems can be explored by constraining the properties of their donor stars. We present high-speed photometry of Gaia14aae, an AM CVn with a binary period of 49. 7 min and the first AM CVn in which the central white dwarf is fully eclipsed by the donor star. Modelling of the light curves of this system allows for the most precise measurement to date of the donor mass of an AM CVn, and relies only on geometric and well-tested physical assumptions. We find a mass ratio q = M2/M1 = 0.0287 ± 0.0020 and masses M1 = 0.87 ± 0.02 M⊙ and M2 = 0.0250 ± 0.0013 M⊙. We compare these properties to the three proposed channels for AM CVn formation. Our measured donor mass and radius do not fit with the contraction that is predicted for AM CVn donors descended from white dwarfs or helium stars at long orbital periods. The donor properties we measure fall in a region of parameter space in which systems evolved from hydrogen-dominated cataclysmic variables are expected, but such systems should show spectroscopic hydrogen, which is not seen in Gaia14aae. The evolutionary history of this system is therefore not clear. We consider a helium-burning star or an evolved cataclysmic variable to be the most likely progenitors, but both models require additional processes and/or fine-tuning to fit the data. Additionally, we calculate an updated ephemeris which corrects for an anomalous time measurement in the previously published ephemeris.

Rhizosecretion improves the production of Cyanovirin-N in Nicotiana tabacum through simplified downstream processing.

PubMed

Madeira, Luisa M; Szeto, Tim H; Ma, Julian K-C; Drake, Pascal M W

2016-07-01

Rhizosecretion has many advantages for the production of recombinant pharmaceuticals, notably facile downstream processing from hydroponic medium. The aim of this study was to increase yields of the HIV microbicide candidate, Cyanovirin-N (CV-N), obtained using this production platform and to develop a simplified methodology for its downstream processing from hydroponic medium. Placing hydroponic cultures on an orbital shaker more than doubled the concentration of CV-N in the hydroponic medium compared to plants which remained stationary, reaching a maximum of approximately 20μg/ml in one week, which is more than 3 times higher than previously reported yields. The protein composition of the hydroponic medium, the rhizosecretome, was characterised in plants cultured with or without the plant growth regulator alpha-napthaleneacetic acid by LC-ESI-MS/MS, and CV-N was the most abundant protein. The issue of large volumes in the rhizosecretion system was addressed by using ion exchange chromatography to concentrate CV-N and partially remove impurities. The semi-purified CV-N was demonstrated to bind to HIV gp120 in an ELISA and to neutralise HIVBa-L with an IC50 of 6nM in a cell-based assay. Rhizosecretion is therefore a practicable and inexpensive method for the production of functional CV-N. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fermi/LAT detection of a transient gamma-ray flare in the vicinity of the binary star DG CVn

DOE PAGES

Loh, Alan; Corbel, Stéphane; Dubus, Guillaume

2017-02-16

Solar flares are regularly detected by the Large Area Telescope (LAT) on board the Fermi satellite, however no γ-ray emission from other stellar eruptions has ever been captured. The Swift detection in 2014 April of a powerful outburst originating from DG CVn, with associated optical and radio emissions, enticed us to search for possible 0.1–100 GeV emission from this flaring nearby binary star using the Fermi/LAT. No γ-ray emission is detected from DG CVn in 2014, but we report a significant γ-ray excess in 2012 November, at a position consistent with that of the binary. There are no reports ofmore » contemporary flaring at other wavelengths from DG CVn or any other source within the error circle of the γ-ray source. As a result, we argue that the γ-ray flare is more likely to have been associated with a background blazar than with DG CVn and identify a candidate for follow-up study.« less

An Intense Polarized Radio Flare from AR Lac

NASA Astrophysics Data System (ADS)

Mutel, R. L.; Neff, J. E.; Bookbinder, J.; Pagano, I.

1992-12-01

We have detected an intense, highly circularly polarized radio flare from the close binary system AR Lacertae during a 4 day multi-wavelength observing campaign in 1991 December. The flare lasted more than 6 hours and was preceded by a strong CIV flare one day earlier. The peak circular polarization was 70%, 38%,and 39% RCP at 1.4, 4.9, and 8.4 GHz respectively, with ~ 15% LCP at 15 and 22 GHZ. The high degree of circular polarization over such a large time scale and frequency range is highly unusual compared with previously observed radio flares from RS CVn binaries. Given these unusual characteristics, it is difficult to interpret the radiation mechanism either as a result of gyrosynchrotron emission or a coherent process such as an electron cyclotron maser.

Copernicus observations of neutral hydrogen and deuterium in the direction of HR 1099

NASA Technical Reports Server (NTRS)

Anderson, R. C.; Weiler, E. J.

1979-01-01

High-resolution Copernicus U1 scans were obtained of the bright RS CVn binary HR 1099 (d = 33 pc, galactic longitude = 185 deg, galactic latitude = -41 deg) in October 1977. Strong emission at L-alpha was detected. The interstellar L-alpha absorption features of H I and D I were also observed. Analyses of these interstellar lines are reported in this paper. The average density of neutral H in the direction of this system is found to be 0.006-0.012 per cu cm, which, because the local density is higher, requires a marked inhomogeneity along this line of sight. This result, when combined with other recent studies of the local interstellar medium, suggests the sun is located within a moderate-density H I region.

PTF1 J191905.19+481506.2—A partially eclipsing AM CVn system discovered in the Palomar transient factory

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

Levitan, David; Groot, Paul J.; Prince, Thomas A.

2014-04-20

We report on PTF1 J191905.19+481506.2, a newly discovered, partially eclipsing, outbursting AM CVn system found in the Palomar Transient Factory synoptic survey. This is only the second known eclipsing AM CVn system. We use high-speed photometric observations and phase-resolved spectroscopy to establish an orbital period of 22.4559(3) minutes. We also present a long-term light curve and report on the normal and super-outbursts regularly seen in this system, including a super-outburst recurrence time of 36.8(4) days. We use the presence of the eclipse to place upper and lower limits on the inclination of the system and discuss the number of knownmore » eclipsing AM CVn systems versus what would be expected.« less

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.

Z CVn - Still mysterious

NASA Astrophysics Data System (ADS)

Skarka, M.; Liška, J.; Dřevěný, R.; Sódor, Á.; Barnes, T.; Kolenberg, K.

2018-04-01

We comment on short- and long-term pulsation period variations of Z CVn, a classical RR Lyrae star with the Blazhko effect. Z CVn shows cyclic-like O-C diagram that can be interpreted as a consequence of binarity throught the light travel time effect. We show that this hypothesis is false and that the observed long-term period variations must be caused by some effect that is intrinsic to the star. We also show that the Blazhko period is not simply anti-correlated with the long-term period variations as was suggested by previous authors.

Chemical Compositions and Abundance Anomalies in Stellar Coronae ADP 99

NASA Technical Reports Server (NTRS)

Drake, Jeremy; Oliversen, Ronald J. (Technical Monitor)

2003-01-01

Progress has been made using both EUVE (Extreme Ultraviolet Explorer) and ASCA (Advanced Satellite for Cosmology and Astrophysics) data and a new postdoctoral scientist has now been hired. Stars studied to date include YY Gem (dMe binary), xi Boo A (intermediate activity G8 V), xi UMa (more active G quadruple system) HR1099 (K1 IV + G5 V) RS CVn-like, AU Mic (dMe). In addition to a paper that concentrated on abundancies in HR1099, a paper was recently submitted on the coronal abundances of AR(tilde)Lac that revealed an interesting pattern of overabundances of very low FIP elements (Al and Ca) compared to the low FIP elements Si, Mg and Fe. Two papers are nearing completion on methods of analysis and on the abundances in the corona of AU(tilde)Mic. Additionally, two invited conference proceedings papers are being published on this work. The main conclusion of the study to date is that our existing ideas of coronal abundance anomalies need complete revision. The solar-like FIP effect is replaced by a pattern than appears to enhance high FIP elements rather than low FIP elements in very active stars. The archival studies we are undertaking now are revealing some key details of these patterns, and are beginning to map out the anomalies as a function of spectral type, a key goal of this study.

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.

Evolutionary orbital period change in BH Virginis

NASA Astrophysics Data System (ADS)

Gebrehiwot, Y. M.; Tessema, S. B.; Berdnikov, L. N.

2017-04-01

The study of orbital period change of close binaries, such as BH Virginis (BH Vir), using very long time baseline is vital to understand evolutionary processes of the system. In this paper, we use photometric data to analyze the evolutionary orbital period change of the short period RS CVn-type binary system, BH Vir, with a time baseline spanning 123 years. We used the software version of the Hertzsprung method to describe the O-C curve of the system, and we found that the orbital period secularly decreases at a rate of dp/dt=-(0.0013000 ± 0.0000863) s yr^{-1}. Because BH Vir is a typical detached binary system and both components are late type (G0 V + G2 V) stars, the evolutionary period change could be caused by the angular momentum loss due to tides coupled with magnetic breaking.

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.

A cautionary tale of interpreting O-C diagrams: period instability in a classical RR Lyr Star Z CVn mimicking as a distant companion

NASA Astrophysics Data System (ADS)

Skarka, M.; Liška, J.; Dřevěný, R.; Guggenberger, E.; Sódor, Á.; Barnes, T. G.; Kolenberg, K.

2018-02-01

We present a comprehensive study of Z CVn, an RR Lyrae star that shows long-term cyclic variations of its pulsation period. A possible explanation suggested from the shape of the O-C diagram is the light travel-time effect, which we thoroughly examine. We used original photometric and spectroscopic measurements and investigated the period evolution using available maximum times spanning more than one century. If the binary hypothesis is valid, Z CVn orbits around a black hole with minimal mass of 56.5 M_{⊙} on a very wide (Porbit = 78.3 yr) and eccentric orbit (e = 0.63). We discuss the probability of the formation of a black hole-RR Lyrae pair, and, although we found it possible, there is no observational evidence of the black hole in the direction to Z CVn. However, the main objection against the binary hypothesis is the comparison of the systemic radial velocity curve model and spectroscopic observations that clearly show that Z CVn cannot be bound in such a binary. Therefore, the variations of pulsation period are likely intrinsic to the star. This finding represents a discovery/confirmation of a new type of cyclic period changes in RR Lyrae stars. By the analysis of our photometric data, we found that the Blazhko modulation with period of 22.931 d is strongly dominant in amplitude. The strength of the phase modulation varies and is currently almost undetectable. We also estimated photometric physical parameters of Z CVn and investigated their variations during the Blazhko cycle using the inverse Baade-Wesselink method.

Masked syllable priming effects in word and picture naming in Chinese.

PubMed

You, Wenping; Zhang, Qingfang; Verdonschot, Rinus G

2012-01-01

Four experiments investigated the role of the syllable in Chinese spoken word production. Chen, Chen and Ferrand (2003) reported a syllable priming effect when primes and targets shared the first syllable using a masked priming paradigm in Chinese. Our Experiment 1 was a direct replication of Chen et al.'s (2003) Experiment 3 employing CV (e.g., ,/ba2.ying2/, strike camp) and CVG (e.g., ,/bai2.shou3/, white haired) syllable types. Experiment 2 tested the syllable priming effect using different syllable types: e.g., CV (,/qi4.qiu2/, balloon) and CVN (,/qing1.ting2/, dragonfly). Experiment 3 investigated this issue further using line drawings of common objects as targets that were preceded either by a CV (e.g., ,/qi3/, attempt), or a CVN (e.g., ,/qing2/, affection) prime. Experiment 4 further examined the priming effect by a comparison between CV or CVN priming and an unrelated priming condition using CV-NX (e.g., ,/mi2.ni3/, mini) and CVN-CX (e.g., ,/min2.ju1/, dwellings) as target words. These four experiments consistently found that CV targets were named faster when preceded by CV primes than when they were preceded by CVG, CVN or unrelated primes, whereas CVG or CVN targets showed the reverse pattern. These results indicate that the priming effect critically depends on the match between the structure of the prime and that of the first syllable of the target. The effect obtained in this study was consistent across different stimuli and different tasks (word and picture naming), and provides more conclusive and consistent data regarding the role of the syllable in Chinese speech production.

A Multiplicity Survey of Chromospherically Active and Inactive Stars

NASA Technical Reports Server (NTRS)

Mason, Brian D.; Henry, Todd J.; Hartkopf, William I.; TenBrummelaar, Theo; Soderblom, David R.

1998-01-01

Surveys of the three samples of solar-type stars, segregated by chromospheric emission level, were made to determine their multiplicity fractions and to investigate the evolution of multiplicity with age. In total, 245 stars were searched for companions with DeltaV <= 3.0 and separations of 0.035" to 1.08" using optical speckle interferometry, By incorporating the visual micrometer survey for duplicity of the LamontHussey Observatory, the angular coverage was extended to 5.0" with no change in in the DeltaV limit. This magnitude difference allows mass ratios of 0.63 and larger to be detected throughout a search region of 2-127 AU for the stars observed. The 84 primaries observed in the chromospherically active sample are presumably part of a young population and are found to have a multiplicity fraction of 17.9% +/- 4.6%. The sample of 118 inactive, presumably older, primaries were selected and observed using identical methods and are found to have a multiplicity fraction of only 8.5% +/- 2.7%. Given the known link between chromospheric activity and age, these results tentatively imply a decreasing stellar multiplicity fraction from 1 to 4 Gyr, the approximate ages of the two samples. Finally, only two of the 14 very active primaries observed were found to have a companion meeting the survey detection parameters. In this case, many of the systems are either very young, or close, RS CVn type multiples that are unresolvable using techniques employed here.

Einstein Observatory coronal temperatures of late-type stars

NASA Technical Reports Server (NTRS)

Schmitt, J. H. M. M.; Collura, A.; Sciortino, S.; Vaiana, G. S.; Harnden, F. R., Jr.

1990-01-01

The results are presented of a survey of the coronal temperatures of late-type stars using the Einstein Observatory IPC. The spectral analysis shows that the frequently found one- and two-temperature descriptions are mainly influenced by the SNR of the data and that models using continuous emission measure distributions can provide equally adequate and physically more meaningful and more plausible descriptions. Intrinsic differences in differential emission measure distributions are found for four groups of stars. M dwarfs generally show evidence for high-temperature gas in conjunction with lower-temperature material, while main-sequence stars of types F and G have the high-temperature component either absent or very weak. Very hot coronae without the lower-temperature component appearing in dwarf stars are evident in most of the giant stars studied. RS CVn systems show evidence for extremely hot coronae, sometimes with no accompanying lower-temperature material.

Einstein Observatory magnitude-limited X-ray survey of late-type giant and supergiant stars

NASA Technical Reports Server (NTRS)

Maggio, A.; Vaiana, G. S.; Haisch, B. M.; Stern, R. A.; Bookbinder, J.

1990-01-01

Results are presented of an extensive X-ray survey of 380 giant and supergiant stars of spectral types from F to M, carried out with the Einstein Observatory. It was found that the observed F giants or subgiants (slightly evolved stars with a mass M less than about 2 solar masses) are X-ray emitters at the same level of main-sequence stars of similar spectral type. The G giants show a range of emissions more than 3 orders of magnitude wide; some single G giants exist with X-ray luminosities comparable to RS CVn systems, while some nearby large G giants have upper limits on the X-ray emission below typical solar values. The K giants have an observed X-ray emission level significantly lower than F and F giants. None of the 29 M giants were detected, except for one spectroscopic binary.

Einstein observations of selected close binaries and shell stars

NASA Technical Reports Server (NTRS)

Guinan, E. F.; Koch, R. H.; Plavec, M. J.

1984-01-01

Several evolved close binaries and shell stars were observed with the IPC aboard the HEAO 2 Einstein Observatory. No eclipsing target was detected, and only two of the shell binaries were detected. It is argued that there is no substantial difference in L(X) for eclipsing and non-eclipsing binaries. The close binary and shell star CX Dra was detected as a moderately strong source, and the best interpretation is that the X-ray flux arises primarily from the corona of the cool member of the binary at about the level of Algol-like or RS CVn-type sources. The residual visible-band light curve of this binary has been modeled so as to conform as well as possible with this interpretation. HD 51480 was detected as a weak source. Substantial background information from IUE and ground scanner measurements are given for this binary. The positions and flux values of several accidentally detected sources are given.

Copernicus observations of interstellar matter in the direction of HR 1099

NASA Technical Reports Server (NTRS)

Anderson, R. C.; Weiler, E. J.

1978-01-01

Results are reported for high-resolution Copernicus U1 and V2 scans of the bright RS CVn spectroscopic binary HR 1099. The observations reveal strong UV emission lines at L-alpha and Mg II h and k from the stars as well as interstellar H I and D I L-alpha absorption lines and interstellar Mg II h and k absorption in the direction of the binary system. Column densities, bulk velocities, and temperatures are derived for the interstellar features. A comparison of the derived number density of interstellar H I with data for the nearby star Epsilon Eri indicates an inhomogeneous distribution of interstellar hydrogen along the line of sight. The range of values obtained for the D/H ratio is shown to be consistent with results of other studies. A depletion factor of at least 5 with respect to the solar abundance is estimated for the interstellar magnesium.

A NEW TWIST IN THE EVOLUTION OF LOW-MASS STARS

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

Denissenkov, Pavel A., E-mail: pavelden@uvic.ca

2012-07-01

We show that the evolutionary track of a low-mass red giant should make an extended zigzag on the Hertzsprung-Russel diagram just after the bump luminosity if fast internal rotation and enhanced extra mixing in the radiative zone bring the temperature gradient close to the adiabatic one. This can explain both the location and peculiar surface chemical composition of Li-rich K giants studied by Kumar et al. We also discuss a striking resemblance between the photometric and composition peculiarities of these stars and giant components of RS CVn binaries. We demonstrate that the observationally constrained values of the temperature gradient inmore » the Li-rich K giants agree with the required rate of extra mixing only if the turbulence that is believed to be responsible for this extra mixing is highly anisotropic, with its associated transport coefficients in the horizontal direction strongly dominating over those in the vertical direction.« less

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.

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

Geller, Aaron M.; Leiner, Emily M.; Mathieu, Robert D.

Sub-subgiants are stars that are observed to be redder than normal main-sequence stars and fainter than normal subgiant (and giant) stars in an optical color–magnitude diagram (CMD). The red straggler stars, which lie redward of the red giant branch, may be related and are often grouped together with the sub-subgiants in the literature. These stars defy our standard theory of single-star evolution and are important tests for binary evolution and stellar collision models. In total, we identify 65 sub-subgiants (SSG) and red stragglers (RS) in 16 open and globular star clusters from the literature; 50 of these, including 43 sub-subgiants,more » pass our strict membership selection criteria (though the remaining sources may also be cluster members). In addition to their unique location on the CMD, we find that at least 58% (25/43) of sub-subgiants in this sample are X-ray sources with typical 0.5–2.5 keV luminosities of order 10{sup 30}–10{sup 31} erg s{sup −1}. Their X-ray luminosities and optical–to–X-ray flux ratios are similar to those of RS CVn active binaries. At least 65% (28/43) of the sub-subgiants in our sample are variables, 21 of which are known to be radial-velocity binaries. Typical variability periods are ≲15 days. At least 33% (14/43) of the sub-subgiants are H α emitters. These observational demographics provide strong evidence that binarity is important for sub-subgiant formation. Finally, we find that the number of sub-subgiants per unit mass increases toward lower-mass clusters, such that the open clusters in our sample have the highest specific frequencies of sub-subgiants.« less

The ultraviolet flux distribution of Alpha-2 Canum Venaticorum

NASA Technical Reports Server (NTRS)

Leckrone, D. S.; Snijders, M. A. J.

1979-01-01

Intermediate- and narrow-band UV spectrophotometry from Copernicus, OAO 2, the S2-68 experiment on TD 1, and a sounding-rocket experiment are combined with ground-based observations to define the absolute flux distribution of the bright magnetic Ap star Alpha-2 CVn over the wavelength range from 1030 to 7580 A. Two flux distributions are presented which coincide more or less with the rare-earth maximum and minimum in the star's cycle. The results are compared with those for two normal stars, the UV variability of Alpha-2 CVn is characterized as a function of wavelength, and non-LTE effects on the UV continua of C I and Si I are analyzed. Some physical properties of Alpha-2 CVn are estimated, and the evolutionary age of the star is estimated to be between 220 million and 300 million years. It is concluded that Alpha-2 CVn is old enough to have been magnetically braked to its current rotational velocity by either the centrifugal-wind or the accretion mechanism and to have developed its chemical peculiarities by either mechanism.

Two More Candidate AM Canum Venaticorum (am CVn) Binaries from the Sloan Digital Sky Survey

NASA Astrophysics Data System (ADS)

Anderson, Scott F.; Becker, Andrew C.; Haggard, Daryl; Prieto, Jose Luis; Knapp, Gillian R.; Sako, Masao; Halford, Kelly E.; Jha, Saurabh; Martin, Blake; Holtzman, Jon; Frieman, Joshua A.; Garnavich, Peter M.; Hayward, Suzanne; Ivezić, Željko; Mukadam, Anjum S.; Sesar, Branimir; Szkody, Paula; Malanushenko, Viktor; Richmond, Michael W.; Schneider, Donald P.; York, Donald G.

2008-06-01

AM CVn systems are a select group of ultracompact binaries with the shortest orbital periods of any known binary subclass; mass transfer is likely from a low-mass (partially-)degenerate secondary onto a white dwarf primary, driven by gravitational radiation. In the past few years, the Sloan Digital Sky Survey (SDSS) has provided five new AM CVns. Here we report on two further candidates selected from more recent SDSS data. SDSS J1208+3550 is similar to the earlier SDSS discoveries, recognized as an AM CVn via its distinctive spectrum which is dominated by helium emission. From the expanded SDSS Data Release 6 (DR6) spectroscopic area, we provide an updated surface density estimate for such AM CVns of order 10-3.1-10-2.5 deg-2 for 15 < g < 20.5. In addition, we present another new candidate AM CVn, SDSS J2047+0008, which was discovered in the course of follow-up of SDSS-II supernova candidates. It shows nova-like outbursts in multi-epoch imaging data; in contrast to the other SDSS AM CVn discoveries, its (outburst) spectrum is dominated by helium absorption lines, reminiscent of KL Dra, and 2003aw. The variability selection of SDSS J2047+0008 from the 300 deg2 of SDSS Stripe 82 presages further AM CVn discoveries in future deep, multicolor, and time-domain surveys such as the Large Synoptic Survey Telescope (LSST). The new additions bring the total SDSS yield to seven AM CVns thus far, a substantial contribution to this rare subclass, versus the dozen previously known. Includes optical observations obtained with the Sloan Digital Sky Survey I and II and the Apache Point Observatory (APO) 3.5 m telescope which is owned and operated by the Astrophysical Research Consortium (ARC), and the WIYN Observatory which is a joint facility of the University of Wisconsin, Indiana University, Yale University, and NOAO.

Excess Hα emission in chromospherically active binaries.

NASA Astrophysics Data System (ADS)

Montes, D.; Fernandez-Figueroa, M. J.; de Castro, E.; Cornide, M.

1995-02-01

We study the behaviour of the excess Hα emission in a sample of 51 chromospherically active binary systems (RS CVn and BY Dra classes), of different activity levels. This sample include the 27 stars analysed by Fernandez-Figueroa et al. (1994) and the new observations of 24 systems described by Montes et al. (1994b). By using the spectral subtraction technique (subtraction of a synthesized stellar spectrum constructed from reference stars of similar spectral type and luminosity class) we obtain the active-chromosphere contribution to the Hα line in these 51 systems. We have determined the excess Hα emission equivalent widths and converted it to surface fluxes. The Hα emissions arising from each component star were obtained when it was possible to deblend both contributions. The comparison of the excess Hα emission, obtained with the spectral subtraction technique, with other Hα activity indices allows us to conclude that this is the preferable activity indicator for binaries. The behaviour of the excess Hα emission as a function of the rotation has been analyzed. A slight decline toward longer rotational periods, P_rot_, and larger Rossby numbers, R_0_, is present in agreement with previous results using others activity indicators. We have compared the derived excess Hα emission fluxes with those obtained in the Ca II K and Hɛ lines finding that a good correlation exits between these three chromospheric activity indicators. The Hα losses seem to be more important than Ca II K losses for cooler stars, in fact all the system with Hα emission above the continuum are cooler than 5000K. Correlations with other activity indicators, (C IV in the transition region, and X-rays in the corona) indicate that the exponents of the power-law relations increase with the formation temperature of the spectral features.

mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

PubMed

Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

2014-08-01

Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

New O-C Observations for 150 Algols: Insight to the Origins of Period Shifts

NASA Astrophysics Data System (ADS)

Hoffman, D. I.; Harrison, T. E.; McNamara, B. J.; Vestrand, W. T.

2005-12-01

Many eclipsing binaries of type Algol, RS CVn, and W UMa have observed orbital period shifts. Of these, many show both increasing and decreasing period shifts. Two leading explanations for these shifts are third body effects and magnetic activity changing the oblateness of the secondary, though neither one can explain all of the observed period oscillations. The first-generation Robotic Optical Transient Search Experiment (ROTSE-I) based in Los Alamos, NM, was primarily designed to look for the optical counterparts to gamma-ray bursts as well as searching for other optical transients not detected in gamma-rays. The telescope, consisting of four 200mm camera lenses, can image the entire northern sky twice in a night, which is a very useful tool in monitoring relatively bright eclipsing binaries for period shifts. The public data release from ROTSE-I, the Northern Sky Variability Survey (NSVS), spans one year of data stating in April, 1999. O-C data for 150 eclipsing binaries are presented using the NSVS data. We revisit work by Borkovits and Hegedüs on some third body candidates in several eclipsing binary systems using recent AAVSO and NSVS data. Some unusual light curves of eclipsing binaries produced from NSVS data is presented and discussed.

The behaviour of the excess CA II H and K and Hɛ emissions in chromospherically active binaries.

NASA Astrophysics Data System (ADS)

Montes, D.; Fernandez-Figueroa, M. J.; Cornide, M.; de Castro, E.

1996-08-01

In this work we analyze the behaviour of the excess Ca II H and K and Hɛ emissions in a sample of 73 chromospherically active binary systems (RS CVn and BY Dra classes), of different activity levels and luminosity classes. This sample includes the 53 stars analyzed by Fernandez-Figueroa et al. (1994) and the observations of 28 systems described by Montes et al. (1995c). By using the spectral subtraction technique (subtraction of a synthesized stellar spectrum constructed from reference stars of spectral type and luminosity class similar to those of the binary star components) we obtain the active-chromosphere contribution to the Ca II H and K lines in these 73 systems. We have determined the excess Ca II H and K emission equivalent widths and converted them into surface fluxes. The emissions arising from each component were obtained when it was possible to deblend both contributions. We have found that the components of active binaries are generally stronger emitters than single active stars for a given effective temperature and rotation rate. A slight decline of the excess Ca II H and K emissions towards longer rotation periods, P_rot_, and larger Rossby numbers, R_0_, is found. When we use R_0_ instead of P_rot_ the scatter is reduced and a saturation at R_0_=~0.3 is observed. A good correlation between the excess Ca II K and Hɛ chromospheric emission fluxes has been found. The correlations obtained between the excess Ca II K emission and other activity indicators, (C IV in the transition region, and X-rays in the corona) indicate that the exponents of the power-law relations increase with the formation temperature of the spectral features.

Effects of microstructure on inverse fracture occurring during drop-weight tear testing of high-toughness X70 pipeline steels

NASA Astrophysics Data System (ADS)

Hwang, Byoungchul; Kim, Yang Gon; Lee, Sunghak; Kim, Nack J.; Yoo, Jang Yong

2005-02-01

The effects of microstructure on inverse fracture occurring in the hammer-impacted region were analyzed after conducting a drop-weight tear test (DWTT) on high-toughness pipeline steels. Three kinds of steels were fabricated by varying the alloying elements, and their microstructures were varied by the rolling conditions. The pressed-notch (PN) or chevron-notch (CN) DWTT and Charpy V-notch (CVN) impact tests were conducted on the rolled steel specimens, and the results were discussed in comparison with the data obtained from CVN tests of prestrained specimens. In the hammer-impacted region of the DWTT specimens, abnormal inverse fracture having a cleavage fracture mode appeared, and the inverse fracture area correlated well with the upper-shelf energy (USE) obtained from the CVN test and with the grain size. The steel specimens having a higher USE or having coarse polygonal ferrite tended to have a larger inverse fracture area than those having a lower USE or having fine acicular ferrite. This was because steels having a higher impact absorption energy required higher energy for fracture initiation and propagation during the DWTT. These results were confirmed by the CVN data of prestrained steel specimens.

A Survey of Ca II H and K Chromospheric Emission in Southern Solar-Type Stars

NASA Astrophysics Data System (ADS)

Henry, Todd J.; Soderblom, David R.; Donahue, Robert A.; Baliunas, Sallie L.

1996-01-01

More than 800 southern stars within 50 pc have been observed for chromospheric emission in the cores of the Ca II H and K lines. Most of the sample targets were chosen to be G dwarfs on the basis of colors and spectral types. The bimodal distribution in stellar activity first noted in a sample of northern stars by Vaughan and Preston in 1980 is confirmed, and the percentage of active stars, about 30%, is remarkably consistent between the northern and southern surveys. This is especially compelling given that we have used an entirely different instrumental setup and stellar sample than used in the previous study. Comparisons to the Sun, a relatively inactive star, show that most nearby solar-type stars have a similar activity level, and presumably a similar age. We identify two additional subsamples of stars -- a very active group, and a very inactive group. The very active group may be made up of young stars near the Sun, accounting for only a few percent of the sample, and appears to be less than ~0.1 Gyr old. Included in this high-activity tail of the distribution, however, is a subset of very close binaries of the RS CVn or W UMa types. The remaining members of this population may be undetected close binaries or very young single stars. The very inactive group of stars, contributting ~5%--10% to the total sample, may be those caught in a Maunder Minimum type phase. If the observations of the survey stars are considered to be a sequence of snapshots of the Sun during its life, we might expect that the Sun will spend about 10% of the remainder of its main sequence life in a Maunder Minimum phase.

Navy News Feature

Science.gov Websites

(Released) 180402-N-AM903-013 Naval Support Activity Bethesda (NSAB) conducts a proclamation signing for ) 180402-N-AM903-029 Command Master Chief of the aircraft carrier USS George H.W. Bush (CVN 77) Huben Specialist 3rd Class Mario Coto (Released) 180323-N-JC445-0134 Tamela Bryan, the deployed resiliency

Carbohydrate recognition by the antiviral lectin cyanovirin-N

PubMed Central

Fujimoto, Yukiji K.; Green, David F.

2012-01-01

Cyanovirin-N is a cyanobacterial lectin with potent antiviral activity, and has been the focus of extensive pre-clinical investigation as a potential prophylactic for the prevention of the sexual transmission of the human immunodeficiency virus (HIV). Here we present a detailed analysis of carbohydrate recognition by this important protein, using a combination of computational methods, including extensive molecular dynamics simulations and Molecular-Mechanics/ Poisson–Boltzmann/Surface-Area (MM/PBSA) energetic analysis. The simulation results strongly suggest that the observed tendency of wildtype CVN to form domain-swapped dimers is the result of a previously unidentified cis-peptide bond present in the monomeric state. The energetic analysis additionally indicates that the highest-affinity ligand for CVN characterized to date (α-Man-(1,2)-α-Man-(1,2)-α-Man) is recognized asymmetrically by the two binding sites. Finally, we are able to provide a detailed map of the role of all binding site functional groups (both backbone and side chain) to various aspects of molecular recognition: general affinity for cognate ligands, specificity for distinct oligosaccharide targets and the asymmetric recognition of α-Man-(1,2)-α-Man-(1,2)-α-Man. Taken as a whole, these results complement past experimental characterization (both structural and thermodynamic) to provide the most complete understanding of carbohydrate recognition by CVN to date. The results also provide strong support for the application of similar approaches to the understanding of other protein–carbohydrate complexes. PMID:23057413

Toughness characterization by small specimen test technique for HIPed joints of F82H steel aiming at first wall fabrication in fusion

NASA Astrophysics Data System (ADS)

Kishimoto, H.; Ono, T.; Sakasegawa, H.; Tanigawa, H.; Kohno, Y.; Kohyama, A.

2013-09-01

Reduced activation ferritic/martensitic steels (RAFMs), such as F82H steels, have been developed as candidates of structural materials for fusion. In the design of a fusion reactor, cooling channels are built in the first wall of the blanket. One large issue is to determine how to join rectangular tubes to thin panels to fabricate the first wall. Hot Isostatic Pressing (HIPing) is a solution to solve the issue. Because of the thin HIPed walls of the channels, the specimen size for inspection of HIPed interface is limited. In the present research, Small Specimen Test Techniques (SSTT) are screened for the destructive toughness investigation technique of HIPed F82H joints. 1/3 size Charpy V-notch impact (1/3 CVN) and small punch (SP) tests are employed for the present research. The toughness of the HIPed joints is strongly affected by various surface finishing of specimens treated previous to the HIPing. In the present research, several kinds of HIPed joints were surface finished by different methods and investigated by 1/3 CVN impact test. The HIPed F82H joints had different toughness ranging from 20% to 70% of the toughness of the F82H base metal. The SP test is also available for the investigation of toughness change by the HIPing. The sensitivity of 1/3 CVN impact test against toughness change was better than the SP test, it revealed that the SP test has some limitations.

Spectral Line Polarisation Atlases for 53 Cam (A4p) and alpha 2 CVn (A0p)

NASA Astrophysics Data System (ADS)

Wade, G. A.

2002-08-01

Wade, Donati & Landstreet (2000) presented a atlas of the R=35,000 Stokes IQUV spectrum of the cool magnetic Ap star beta CrB in the spectral range 450-660 nm. In this report we present analogous atlases for the well-studied magnetic Ap stars 53 Cam (HD 65339, A4p) and alpha 2 CVn (HD 112413, A0p).

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

DTIC Science & Technology

2009-09-01

345.37 1965.04 38.61 6266.69 Tanks Potable Water (100% Full) Reserve Feed Water (100% Full) JP-5 (95% Full) Bilge and Oily Water Storage Onboard...floating body..............................................................................10 Figure 6. Wooden block in water ...increased to 103,800 LT. CVN 76 has a higher displacement limit than the rest of the class due to some design changes below the water line (i.e

Flux variability in the K CA II and H-gamma lines of the AP stars 53 Cam, 41 Tau, Beta CrB, and Alpha(2) CVn

NASA Astrophysics Data System (ADS)

Kuvshinov, V. M.; Plachinda, S. I.

The rapid variability of the relative fluxes in the nuclei of the K Ca II and H-gamma lines of four typical Ap stars, 53 Cam, 41 Tau, Beta CrB, and Alpha(2) CVn, was studied during the period December 1979 - June 1980. Observations were carried out using the scanner-magnetograph of the 2.6-m reflector of the Crimean Astrophysical Observatory. In addition to relative flux variations with the phase of the axial rotation period of the stars, fluctuations of relative fluxes with characteristic times of several minutes to several hours were detected. The upper probability limit for such fluctuations, which are mostly irregular, is estimated at 35 percent for 53 Cam (K Ca II) and 56 percent for Alpha(2) CVn (H-gamma).

The magnetic fields of Ap stars from high resolution Stokes IQUV spectropolarimetry

NASA Astrophysics Data System (ADS)

Silvester, James

In this thesis we describe the acquisition of high resolution time resolved spectropolarimetric observations of 7 (bright and well understood) Ap stars in Stokes IQUV using the ESPaDOnS and Narval spectropolarimeters at the Canada-France-Hawaii Telescope and the 2m Telescope Bernard Lyot at Pic du Midi Observatory. We compare these observations with those obtained a decade earlier using the MuSiCoS spectropolarimeter to confirm consistency with the older data and provide evidence that both ESPaDOnS and Narval perform as expected in all Stokes parameters. We demonstrate that our refined longitudinal magnetic field and linear polarisation measurements for these 7 stars are of much greater quality than was previously obtained with MuSiCoS and that the global magnetic properties of these stars are stable over a long timescale. The ultimate aim of these new data is to provide a basis from which mapping of both the magnetic field and abundance structures can be performed on our target stars. We then describe magnetic field mapping of the Ap star alpha 2 CVn using these data. This mapping is achieved with the use of tomographic inversion of Doppler-broadened Stokes IQUV profiles of a large variety of spectral lines using the INVERS10 Magnetic Doppler imaging code. We show that not only are the new magnetic field maps of alpha 2 CVn consistent with a previous generation of maps of alpha 2 CVn, but that the same magnetic field topology can be derived from a variety of atomic line sets. This indicates that the magnetic field we derive for alpha2 CVn is a realistic representation of the star's true magnetic topology. Finally we investigate surface abundance structures for alpha 2 CVn for various chemical elements. We investigate the correlation between the location of these abundance features and the magnetic field of alpha 2 CVn. We will demonstrate that whilst the magnetic field plays a role in the formation of abundance structures, the current theoretical framework does not fully explain what we find from our maps. Ultimately this work motivates future mapping of Ap stars by confirming the reliability of both the instrument and associated data and the mapping technique itself.

Composition of the Active Fleet, U.S. Navy, 1961-1985.

DTIC Science & Technology

1980-12-01

Amberjack SS 324 Blenny SS 523 Grampus SS 331 Bugara SS 524 Pickerel SS 337 Carbonero SS 525 Grenadier SS 338 Carp SS 550 Barracuda SS 339 Catfish SS...LKA 57 Bordelon DD 881 Carbonero SS 337 Borie DD 704 Carl Vinson CVN 70 Boston CA 69 Caroline County LST 525 Boston SSN 703 Caron DD 970 Botetourt LPA

Convection Enhances Magnetic Turbulence in AM CVn Accretion Disks

NASA Astrophysics Data System (ADS)

Coleman, Matthew S. B.; Blaes, Omer; Hirose, Shigenobu; Hauschildt, Peter H.

2018-04-01

We present the results of local, vertically stratified, radiation magnetohydrodynamic shearing-box simulations of magnetorotational instability (MRI) turbulence for a (hydrogen poor) composition applicable to accretion disks in AM CVn type systems. Many of these accreting white dwarf systems are helium analogs of dwarf novae (DNe). We utilize frequency-integrated opacity and equation-of-state tables appropriate for this regime to accurately portray the relevant thermodynamics. We find bistability of thermal equilibria in the effective-temperature, surface-mass-density plane typically associated with disk instabilities. Along this equilibrium curve (i.e., the S-curve), we find that the stress to thermal pressure ratio α varied with peak values of ∼0.15 near the tip of the upper branch. Similar to DNe, we found enhancement of α near the tip of the upper branch caused by convection; this increase in α occurred despite our choice of zero net vertical magnetic flux. Two notable differences we find between DN and AM CVn accretion disk simulations are that AM CVn disks are capable of exhibiting persistent convection in outburst, and ideal MHD is valid throughout quiescence for AM CVns. In contrast, DNe simulations only show intermittent convection, and nonideal MHD effects are likely important in quiescence. By combining our previous work with these new results, we also find that convective enhancement of the MRI is anticorrelated with mean molecular weight.

Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV.

PubMed

O'Keefe, Barry R; Murad, André M; Vianna, Giovanni R; Ramessar, Koreen; Saucedo, Carrie J; Wilson, Jennifer; Buckheit, Karen W; da Cunha, Nicolau B; Araújo, Ana Claudia G; Lacorte, Cristiano C; Madeira, Luisa; McMahon, James B; Rech, Elibio L

2015-09-01

There is an urgent need to provide effective anti-HIV microbicides to resource-poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV-N was isolated with a yield of 350 μg/g of dry seed weight. The observed amino acid sequence of rCV-N matched the expected sequence of native CV-N, as did the mass of rCV-N (11 009 Da). Purified rCV-N from soya is active in anti-HIV assays with an EC50 of 0.82-2.7 nM (compared to 0.45-1.8 nM for E. coli-produced CV-N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV-N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti-HIV microbicide development. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

A New Photometric Investigation of the W UMa-Type Binary BI CVn

NASA Astrophysics Data System (ADS)

Qian, S.-B.; He, J.-J.; Liu, L.; Zhu, L.-Y.; Liao, W. P.

2008-12-01

New photometric observations and their investigation of the W UMa-type binary, BI CVn, are presented. The variations of the orbital period were analyzed based on 12 new determined times of light minimum together with the others compiled from the literature. It is discovered that the period of BI CVn shows a long-term period decrease at a rate of \\dot{P}=-1.51(± 0.12)× {10^{-7}} days year-1 while it undergoes a cyclic variation with a period of 27.0 years and an amplitude of 0fd0151. Photometric solutions determined with the Wilson-Devinney method suggest that BI CVn is a contact binary with a degree of contact of 18.0(±1.7)%. The asymmetry of the light curves was interpreted by the presence of dark spots on both components, and absolute parameters were determined by combining the photometric elements with the spectroscopic solutions given by Lu. The observed period decrease can be plausibly explained by a combination of the mass transfer from the primary to the secondary and angular momentum loss via magnetic braking. The cyclic period oscillation suggests that BI CVn is a triple system containing a tertiary component with a mass no less than 0.58 M sun in a 27.0 year orbit. As in the cases of the other contact binaries (e.g., AH Cnc, AP Leo, AD Cnc, and UX Eri), it is possible that this tertiary companion played an important role for the formation and evolution of the contact system by removing angular momentum from the central system via Kozai oscillation or a combination of Kozai cycle and tidal friction, which causes the eclipsing pair to have a short initial orbital period (e.g., P < 5d). In that case, can the initially detached system evolve into the present contact configuration via a combination of magnetic torques from stellar winds and a case A mass transfer?

Elastic - Plastic Fracture Mechanics. A Critical Review. Part 1

DTIC Science & Technology

1990-04-01

Rolfe and Novak (86) developed the following correlations for upper shelf toughness in steels: (KIC) 2 (CVN S) (3.301 where KiC is in ksi , CVN is in ft...lb, and ys isin ksi. The good correlation with Rolfe and Novak’s experimental data was attributed to upper shelf fracture not being as sensitive to...Pisarski (84) pointed out that much of Rolfe and Novak’s data did not meet the KIC size requirements and were therefore not valid. Rolfe and Barsom (87

Dynamic J sub I-R Curve Testing of HY-130 Steel.

DTIC Science & Technology

1981-10-01

Society for Testing and Materials 0C Degrees Celsius COD Crack-opening displacement CT Compact tension CVN Charpy V-notch dia Diameter in-lb/in 2 Inch...inches per second. A key curve for HY-130 plate was developed under dynamic loading conditions using subsized compact specimens and was applied to...face grooves were machined along the crack line to a total section reduction of 20% with a standard Charpy V-notch (CVN) cutter (450 included angle

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

DTIC Science & Technology

2010-05-26

online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600. 4 Department of Defense, Quadrennial Defense Review Report, February 2010...calculated by the “How Fair Is It?” online distance calculator available at http://www.indo.com/cgi-bin/dist. 10 Although the Navy states that the CVN based...itself. 14 This is the straight-line distance between the two locations, as calculated by the “How Fair Is It?” online distance calculator available

FIRST ZEEMAN DOPPLER IMAGING OF A COOL STAR USING ALL FOUR STOKES PARAMETERS

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

Rosén, L.; Kochukhov, O.; Wade, G. A.

Magnetic fields are ubiquitous in active cool stars, but they are in general complex and weak. Current Zeeman Doppler imaging (ZDI) studies of cool star magnetic fields chiefly employ circular polarization observations because linear polarization is difficult to detect and requires a more sophisticated radiative transfer modeling to interpret. But it has been shown in previous theoretical studies, and in the observational analyses of magnetic Ap stars, that including linear polarization in the magnetic inversion process makes it possible to correctly recover many otherwise lost or misinterpreted magnetic features. We have obtained phase-resolved observations in all four Stokes parameters ofmore » the RS CVn star II Peg at two separate epochs. Here we present temperature and magnetic field maps reconstructed for this star using all four Stokes parameters. This is the very first such ZDI study of a cool active star. Our magnetic inversions reveal a highly structured magnetic field topology for both epochs. The strength of some surface features is doubled or even quadrupled when linear polarization is taken into account. The total magnetic energy of the reconstructed field map also becomes about 2.1–3.5 times higher. The overall complexity is also increased as the field energy is shifted toward higher harmonic modes when four Stokes parameters are used. As a consequence, the potential field extrapolation of the four Stokes parameter ZDI results indicates that magnetic field becomes weaker at a distance of several stellar radii due to a decrease of the large-scale field component.« less

The Rise and Fall of μ Velorum: A Remarkable Flare on a Yellow Giant Star Observed with the Extreme Ultraviolet Explorer

NASA Astrophysics Data System (ADS)

Ayres, Thomas R.; Osten, Rachel A.; Brown, Alexander

1999-11-01

The close visual double μ Velorum (HD 93497; G6 III+dF) consists of a yellow giant and a fainter companion currently 2" apart. Recently μ Vel was the source of a large flare recorded by the Extreme Ultraviolet Explorer. The long 1.5 day decay phase was like the extremes seen on hyperactive RS CVn-type binaries. The primary, μ Vel A is a 3 Msolar star, in the ``rapid braking zone'' redward of G0 III. Yellow giants are not commonly reported as flare stars, perhaps because the first-crossers are relatively rare and not well represented in the observational samples. The secondary star is classified G2 V, but the 1700 Å energy distribution places it earlier on the main sequence, probably F4 or F5 V, in a class also not usually known for coronal variability. The long duration of the μ Vel event suggests that it occurred in a significantly elongated structure of moderate density, ne<~109 cm-3. If it was a magnetic plasmoid, like a coronal mass ejection on the Sun, then such events might play a role in shedding angular momentum from active evolved stars. The associated spin-down could control the activity survival time of red giants (in later stages of evolution than the first-crosser μ Vel) whose dynamos were rejunvenated by dredge-up of angular momentum from the interior, or more exotic sources, such as cannibalism of close-in substellar companions during the first or second ascent.

The double helium-white dwarf channel for the formation of AM CVn binaries

NASA Astrophysics Data System (ADS)

Zhang, Xian-Fei; Liu, Jin-Zhong; Jeffery, C. Simon; Hall, Philip D.; Bi, Shao-Lan

2018-01-01

Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by gravitational wave radiation. However, a significant fraction with low mass ratios will survive for a long time as a consequence of stable mass transfer. Such stable mass transfer between two helium white dwarfs (HeWDs) provides one channel for the production of AM CVn binary stars. In previous calculations of double HeWD progenitors, the accreting HeWD was treated as a point mass. We have computed the evolution of 16 double HeWD models in order to investigate the consequences of treating the evolution of both components in detail. We find that the boundary between binaries having stable and unstable mass transfer is slightly modified by this approach. By comparing with observed periods and mass ratios, we redetermine masses of eight known AM CVn stars by our double HeWDs channel, i.e. HM Cnc, AM CVn, V406 Hya, J0926, J1240, GP Com, Gaia14aae and V396 Hya.We propose that central spikes in the triple-peaked emission spectra of J1240, GP Com and V396 Hya and the surface abundance ratios of N/C/O in GP Com can be explained by the stable double HeWD channel. The mass estimates derived from our calculations are used to discuss the predicted gravitational wave signal in the context of the Laser Interferometer Space Antenna (LISA) project.

Genetic characterization of non-O157 verocytotoxigenic Escherichia coli isolated from raw beef products using multiple-locus variable-number tandem repeat analysis.

PubMed

Franci, Tomás; Sanso, A Mariel; Bustamante, Ana V; Lucchesi, Paula M A; Parma, Alberto E

2011-09-01

Verocytotoxigenic Escherichia coli (VTEC) can produce serious human illness linked to the consumption of contaminated food, mainly of bovine origin. There is growing concern about non-O157 VTEC serotypes, which in some countries cause severe infections in a proportion similar to O157:H7 strains. As several epidemiological studies indicated the important role of meat as the major vehicle in the transmission of this pathogen to human consumers, our aim was to investigate the genetic diversity among non-O157:H7 VTEC isolated from raw beef products. We performed a multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA), and to our knowledge, this is the first time that VTEC serotypes O8:H19, O112:H2, O113:NM, O171:NM, ONT:H7, ONT:H19, and ONT:H21 were typed by this method. MLVA typing grouped the total number of strains from this study (51) into 21 distinct genotypes, and 11 of them were unique. Several MLVA profiles were found in different serotypes, O178:H19 being the most variable. The isolates could be principally discriminated by alleles of three of seven loci studied (CVN001, CVN004, and CVN014), and on the other hand, CVN003 rendered null alleles in all the isolates. As some VNTR markers might be serotype specific, it is possible that the implementation of new VNTR loci will increase intraserotype discrimination.

Evolution of starspots in the long-period RS CVN binary V1817 Cygni = HR 7428

NASA Technical Reports Server (NTRS)

Hall, Douglas S.; Gessner, Susan E.; Lines, Helen C.; Lines, Richard D.

1990-01-01

Photometry between 1982 and 1989, published and unpublished, is analyzed. The ellipticity effect produces variability with a full amplitude of 0.033 m in V. A recent time of light minimum (JD 2445988.0 + or - 0.3 d) combined with an old spectroscopic time of conjunction from the 1920's yields a much improved orbital period (108.854 + or - 0.003). Removal of the ellipticity effect reveals starspot variability. Four different spots were observed at various times, two of them present simultaneously in the light curve during 1985. Mean spot lifetimes were around 2 years and the largest amplitude attributed to starspots was 0.04 m in V during 1986. Derived rotation periods for two spots were 5.3 + or - 1.2 percent slower than synchronous and 3.0 + or - 0.4 percent faster. The differential rotation coefficient for the K2 giant is k = 0.25 + or - 0.04, compared to k = 0.186 for the sun. V1817 Cygni has the longest orbital period of any binary known to execute synchronous rotation.

Stellar X-Ray Polarimetry

NASA Technical Reports Server (NTRS)

Swank, J.

2011-01-01

Most of the stellar end-state black holes, pulsars, and white dwarfs that are X-ray sources should have polarized X-ray fluxes. The degree will depend on the relative contributions of the unresolved structures. Fluxes from accretion disks and accretion disk corona may be polarized by scattering. Beams and jets may have contributions of polarized emission in strong magnetic fields. The Gravity and Extreme Magnetism Small Explorer (GEMS) will study the effects on polarization of strong gravity of black holes and strong magnetism of neutron stars. Some part of the flux from compact stars accreting from companion stars has been reflected from the companion, its wind, or accretion streams. Polarization of this component is a potential tool for studying the structure of the gas in these binary systems. Polarization due to scattering can also be present in X-ray emission from white dwarf binaries and binary normal stars such as RS CVn stars and colliding wind sources like Eta Car. Normal late type stars may have polarized flux from coronal flares. But X-ray polarization sensitivity is not at the level needed for single early type stars.

Variable Stars Observed in the Galactic Disk by AST3-1 from Dome A, Antarctica

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

Wang, Lingzhi; Ma, Bin; Hu, Yi

AST3-1 is the second-generation wide-field optical photometric telescope dedicated to time-domain astronomy at Dome A, Antarctica. Here, we present the results of an i -band images survey from AST3-1 toward one Galactic disk field. Based on time-series photometry of 92,583 stars, 560 variable stars were detected with i magnitude ≤16.5 mag during eight days of observations; 339 of these are previously unknown variables. We tentatively classify the 560 variables as 285 eclipsing binaries (EW, EB, and EA), 27 pulsating variable stars ( δ Scuti, γ Doradus, δ Cephei variable, and RR Lyrae stars), and 248 other types of variables (unclassifiedmore » periodic, multiperiodic, and aperiodic variable stars). Of the eclipsing binaries, 34 show O’Connell effects. One of the aperiodic variables shows a plateau light curve and another variable shows a secondary maximum after peak brightness. We also detected a complex binary system with an RS CVn-like light-curve morphology; this object is being followed-up spectroscopically using the Gemini South telescope.« less

Models for 60 double-lined binaries containing giants

NASA Astrophysics Data System (ADS)

Eggleton, Peter P.; Yakut, Kadri

2017-07-01

The observed masses, radii and temperatures of 60 medium- to long-period binaries, most of which contain a cool, evolved star and a hotter less evolved one, are compared with theoretical models which include (a) core convective overshooting, (b) mass-loss, possibly driven by dynamo action as in RS CVn binaries, and (c) tidal friction, including its effect on orbital period through magnetic braking. A reasonable fit is found in about 42 cases, but in 11 other cases the primaries appear to have lost either more mass or less mass than the models predict, and in 4 others the orbit is predicted to be either more or less circular than observed. Of the remaining three systems, two (γ Per and HR 8242) have a markedly 'overevolved' secondary, our explanation being that the primary component is the merged remnant of a former short-period sub-binary in a former triple system. The last system (V695 Cyg) defies any agreement at present. Mention is also made of three other systems (V643 Ori, OW Gem and V453 Cep), which are relevant to our discussion.

Initial results from the extreme ultraviolet explorer

NASA Technical Reports Server (NTRS)

Bowyer, S.; Malina, R. F.

1993-01-01

Data obtained during the first five months of calibration and science operation of the Extreme Ultraviolet Explorer (EUVE) are presented. Spectra of an extragalactic object were obtained; the object is detectable to wavelenghts longer than 100 A, demonstrating that extragalactic EUV astronomy is possible. Spectra of a hot white dwarf, and a late-type star in quiescence and flaring are shown as examples of the type of spectrographic data obtainable with EUVE. Other objects for which broad band photometric mode data have been obtained and analyzed include an RS CVn star and several late-type stars. The backgrounds in the EUVE detectors are quite low and the character of the diffuse astronomical EUV background has been investigated using these very low rates. Evidence is presented showing that, contrary to previously published reports, EUVE is about three times more sensitive than the English Wide Field Camera in the short wavelength bandpass covered by both instruments. Only limited information has been extracted from the longer bandpasses coered only by EUVE. Nonetheless, the brightest EUV source in the sky, a B star, has been discovered and is detected only in these longer bandpasses.

Color Vision and Performance on Color-Coded Cockpit Displays.

PubMed

Gaska, James P; Wright, Steven T; Winterbottom, Marc D; Hadley, Steven C

Although there are numerous studies that demonstrate that color vision deficient (CVD) individuals perform less well than color vision normal (CVN) individuals in tasks that require discrimination or identification of colored stimuli, there remains a need to quantify the relationship between the type and severity of CVD and performance on operationally relevant tasks. Participants were classified as CVN (N = 45) or CVD (N = 49) using the Rabin cone contrast test, which is the standard color vision screening test used by the United States Air Force. In the color condition, test images that were representative of the size, shape, and color of symbols and lines used on fifth-generation fighter aircraft displays were used to measure operational performance. In the achromatic condition, all symbols and lines had the same chromaticity but differed in luminance. Subjects were asked to locate and discriminate between friend vs. foe symbols (red vs. green, or brighter vs. dimmer) while speed and accuracy were recorded. Increasing color deficiency was associated with decreasing speed and accuracy for the color condition (R 2 > 0.2), but not for the achromatic condition. Mean differences between CVN and CVD individuals showed the same pattern. Although lower CCT scores are clearly associated with lower performance in color related tasks, the magnitude of the performance loss was relatively small and there were multiple examples of high-performing CVD individuals who had higher operational scores than low-performing CVN individuals. Gaska JP, Wright ST, Winterbottom MD, Hadley SC. Color vision and performance on color-coded cockpit displays. Aerosp Med Hum Perform. 2016; 87(11):921-927.

Effective grain size and charpy impact properties of high-toughness X70 pipeline steels

NASA Astrophysics Data System (ADS)

Hwang, Byoungchul; Kim, Yang Gon; Lee, Sunghak; Kim, Young Min; Kim, Nack J.; Yoo, Jang Yong

2005-08-01

The correlation of microstructure and Charpy V-notch (CVN) impact properties of a high-toughness API X70 pipeline steel was investigated in this study. Six kinds of steel were fabricated by varying the hot-rolling conditions, and their microstructures, effective grain sizes, and CVN impact properties were analyzed. The CVN impact test results indicated that the steels rolled in the single-phase region had higher upper-shelf energies (USEs) and lower energy-transition temperatures (ETTs) than the steels rolled in the two-phase region because their microstructures were composed of acicular ferrite (AF) and fine polygonal ferrite (PF). The decreased ETT in the steels rolled in the single-phase region could be explained by the decrease in the overall effective grain size due to the presence of AF having a smaller effective grain size. On the other hand, the absorbed energy of the steels rolled in the two-phase region was considerably lower because a large amount of dislocations were generated inside PFs during rolling. It was further decreased when coarse martensite or cementite was formed during the cooling process.

Transformation of Althaea officinalis L. by Agrobacterium rhizogenes for the production of transgenic roots expressing the anti-HIV microbicide cyanovirin-N.

PubMed

Drake, Pascal M W; de Moraes Madeira, Luisa; Szeto, Tim H; Ma, Julian K-C

2013-12-01

The marshmallow plant (Althaea officinalis L.) has been used for centuries in medicine and other applications. Valuable secondary metabolites have previously been identified in Agrobacterium rhizogenes-generated transgenic 'hairy' roots in this species. In the present study, transgenic roots were produced in A. officinalis using A. rhizogenes. In addition to wild-type lines, roots expressing the anti-human immunodeficiency virus microbicide candidate, cyanovirin-N (CV-N), were generated. Wild-type and CV-N root lines were transferred to liquid culture and increased in mass by 49 and 19 % respectively over a 7 day culture period. In the latter, the concentration of CV-N present in the root tissue was 2.4 μg/g fresh weight, with an average secretion rate into the growth medium of 0.02 μg/ml/24 h. A. officinalis transgenic roots may therefore in the future be used not only as a source of therapeutic secondary metabolites, but also as an expression system for the production of recombinant pharmaceuticals.

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.

V405 ANDROMEDA REVISITED

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

Ribeiro, T.; Baptista, R.; Kafka, S.

We present a multi-epoch time-resolved high-resolution optical spectroscopy study of the short-period (P{sub orb} = 11.2 hr) eclipsing M0V+M5V RS CVn binary V405 Andromeda. By means of indirect imaging techniques, namely Doppler imaging, we study the surface activity features of the M0V component of the system. A modified version of a Doppler imaging code, which takes into account the tidal distortion of the surface of the star, is applied to the multi-epoch data set in order to provide indirect images of the stellar surface. The multi-epoch surface brightness distributions show a low intensity 'belt' of spots at latitudes {+-}40{sup 0}more » and a noticeable absence of high latitude features or polar spots on the primary star of V405 Andromeda. They also reveal slow evolution of the spot distribution over {approx}4 yr. An entropy landscape procedure is used in order to find the set of binary parameters that lead to the smoothest surface brightness distributions. As a result, we find M{sub 1} = 0.51 {+-} 0.03 M{sub sun}, M{sub 2} = 0.21 {+-} 0.01 M{sub sun}, R{sub 1} = 0.71 {+-} 0.01 R{sub sun}, and an inclination i = 65{sup 0} {+-} 1{sup 0}. The resulting systemic velocity is distinct for different epochs, raising the possibility of the existence of a third body in the system.« less

The Spot Variability and Related Brightness variations of the Solar Type PreContact W UMa Binary System V1001 Cas

NASA Astrophysics Data System (ADS)

Samec, Ronald George; Koenke, Sam S.; Faulkner, Danny R.

2015-08-01

A new classification of eclipsing binary has emerged, Pre Contact WUMa Binaries (PCWB’s, Samec et al. 2012). These solar-type systems are usually detached or semidetached with one or both components under filling their critical Roche lobes. They usually have EA or EB-type light curves (unequal eclipse depths, indicating components with substantially different temperatures). The accepted scenario for these W UMa binaries is that they are undergoing steady but slow angular momentum losses due to magnetic braking as stellar winds blow radially away on stiff bipolar field lines. These binaries are believed to come into stable contact and eventually coalesce into blue straggler type, single, fast rotating A-type stars (Guinan and Bradstreet,1988). High precision 2012 and 2009 light curves are compared for the very short period (~0.43d) Precontact W UMa Binary (PCWB), V1001 Cassiopeia. This is the shortest period PCWB found so far. Its short period, similar to the majority of W UMa’s, in contrast to its distinct Algol-type light curve, make it a very rare and interesting system. Our solutions of light curves separated by some three years give approximately the same physical parameters. However the spots radically change, in temperature, area and position causing a distinctive variation in the shape of the light curves. We conclude that spots are very active on this solar type dwarf system and that it may mimic its larger cousins, the RS CVn binaries.

Determining the nature of faint X-ray sources from the ASCA Galactic center survey

NASA Astrophysics Data System (ADS)

Lutovinov, A. A.; Revnivtsev, M. G.; Karasev, D. I.; Shimansky, V. V.; Burenin, R. A.; Bikmaev, I. F.; Vorob'ev, V. S.; Tsygankov, S. S.; Pavlinsky, M. N.

2015-05-01

We present the results of the the identification of six objects from the ASCA Galactic center and Galactic plane surveys: AX J173548-3207, AX J173628-3141, AX J1739.5-2910, AX J1740.4-2856, AX J1740.5-2937, and AX J1743.9-2846. Chandra, XMM-Newton, and XRT/Swift X-ray data have been used to improve the positions of the optical counterparts to these sources. Thereafter, we have carried out a series of spectroscopic observations of the established optical counterparts at the RTT-150 telescope. Analysis of X-ray and optical spectra as well as photometric measurements in a wide wavelength range based on optical and infrared catalogs has allowed the nature of the program sources to be determined. Two X-ray objects have been detected in the error circle of AX J173628-3141: one is a coronally active G star and the other may be a symbiotic star, a red giant with an accreting white dwarf. Three sources (AX J1739.5-2910, AX J1740.5-2937, AX J1743.9-2846) have turned out to be active G-K stars, presumably RS CVn objects, one (AX J1740.4-2856) is an M dwarf, and another one (AX J173548-3207) most likely a low-mass X-ray binary in its low state. The distances and corresponding luminosities of the sources in the soft X-ray band (0.5-10 keV) have been estimated; analysis of deep INTEGRAL Galactic center observations has not revealed a statistically significant flux at energies >20 keV from any of them.

Heavy-section steel irradiation program. Progress report, April 1996--September 1996

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

Corwin, W.R.

1997-09-01

The Heavy-Section Steel Irradiation Program was established to quantitatively assess the effects of neutron irradiation on the material behavior of typical reactor pressure vessel (RPV) steels. During this period, fracture mechanics testing of specimens of the irradiated low upper shelf (LUS) weld were completed and analyses performed. Heat treatment of five RPV plate materials was initiated to examine phosphorus segregation effects on the fracture toughness of the heat affected zone of welds. Initial results show that all five materials exhibited very large prior austenite grain sizes as a consequence of the initial heat treatment. Irradiated and annealed specimens of LUSmore » weld material were tested and analyzed. Four sets of Charpy V-notch (CVN) specimens were aged at various temperatures and tested to examine the reason for overrecovery of upper shelf energy that has been observed. Molecular dynamics cascade simulations were extended to 40 keV and have provided information representative of most of the fast neutron spectrum. Investigations of the correlation between microstructural changes and hardness changes in irradiated model alloys was also completed. Preliminary planning for test specimen machining for the Japan Power Development Reactor was completed. A database of Charpy impact and fracture toughness data for RPV materials that have been tested in the unirradiated and irradiated conditions is being assembled and analyzed. Weld metal appears to have similar CVN and fracture toughness transition temperature shifts, whereas the fracture toughness shifts are greater than CVN shifts for base metals. Draft subcontractor reports on precracked cylindrical tensile specimens were completed, reviewed, and are being revised. Testing on precracked CVN specimens, both quasi-static and dynamic, was evaluated. Additionally, testing of compact specimens was initiated as an experimental comparison of constraint limitations. 16 figs., 2 tabs.« less

Director, Operational Test and Evaluation FY 2006 Annual Report

DTIC Science & Technology

2006-12-01

Comstock ( LSD 45); and the USS McClusky (FFG 41). Activity • In Aprl 2006, the Jont Interoperablty Test Command conducted a Generation One, IOC 2...Monthan AFB, Arizona; the 609th Air Mobility Operations Squadron at Shaw AFB, South Carolina; the 83rd Communications Squadron at Langley AFB...as the combat system in LSD 41/49-class ships. • SSDS Mark 2 has four variants: - The Mod 1 is in development for CVN 68 class aircraft carrers

A Comparison of Mechanical Properties and Hydrogen Embrittlement Resistance of Austempered vs Quenched and Tempered 4340 Steel

NASA Astrophysics Data System (ADS)

Tartaglia, John M.; Lazzari, Kristen A.; Hui, Grace P.; Hayrynen, Kathy L.

2008-03-01

This study was conducted to compare the hydrogen embrittlement (HE) resistance of austempered 4340 steel with quenched and tempered (Q&T) 4340 steel with an identical yield strength (YS) of 1340 MPa (194 ksi). A baseline comparison showed that the austempered steel with a lower bainite microstructure exhibited higher hardness, tensile strengths, Charpy V-notch (CVN) impact toughness, and ductility at both low 233 K (-40 F) and ambient temperatures, as compared to the Q&T steel with a martensite microstructure. After machining and just prior to testing, subsized CVN specimens and notched bend specimens were immersed in hydrochloric acid-water baths. The HE resistance was higher for the austempered steel than the Q&T steel. No differences in room-temperature CVN energy resulted from hydrogen charging of the austempered and Q&T steels vs their unexposed counterparts. However, in the notched bend specimens, the hydrogen charging caused significant peak load decreases (40 pct) for the Q&T steel, while the austempered steel exhibited only small (6 pct) decreases in peak load. Intergranular (IG) fracture occurred solely in the charged Q&T bend samples, which is further evidence of their embrittlement.

A VLA radio-continuum survey of a sample of confirmed and marginal barium stars

NASA Technical Reports Server (NTRS)

Drake, Stephen A.; Simon, Theodore; Linsky, Jeffrey L.

1987-01-01

Results are reported from a 6-cm VLA survey of five confirmed Ba II stars and eight mild Ba II stars, undertaken to search for evidence of gyrosynchrotron emission or thermal emission from the primary star's wind that is enhanced or photoionized by a white dwarf companion. Of these 13 stars, only Beta UMi was detected as a possible radio source at a flux level of 0.11 mJy (3sigma). The 6-cm radio luminosities (L6) of the other stars are as small as log L6 less than or equal to 14.0 and are an order of magnitude or more lower than the average levels found in RS CVn systems, but are consistent with the L6 upper limits previously found for stars of spectral type similar to the Ba II stars and normal elemental abundances. The upper limit to the radio luminosity for the possible mild Ba II star 56 Peg, when combined with its previously known X-ray luminosity, may provide useful constraints on the various models that have been proposed for this interesting object, once its orbital period is known.

Spectroscopic Evidence for Nonuniform Starspot Properties on II Pegasi

NASA Technical Reports Server (NTRS)

ONeal, Douglas; Saar, Steven H.; Neff, James E.

1998-01-01

We present spectroscopic evidence for Multiple Spot temperatures on the RS CVn star II Pegasi (HD 224085). We model the strengths of the 7055 and 8860 A TiO absorption bands in the spectrum of II Peg using weighted sums of inactive comparison spectra: a K star to represent the nonspotted photosphere and an M star to represent the spots. The best fit yields independent measurements of the starspot filling factor (f(sub s) and mean spot temperature (T(sub s)) averaged over the visible hemisphere of the star. During three-fourths of a rotation of II Peg in late 1996, we measure a constant f(sub s) approximately equals 55% +/- 5%. However, (T(sub s) varies from 3350 +/- 60 to 3550 +/- 70 K. We compute (T(sub s) for two simple models: (1) a star with two distinct spot temperatures, and (2) a star with different umbral/penumbral area ratios. The changing (T(sub s) correlates with emission strengths of H(alpha) and the Ca II infrared triplet in the sense that cooler (T(sub s) accompanies weaker emission. We explore possible implications of these results for the physical properties of the spots on II Peg and for stellar surface structure in general.

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

Kim, Chun-Hwey; Song, Mi-Hwa; Yoon, Jo-Na

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. Themore » 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.« less

The AAVSO Photoelectric Photometry Program in its Scientific and Socio-Historic Context

NASA Astrophysics Data System (ADS)

Percy, John R.

2011-05-01

Photoelectric photometry began in the 1900s through the work of Guthnick, Stebbins, and others who constructed and used photometers based on the recently-discovered photoelectric effect. The mid 20th century saw a confluence of several areas of amateur interest: astronomy, telescope making, radio and electronics, and general interest in space. This is the time when AAVSO photoelectric photometry (PEP) began, with observers using mostly hand-built photometers on hand-built telescopes. The 1980s brought a revolution: affordable off-the-shelf solid-state photometers, and infrastructure such as the International Amateur-Professional Photoelectric Photometry (IAPPP) conferences, books, and journal. The AAVSO developed a formal PEP program in the early 1980s. Its emphasis was on long-term monitoring of pulsating red giants. It was competing, not always successfully, with programs such as active sun-like binaries (RS CVn stars) which offered "instant gratification" in the form of publicity and quick publications. Nevertheless, the AAVSO PEP program has, through careful organization, motivation, and feedback to observers, produced extensive scientific results. In this presentation, I shall describe, as examples, my own work, its scientific significance, its educational benefit to dozens of my students, and its satisfaction to the observers. To some extent, the AAVSO PEP program has been superceded by its CCD program, but there is still a useful place for ongoing PEP observations of thousands of variable stars. Reference: http://www.aavso.org/sites/default/files/newsletter/PEP/lastpepnl.pdf Acknowledgements: I thank NSERC Canada for research support, my students, and AAVSO staff and observers, especially Howard Landis.

A 15.7-Minute AM CVn Binary Discovered in K2

NASA Astrophysics Data System (ADS)

Green, M. J.; Hermes, J. J.; Marsh, T. R.; Steeghs, D. T. H.; Bell, Keaton J.; Littlefair, S. P.; Parsons, S. G.; Dennihy, E.; Fuchs, J. T.; Reding, J. S.; Kaiser, B. C.; Ashley, R. P.; Breedt, E.; Dhillon, V. S.; Gentile Fusillo, N. P.; Kerry, P.; Sahman, D. I.

2018-04-01

We present the discovery of SDSS J135154.46-064309.0, a short-period variable observed using 30-minute cadence photometry in K2 Campaign 6. Follow-up spectroscopy and high-speed photometry support a classification as a new member of the rare class of ultracompact accreting binaries known as AM CVn stars. The spectroscopic orbital period of 15.65 ± 0.12 minutes makes this system the fourth-shortest period AM CVn known, and the second system of this type to be discovered by the Kepler spacecraft. The K2 data show photometric periods at 15.7306 ± 0.0003 minutes, 16.1121 ± 0.0004 minutes and 664.82 ± 0.06 minutes, which we identify as the orbital period, superhump period, and disc precession period, respectively. From the superhump and orbital periods we estimate the binary mass ratio q = M2/M1 = 0.111 ± 0.005, though this method of mass ratio determination may not be well calibrated for helium-dominated binaries. This system is likely to be a bright foreground source of gravitational waves in the frequency range detectable by LISA, and may be of use as a calibration source if future studies are able to constrain the masses of its stellar components.

A 15.7-minAM CVn binary discovered in K2

NASA Astrophysics Data System (ADS)

Green, M. J.; Hermes, J. J.; Marsh, T. R.; Steeghs, D. T. H.; Bell, Keaton J.; Littlefair, S. P.; Parsons, S. G.; Dennihy, E.; Fuchs, J. T.; Reding, J. S.; Kaiser, B. C.; Ashley, R. P.; Breedt, E.; Dhillon, V. S.; Gentile Fusillo, N. P.; Kerry, P.; Sahman, D. I.

2018-07-01

We present the discovery of SDSS J135154.46-064309.0, a short-period variable observed using 30-mincadence photometry in K2 Campaign 6. Follow-up spectroscopy and high-speed photometry support a classification as a new member of the rare class of ultracompact accreting binaries known as AM CVn stars. The spectroscopic orbital period of 15.65 ± 0.12 min makes this system the fourth-shortest-period AM CVn known, and the second system of this type to be discovered by the Kepler spacecraft. The K2 data show photometric periods at 15.7306 ± 0.0003 min, 16.1121 ± 0.0004 min, and 664.82 ± 0.06 min, which we identify as the orbital period, superhump period, and disc precession period, respectively. From the superhump and orbital periods we estimate the binary mass ratio q = M2/M1= 0.111 ± 0.005, though this method of mass ratio determination may not be well calibrated for helium-dominated binaries. This system is likely to be a bright foreground source of gravitational waves in the frequency range detectable by Laser Interferometer Space Antenna, and may be of use as a calibration source if future studies are able to constrain the masses of its stellar components.

Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients.

PubMed

Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan; Mora-Jensen, Helena; Krogh, Anders; Kohlmann, Alexander; Thiede, Christian; Borregaard, Niels; Bullinger, Lars; Winther, Ole; Theilgaard-Mönch, Kim; Porse, Bo T

2014-02-06

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.

The unusual helium variable AM Canum Venaticorum

NASA Technical Reports Server (NTRS)

Provencal, J. L.; Winget, D. E.; Nather, R. E.; Robinson, E. L.; Solheim, J.-E.; Clemens, J. C.; Bradley, J. L.; Kleinman, S. J.; Kanaan, A.; Claver, C. F.

1995-01-01

The unusual variable star AM CVn has puzzled astronomers for over 40 years. This object, both a photometric and spectroscopic variable, is believed to contain a pair of hydrogen-deficient white dwarfs of extreme mass ratio, transferring material via an accretion disk. We examine the photometric properties of AM CVn, analyzing 289 hours of high-speed photometric data spanning 1976 to 1992. The power spectrum displays significant peaks at 988.7, 1248.8, 1902.5, 2853.8, 3805.2, 4756.5, and 5707.8 microHz (1011.4, 800.8, 525.6, 350.4, 262.8, 210.2, and 175.2 s). We find no detectable power at 951.3 microHz (1051 s), the previously reported main frequency. The 1902.5, 2853.9, and 3805.2 microHz peaks are multiplets, with frequency splitting in each case of 20.77 +/- 0.05 microHz. The 1902.5 microHz seasonal pulse shapes are identical, within measurement noise, and maintain the same amplitude and phase as a function of color. We have determined the dominant frequency to be 1902.50902 +/- 0.00001 microHz with dot P = +1.71 (+/- 0.04) x 10(exp -11) s/s. We discuss the implications of these findings on a model for AM CVn.

Influence of cytochrome P450 oxidoreductase genetic polymorphisms on CYP1A2 activity and inducibility by smoking.

PubMed

Dobrinas, Maria; Cornuz, Jacques; Pedrido, Leticia; Eap, Chin B

2012-02-01

Cytochrome P4501A2 (CYP1A2) presents a high interindividual variability in its activity and also in its inducibility by smoking. Cytochrome P450 oxidoreductase (POR) is an electron transfer protein that catalyzes the activity of several cytochromes P450. We aimed to study the influence of POR genetic polymorphisms on CYP1A2 activity while smoking and after smoking cessation, as well as on CYP1A2 inducibility. CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of these smokers who were abstinent during a 4-week period. Participants were genotyped for POR rs17148944G>A, rs10239977C>T, rs3815455C>T, rs2286823G>A, rs2302429G>A, and rs1057868C>T (POR*28) polymorphisms. While smoking, none of the tested POR polymorphisms showed a significant influence on CYP1A2 activity. After smoking cessation, significantly higher CYP1A2 activity was found in POR rs2302429A carriers (P=0.038) and in carriers of rs17148944G-rs10239977C-rs3815455T-rs2286823G-rs2302429A-rs1057868T haplotype (P=0.038), whereas carriers of POR rs2286823A (P=0.031) and of the rs17148944G-rs10239977C-rs3815455C-rs2286823A-rs2302429G-rs1057868C haplotype (P=0.031) had decreased CYP1A2 activity. In the complete regression model, only POR rs2302429G>A showed a significant effect (P=0.017). No influence of POR genotypes or haplotypes was observed on the inducibility of CYP1A2. POR genetic polymorphisms influence CYP1A2 basal but not induced activity and do not seem to influence CYP1A2 inducibility. Future work is warranted to identify other clinical and genetic factors that may explain the variability in CYP1A2 activity and inducibility by smoking.

HI emission from the red giant Y CVn with the VLA and FAST

NASA Astrophysics Data System (ADS)

Hoai, Do T.; Nhung, Pham T.; Matthews, Lynn D.; Gérard, Eric; Le Bertre, Thibaut

2017-07-01

Imaging studies with the Very Large Array (VLA) have revealed HI emission associated with the extended circumstellar shells of red giants. We analyze the spectral map obtained on Y CVn, a J-type carbon star on the Asymptotic Giant Branch. The HI line profiles can be interpreted with a model of a detached shell resulting from the interaction of a stellar outflow with the local interstellar medium. We reproduce the spectral map by introducing a distortion along a direction corresponding to the star’s motion in space. We then use this fitting to simulate observations expected from the Five-hundred-meter Aperture Spherical radio Telescope (FAST), and discuss its potential for improving our description of the outer regions of circumstellar shells.

[Construction and function identification of luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR].

PubMed

Yang, Shuo; Li, Jia-li; Bi, Hui-chang; Zhou, Shou-ning; Liu, Xiao-man; Zeng, Hang; Hu, Bing-fang; Huang, Min

2016-01-01

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.

Changing Aircraft Carrier Procurement Schedules: Effects that a Five-Year Procurement Cycle would have on Cost, Availability, and Shipyard Manpower and Workload

DTIC Science & Technology

2011-01-01

Staff, the Unified Combatant Commands, the Navy, the Marine Corps, the defense agencies, and the defense Intelligence Community under Contract W74V8H...Unified Combatant Commands, the Navy, the Marine Corps, the defense agencies, and the defense Intel- ligence Community . For more information on the...the Cuban missile crisis of October 1962. The newest active air- craft carrier, the Nimitz-class USS George H. W. Bush (CVN 77), was 1 CVN is an

VizieR Online Data Catalog: Equivalent width of 21 RR Lyrae stars (Pancino+, 2015)

NASA Astrophysics Data System (ADS)

Pancino, E.; Britavskiy, N.; Romano, D.; Cacciari, C.; Mucciarelli, A.; Clementini, G.

2015-02-01

Equivalent widths and atomic data of the absorption lines used in the abundance analysis, for each separate exposure at different phases. Observations of 15 RR Lyrae stars (DR And, X Ari, TW Boo, RZ Cam, RX Cet, U Com, RV CrB, SW CVn, UZ CVn, AE Dra, SZ Gem, VX Her, DH Hya, TU UMa, and RV UMa) and one BL Her star (UY Eri) were carried out with SARG@TNG, operated on the island of La Palma, Spain, during two separate runs in 2009 March and between September and November. Eight stars (SW Aqr, TW Cap, DH Hya, V Ind, SS Leo, V716 Oph, BK Tuc, and UV Vir) were observed with UVES@VLT, between 2009 April and August in service mode. (3 data files).

The RECONS Hunt for Intriguing Binaries in the Solar Neighborhood

NASA Astrophysics Data System (ADS)

Bean, J. L.; Henry, T. J.; Jao, W. C.; Subasavage, J. P.

2001-12-01

As part of an effort to characterize the Sun's neighbors, photometric research was carried out on two samples of low-mass stars known or suspected to lie within 25 parsecs of the Sun. Quality filtered optical photometric data (UBVRI) from published research were merged with recently released infrared data (JHK) from the Two Micron All Sky Survey (2MASS) to create comprehensive long baseline V-I or V-K colors for more than 1400 stars. These were then combined with parallaxes from the NStars Database to create color-absolute magnitude diagrams. The results of this research include increasing the breadth of the NStars Database by adding photometric data for over 1400 stars, and identifying intriguing multiple systems (close spectroscopic binaries, BY Dra types, RS CVn systems) as well as white dwarfs and evolved stars in the solar neighborhood. More than two dozen objects have been identified as probable new multiple systems from their positions above the main sequence. Additional investigations for these intriguing systems are planned, including observations made with the GSU CHARA Array to resolve very close binary systems. This research is a continuation of the work done by RECONS (Research Consortium on Nearby Stars) based at Georgia Sate U., Johns Hopkins U., and U. Virginia, and NASA's Nearby Stars Project (NStars).

Tidal Synchronization and Differential Rotation of Kepler Eclipsing Binaries

NASA Astrophysics Data System (ADS)

Lurie, John C.; Vyhmeister, Karl; Hawley, Suzanne L.; Adilia, Jamel; Chen, Andrea; Davenport, James R. A.; Jurić, Mario; Puig-Holzman, Michael; Weisenburger, Kolby L.

2017-12-01

Few observational constraints exist for the tidal synchronization rate of late-type stars, despite its fundamental role in binary evolution. We visually inspected the light curves of 2278 eclipsing binaries (EBs) from the Kepler Eclipsing Binary Catalog to identify those with starspot modulations, as well as other types of out-of-eclipse variability. We report rotation periods for 816 EBs with starspot modulations, and find that 79% of EBs with orbital periods of less than 10 days are synchronized. However, a population of short-period EBs exists, with rotation periods typically 13% slower than synchronous, which we attribute to the differential rotation of high-latitude starspots. At 10 days, there is a transition from predominantly circular, synchronized EBs to predominantly eccentric, pseudosynchronized EBs. This transition period is in good agreement with the predicted and observed circularization period for Milky Way field binaries. At orbital periods greater than about 30 days, the amount of tidal synchronization decreases. We also report 12 previously unidentified candidate δ Scuti and γ Doradus pulsators, as well as a candidate RS CVn system with an evolved primary that exhibits starspot occultations. For short-period contact binaries, we observe a period-color relation and compare it to previous studies. As a whole, these results represent the largest homogeneous study of tidal synchronization of late-type stars.

The most plausible explanation of the cyclic period changes in close binaries: the case of the RS CVn-type binary WW Dra

NASA Astrophysics Data System (ADS)

Liao, W.-P.; Qian, S.-B.

2010-07-01

Cyclic period changes are a fairly common phenomenon in close binary systems and are usually explained as being caused either by the magnetic activity of one or both components or by the light travel time effect (LTTE) of a third body. We searched the orbital period changes in 182 EA-type (including the 101 Algol systems used by Hall), 43 EB-type and 53 EW-type binaries with known mass ratio and spectral type of the secondary component. We reproduced and improved the diagram in Hall according to the new collected data. Our plots do not support the conclusion derived by Hall that cyclic period changes are restricted to binaries having a secondary component with spectral type later than F5. The presence of period changes among systems with a secondary component of early type indicates that magnetic activity is one, but not the only, cause of the period variation. It is discovered that cyclic period changes, probably resulting from the presence of a third body, are more frequent in EW-type binaries among close systems. Therefore, the most plausible explanation of the cyclic period changes is the LTTE through the presence of a third body. Using the century-long historical record of the times of light minimum, we analysed the cyclic period change in the Algol binary WW Dra. It is found that the orbital period of the binary shows a ~112.2-yr cyclic variation with an amplitude of ~0.1977d. The cyclic oscillation can be attributed to the LTTE by means of a third body with a mass no less than 6.43Msolar. However, no spectral lines of the third body were discovered, indicating that it may be a candidate black hole. The third body is orbiting the binary at a distance closer than 14.4 au and may play an important role in the evolution of this system.

Starspots on V711 Tauri /HR 1099/

NASA Astrophysics Data System (ADS)

Dorren, J. D.; Siah, M. J.; Guinan, E. F.; McCook, G. P.

1981-04-01

Hα (λ6563) intermediate- and narrowband light curves of the RS CVn-type binary system V711 Tau (HR 1099) were obtained in 1977-1978 at Biruni Observatory and in 1977-1978 and late 1979 at Villanova Observatory, where a λ7790 light curve was also obtained in 1977-1978. The light curves are quasisinusoidal, with a period approximately equal to the spectroscopic period. A significant change in the λ6585 light curve occurred between the two observing seasons, with an increase in amplitude from 0.075 to 0.125 mag, a change of shape, and an advance in the phases of maximum and minimum light by 0.3 phase. Flaring activity in Hα was observed, on time scales from minutes to days. We fitted our light curves and V-band light curves obtained at the same time using the starspot model of Torres and Ferraz Mello. We the observed light variations are due to the synchronous rotation of spots on the heavier member of the binary system, which has been shown to be the chromospherically active star. The orbital inclination was assumed to be 35°. Radiant fluxes were taken from spectrophotometric tables. Owing to the broad wavelength coverage in 1977-1978, it was possible to determine the spot temperature to be ˜1800 K cooler than the photosphere, and hence to fix the spot area. A simple model with two circular spots of 26° radius at the same latitude, +48°, adequately reproduces the 1977-1978 light curves. The 1979 observations can be reproduced in detail by a model with two slightly larger circular spots of 31°.5 radius at latitude +15°. The spots cover about 14% of the total stellar surface in 1979. The fits also provide an explanation of the presence of an observed phase dependence in the Hα emission in 1979 but not in 1977-1978. There is a strong suggestion that a spot cycle is in progress in V711 Tau.

Spectroscopic investigation of stars on the lower main sequence

NASA Astrophysics Data System (ADS)

Mishenina, T. V.; Soubiran, C.; Bienaymé, O.; Korotin, S. A.; Belik, S. I.; Usenko, I. A.; Kovtyukh, V. V.

2008-10-01

Aims: The aim of this paper is to provide fundamental parameters and abundances with a high accuracy for a large sample of cool main sequence stars. This study is part of wider project, in which the metallicity distribution of the local thin disc is investigated from a complete sample of G and K dwarfs within 25 pc. Methods: The stars were observed at high resolution and a high signal-to-noise ratio with the ELODIE echelle spectrograph. The V sin i were obtained with a calibration of the cross-correlation function. Effective temperatures were estimated by the line depth ratio method. Surface gravities (log g) were determined by two methods: parallaxes and ionization balance of iron. The Mg and Na abundances were derived using a non-LTE approximation. Abundances of other elements were obtained by measuring equivalent widths. Results: Rotational velocities, atmospheric parameters (T_eff, log g, [Fe/H], V_t), and Li, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Co, Ni, and Zn abundances are provided for 131 stars. Among them, more than 30 stars are active stars with a fraction of BY Dra and RS CVn type stars for which spectral peculiarities were investigated. We find the mean abundances of the majority of elements in active and nonactive stars to be similar, except for Li, and possibly for Zn and Co. The lithium is reliably detected in 54% of active stars but only in 20% of nonactive stars. No correlation is found between Li abundances and rotational velocities. A possible anticorrelation of log A(Li) with the index of chromospheric activity GrandS is observed. Conclusions: Active and nonactive cool dwarfs show similar dependencies of most elemental ratios vs. [Fe/H]. This allows us to use such abundance ratios to study the chemical and dynamical evolution of the Galaxy. Among active stars, no clear correlation has been found between different indicators of activity for our sample stars. Based on spectra collected with the ELODIE spectrograph at the 1.93-m telescope of the Observatoire de Haute Provence (France). Tables A.1-A3 are 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/489/923

Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.

PubMed

Dobrinas, Maria; Cornuz, Jacques; Eap, Chin B

2013-05-01

There is a high interindividual variability in cytochrome P4501A2 (CYP1A2) activity and in its inducibility by smoking, only poorly explained by known CYP1A2 polymorphisms. We aimed to study the contribution of other regulatory pathways, including transcription factors and nuclear receptors, toward this variability. CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of them who were abstinent for 4 weeks. Participants were genotyped for 22 polymorphisms in 12 genes. A significant influence on CYP1A2 inducibility was observed for the NR1I3 rs2502815 (P=0.0026), rs4073054 (P=0.029), NR2B1 rs3818740 (P=0.0045), rs3132297 (P=0.036), AhR rs2282885 (P=0.040), rs2066853 (P=0.019), NR1I1 rs2228570 (P=0.037), and NR1I2 rs1523130 (P=0.044) polymorphisms. Among these, the NR1I3 rs2502815 (P=0.0045), rs4073054 (P=0.048), and NR2B1 rs3818740 (P=0.031) also influenced CYP1A2 basal activity. This is the first in-vivo demonstration of the influence of genes involved in CYP1A2 regulatory pathways on its basal activity and inducibility by smoking. These results need to be confirmed by other studies.

Observations, Roche Lobe Analysis, and Period Study of the Eclipsing Contact Binary System GM Canum Venaticorum

NASA Astrophysics Data System (ADS)

Alton, K. B.; Nelson, R. H.

2018-06-01

GM CVn is an eclipsing W UMa binary system (P = 0.366984 d) which has been largely neglected since its variability was first detected during the ROTSE campaign (1999-2000). Other than a single unfiltered light curve (LC) no other photometric data have been published. LC data collected in three bandpasses (B, V, and Rc) at UnderOak Observatory (UO) produced three new times of minimum for GM CVn. These along with other eclipse timings from the literature were used to update the linear ephemeris. Roche modeling to produce synthetic LC fits to the observed data was accomplished using binary maker 3, wdwint56a, and phoebe v.31a. Newly acquired radial velocity data were pivotal to defining the absolute and geometric parameters for this partially eclipsing binary system. An unspotted solution achieved the best Roche model fits for the multi-color LCs collected in 2013.

A novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator RS9 attenuates brain injury after ischemia reperfusion in mice.

PubMed

Yamauchi, Keita; Nakano, Yusuke; Imai, Takahiko; Takagi, Toshinori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Iwama, Toru; Hara, Hideaki

2016-10-01

Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique. RS9 has been reported to lead to higher Nrf2 activation and less cytotoxicity than BARD. In this study, we investigated the effects of RS9 on IRI. Mice were intraperitoneally treated immediately after 2h of transient middle cerebral artery occlusion (MCAO) with a vehicle solution or 0.2mg/kg of RS9. Post-onset treatment of RS9 attenuated the infarct volume and improved neurological deficits 22h after reperfusion. RS9 activated Nrf2 2 and 6h after reperfusion and activated heme oxygenase-1 at 6 and 22h after reperfusion. RS9 also attenuated the phosphorylation of NF-κB p65 2 and 6h after reperfusion. Finally, RS9 improved the survival rate and neurological deficits 7days after MCAO. Our results suggest that the activation of Nrf2 by RS9 has a neuroprotective effect, mediated by attenuating both oxidative stress and neuroinflammation, and that RS9 is an effective therapeutic candidate for the treatment of IRI. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Yeast Mitochondrial Leucyl-tRNA Synthetase CP1 Domain Has Functionally Diverged to Accommodate RNA Splicing at Expense of Hydrolytic Editing*

PubMed Central

Sarkar, Jaya; Poruri, Kiranmai; Boniecki, Michal T.; McTavish, Katherine K.; Martinis, Susan A.

2012-01-01

The yeast mitochondrial leucyl-tRNA synthetase (ymLeuRS) performs dual essential roles in group I intron splicing and protein synthesis. A specific LeuRS domain called CP1 is responsible for clearing noncognate amino acids that are misactivated during aminoacylation. The ymLeuRS CP1 domain also plays a critical role in splicing. Herein, the ymLeuRS CP1 domain was isolated from the full-length enzyme and was active in RNA splicing in vitro. Unlike its Escherichia coli LeuRS CP1 domain counterpart, it failed to significantly hydrolyze misaminoacylated tRNALeu. In addition and in stark contrast to the yeast domain, the editing-active E. coli LeuRS CP1 domain failed to recapitulate the splicing activity of the full-length E. coli enzyme. Although LeuRS-dependent splicing activity is rooted in an ancient adaptation for its aminoacylation activity, these results suggest that the ymLeuRS has functionally diverged to confer a robust splicing activity. This adaptation could have come at some expense to the protein's housekeeping role in aminoacylation and editing. PMID:22383526

Transition Fracture Toughness Characterization of Eurofer 97 Steel using Pre-Cracked Miniature Multi-notch Bend Bar Specimens

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

Chen, Xiang; Sokolov, Mikhail A.; Linton, Kory D.

In this report, we present the feasibility study of using pre-cracked miniature multi-notch bend bar specimens (M4CVN) with a dimension of 45mm (length) x 3.3mm (width) x 1.65mm (thickness) to characterize the transition fracture toughness of Eurofer97 based on the ASTM E1921 Master Curve method. From literature survey results, we did not find any obvious specimen size effects on the measured fracture toughness of unirradiated Eurofer97. Nonetheless, in order to exclude the specimen size effect on the measured fracture toughness of neutron irradiated Eurofer97, comparison of results obtained from larger size specimens with those from smaller size specimens after neutronmore » irradiation is necessary, which is not practical and can be formidably expensive. However, limited literature results indicate that the transition fracture toughness of Eurofer97 obtained from different specimen sizes and geometries followed the similar irradiation embrittlement trend. We then described the newly designed experimental setup to be used for testing neutron irradiated Eurofer97 pre-cracked M4CVN bend bars in the hot cell. We recently used the same setup for testing neutron irradiated F82H pre-cracked miniature multi-notch bend bars with great success. Considering the similarity in materials, specimen types, and the nature of tests between Eurofer97 and F82H, we believe the newly designed experimental setup can be used successfully in fracture toughness testing of Eurofer97 pre-cracked M4CVN specimens.« less

Color Vision and the Railways: Part 1. The Railway LED Lantern Test.

PubMed

Dain, Stephen J; Casolin, Armand; Long, Jennifer; Hilmi, Mohd Radzi

2015-02-01

Lantern tests and practical tests are often used in the assessment of prospective railway employees. The lantern tests rarely embody the actual colors used in signaling on the railways. Practical tests have a number of problems, most notably consistency of application and practicability. This work was carried out to provide the Railway LED Lantern Test (RLLT) as a validated method of assessing the color vision of railway workers. The RLLT, a simulated practical test using the same LEDs (light-emitting diodes) as are used in modern railway signals, was developed. It was tested on 46 color vision-normal (CVN) and 37 color vision-deficient (CVD) subjects. A modified prototype was then tested on 106 CVN subjects. All 106 CVN subjects and most mildly affected CVD subjects passed the modified lantern at 3 m. At 6 m, 1 of the 106 normal color vision subjects failed by missing a single red light. All the CVD subjects failed. The RLLT carried out at 3 m allowed mildly affected CVD subjects to pass and demonstrate adequate color vision for the less demanding railway tasks. Carried out at 6 m, it essentially reinforced normal color vision as the standard. The RLLT is a simply administered test that has a direct link to the actual visual task of the rail worker. The RLLT lantern has been adopted as an approved test in the Australian National Standard for Health Assessment of Rail Safety Workers in place of a practical test. It has the potential to be a valid part of any railway color vision standard.

Participation of inositol trisphosphate and ryanodine receptors in Bufo arenarum oocyte activation.

PubMed

Ajmat, M T; Bonilla, F; Zelarayán, L; Bühler, M I

2011-05-01

Calcium is considered the most important second messenger at fertilization. Transient release from intracellular stores is modulated through both agonist-gated channels, IP₃Rs and RyRs, which can be found individually or together depending on the oocyte species. Using the four commonly used compounds (thimerosal, caffeine, heparin and ruthenium red), we investigated the existence and interdependence of both IP₃Rs and RyRs in mature Bufo arenarum oocytes. We found that caffeine, a well known specific RyRs agonist, was able to trigger oocyte activation in a dose-dependent manner. Microinjection of 10 mM caffeine showed 100% of oocytes exhibiting characteristic morphological criteria of egg activation. Ruthenium red, the specific RyR blocker, was able to inhibit oocyte activation induced either by sperm or caffeine. Our present findings provide the first reported evidence of the existence of RyR in frogs. We further explored the relationship between IP₃Rs and RyRs in B. arenarum oocytes by exposing them to the agonists of one class after injecting a blocker of the other class of receptor. We found that thimerosal overcame the inhibitory effect of RyR on oocyte activation, indicating that IP₃Rs function as independent receptors. In contrast, previous injection of heparin delayed caffeine-induced calcium release, revealing a relative dependence of RyRs on functional IP₃Rs, probably through a CICR mechanism. Both receptors play a role in Ca²+ release mechanisms although their relative contribution to the activation process is unclear.

Another look at AM Herculis - radio-astrometric campaign with the e-EVN at 6 cm

NASA Astrophysics Data System (ADS)

Gawroński, M. P.; Goździewski, K.; Katarzyński, K.; Rycyk, G.

2018-03-01

We conducted radio-interferometric observations of the well-known binary cataclysmic system AM Herculis. This particular system is formed from a magnetic white dwarf (primary) and a red dwarf (secondary), and it is the prototype of so-called polars. Our observations were conducted with the European VLBI Network (EVN) in e-EVN mode at 5 GHz. We obtained six astrometric measurements spanning 1 yr, which make it possible to update the annual parallax for this system with the best precision to date (π = 11.29 ± 0.08 mas), which is equivalent to a distance of 88.6 ± 0.6 pc. The system was observed mostly in the quiescent phase (visual magnitude mv ˜ 15.3), when the radio emission was at the level of about 300 μJy. Our analysis suggests that the radio flux of AM Herculis is modulated with the orbital motion. Such specific properties of the radiation can be explained using an emission mechanism like the scenario proposed for V471 Tau and, in general, for RS CVn-type stars. In this scenario, the radio emission arises near the surface of the red dwarf, where the global magnetic field strength may reach a few kG. We argue that the quiescent radio emission distinguishes AM Herculis and AR Ursae Majoris (a second known persistent radio polar) from other polars, which are systems with a magnetized secondary star.

Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus

PubMed Central

Ericson, Megan E.; Subramanian, Chitra; Frank, Matthew W.

2017-01-01

ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. PMID:28765222

Magnetic field structure in single late-type giants: the effectively single giant V390 Aurigae

NASA Astrophysics Data System (ADS)

Konstantinova-Antova, R.; Aurière, M.; Petit, P.; Charbonnel, C.; Tsvetkova, S.; Lèbre, A.; Bogdanovski, R.

2012-05-01

Aims: We have studied the active giant V390 Aur using spectropolarimetry to obtain direct and simultaneous measurements of the magnetic field and the activity indicators to obtain a precise insight of its activity. Methods: We used the spectropolarimeter NARVAL at the Bernard Lyot Telescope (Observatoire du Pic du Midi, France) to obtain a series of Stokes I and Stokes V profiles. Using the least-squares deconvolution (LSD) technique we were able to detect the Zeeman signature of the magnetic field in each of our 13 observations and to measure its longitudinal component. Using the wide wavelength range of the spectra we were able to monitor the CaII K&H and IR triplet, as well as the Hα lines, which are activity indicators. To reconstruct the magnetic field geometry of V390 Aur on the basis of modelling the Stokes V profiles, we applied the Zeeman Doppler imaging (ZDI) inversion method and present a map for the magnetic field. Based on the obtained spectra, we also refined the fundamental parameters of the star and the Li abundance using MARCS model atmospheres. Results: The ZDI revealed a structure in the radial magnetic field consisting of a polar magnetic spot of positive polarity and several negative spots at lower latitude. A high latitude belt is present on the azimuthal field map, indicative of a toroidal field close to the surface. Similar features are observed in some RS CVn and FK Com -type stars. It was found that the photometric period cannot fit the behaviour of the activity indicators formed in the chromosphere. Their behaviour suggests slower rotation compared to the photosphere, but our dataset is too short for us to be able to estimate their exact periods. All these results can be explained in terms of an α - ω dynamo operation, taking into account the stellar structure and rotation properties of V390 Aur that we studied with up-to-date stellar models computed at solar metallicity with the code STAREVOL. The calculated Rossby number also points to a very efficient dynamo. Based on data obtained using the Bernard Lyot Telescope at Observatoire du Pic du Midi, CNRS and Université Paul Sabatier, France.

Two Major Medicinal Honeys Have Different Mechanisms of Bactericidal Activity

PubMed Central

Kwakman, Paulus H. S.; te Velde, Anje A.; de Boer, Leonie; Vandenbroucke-Grauls, Christina M. J. E.; Zaat, Sebastian A. J.

2011-01-01

Honey is increasingly valued for its antibacterial activity, but knowledge regarding the mechanism of action is still incomplete. We assessed the bactericidal activity and mechanism of action of Revamil® source (RS) honey and manuka honey, the sources of two major medical-grade honeys. RS honey killed Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa within 2 hours, whereas manuka honey had such rapid activity only against B. subtilis. After 24 hours of incubation, both honeys killed all tested bacteria, including methicillin-resistant Staphylococcus aureus, but manuka honey retained activity up to higher dilutions than RS honey. Bee defensin-1 and H2O2 were the major factors involved in rapid bactericidal activity of RS honey. These factors were absent in manuka honey, but this honey contained 44-fold higher concentrations of methylglyoxal than RS honey. Methylglyoxal was a major bactericidal factor in manuka honey, but after neutralization of this compound manuka honey retained bactericidal activity due to several unknown factors. RS and manuka honey have highly distinct compositions of bactericidal factors, resulting in large differences in bactericidal activity. PMID:21394213

Preventive effect of resistant starch on activated carbon-induced constipation in mice

PubMed Central

QIAN, YU; ZHAO, XIN; KAN, JIANQUAN

2013-01-01

The aim of this study was to investigate the effects of resistant starch (RS) on activated carbon-induced constipation in ICR mice. ICR mice were fed on diet containing 15% RS of type RS2, RS3 or RS4 for 9 days. Gastrointestinal transit, defecation time and intestinal tissue histopathological sections, as well as motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were used to evaluate the preventive effects of RS on constipation. Bisacodyl, a laxative drug, was used as a positive control. The time to the first black stool defecation for normal, control, bisacodyl-treated (100 mg/kg, oral administration) and RS2-, RS3- and RS4-treated mice was 78, 208, 109, 181, 144 and 173 min, respectively. Following the consumption of RS2, RS3 and RS4 or the oral administration of bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 37.7, 52.1, 39.3 and 87.3%, respectively, of the transit in normal mice, respectively. Histopathological sections of intestinal tissue also underscored the protective effect of RS3. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with RS compared with those in the untreated control mice (P<0.05). These results demonstrate that RS has preventive effects on mouse constipation and RS3 demonstrated the best functional activity. PMID:23935751

Expression and enzymatic activity of phenylalanine ammonia-lyase and p-coumarate 3-hydroxylase in mango (Mangifera indica 'Ataulfo') during ripening.

PubMed

Palafox-Carlos, H; Contreras-Vergara, C A; Muhlia-Almazán, A; Islas-Osuna, M A; González-Aguilar, G A

2014-05-16

Phenylalanine ammonia lyase (PAL) and p-coumarate 3-hydroxylase (C3H) are key enzymes in the phenylpropanoid pathway. The relative expression of PAL and C3H was evaluated in mango fruit cultivar 'Ataulfo' in four ripening stages (RS1, RS2, RS3, and RS4) by quantitative polymerase chain reaction. In addition, enzyme activity of PAL and C3H was determined in mango fruits during ripening. The PAL levels were downregulated at the RS2 and RS3 stages, while C3H levels were upregulated in fruits only at RS3. The enzyme activity of PAL followed a pattern that was different from that of the PAL expression, thus suggesting regulation at several levels. For C3H, a regulation at the transcriptional level is suggested because a similar pattern was revealed by its activity and transcript level. In this study, the complexity of secondary metabolite biosynthesis regulation is emphasized because PAL and C3H enzymes are involved in the biosynthesis of several secondary metabolites that are active during all mango ripening stages.

Two non-redundant fragments in the N-terminal peptide of human cytosolic methionyl-tRNA synthetase were indispensable for the multi-synthetase complex incorporation and enzyme activity.

PubMed

He, Ran; Zu, Li-Dong; Yao, Peng; Chen, Xin; Wang, En-Duo

2009-02-01

In human cytoplasm, nine aminoacyl-tRNA synthetases (aaRSs) and three protein factors form a multi-synthetase complex (MSC). Human cytosolic methionyl-tRNA synthetase (hcMetRS) is a component of the MSC. Sequence alignment revealed that hcMetRS has an N-terminal extension of 267 amino acid residues. This extension can be divided into three sub-domains: GST-like, GN, and GC sub-domains. The effect of each sub-domain in the N-terminal extension of hcMetRS on enzymatic activity and incorporation into the MSC was studied. The results of cellular assay showed that the GST-like sub-domain was responsible for the incorporation of hcMetRS into the MSC. The entire N-terminal extension of hcMetRS is indispensable for the enzymatic activity. Deletion mutagenesis revealed that a seven-amino acid motif within the sub-domain GC was important for the activity of amino acid activation. A conserved proline residue within the seven-amino acid motif was crucial, while the other six residues were moderately important for the amino acid activation activity. Thus, the last 15 residues of previously defined N-terminal extension of hcMetRS was a part of the catalytic domain; whereas the first 252 residues of hcMetRS constitute the N-terminal extended domain of hcMetRS. The formerly defined N-terminal extension of hcMetRS possesses two functions of two different domains.

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism.

PubMed

Tansey, Katherine E; Hill, Matthew J; Cochrane, Lynne E; Gill, Michael; Anney, Richard Jl; Gallagher, Louise

2011-03-31

Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of AVPR1A in variable gene expression and social behaviour. We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity

PubMed Central

Wang, Danxin; Poi, Ming J.; Sun, Xiaochun; Gaedigk, Andrea; Leeder, J. Steven; Sadee, Wolfgang

2014-01-01

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically used drugs. Genetic polymorphisms cause substantial variation in CYP2D6 activity and serve as biomarkers guiding drug therapy. However, genotype–phenotype relationships remain ambiguous except for poor metabolizers carrying null alleles, suggesting the presence of yet unknown genetic variants. Searching for regulatory CYP2D6 polymorphisms, we find that a SNP defining the CYP2D6*2 allele, rs16947 [R296C, 17–60% minor allele frequency (MAF)], previously thought to convey normal activity, alters exon 6 splicing, thereby reducing CYP2D6 expression at least 2-fold. In addition, two completely linked SNPs (rs5758550/rs133333, MAF 13–42%) increase CYP2D6 transcription more than 2-fold, located in a distant downstream enhancer region (>100 kb) that interacts with the CYP2D6 promoter. In high linkage disequilibrium (LD) with each other, rs16947 and the enhancer SNPs form haplotypes that affect CYP2D6 enzyme activity in vivo. In a pediatric cohort of 164 individuals, rs16947 alone (minor haplotype frequency 28%) was associated with reduced CYP2D6 metabolic activity (measured as dextromethorphan/metabolite ratios), whereas rs5758550/rs133333 alone (frequency 3%) resulted in increased CYP2D6 activity, while haplotypes containing both rs16947 and rs5758550/rs133333 were similar to the wild-type. Other alleles used in biomarker panels carrying these variants such as CYP2D6*41 require re-evaluation of independent effects on CYP2D6 activity. The occurrence of two regulatory variants of high frequency and in high LD, residing on a long haplotype, highlights the importance of gene architecture, likely shaped by evolutionary selection pressures, in determining activity of encoded proteins. PMID:23985325

Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus.

PubMed

Ericson, Megan E; Subramanian, Chitra; Frank, Matthew W; Rock, Charles O

2017-08-01

The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus , but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. IMPORTANCE The SaeRS two-component system is a master transcriptional activator of virulence factor production in response to the host environment in S. aureus , and strains lacking FA kinase have severely attenuated SaeRS-dependent virulence factor transcription. FA kinase is required for the activation of exogenous FAs, and it plays a role in cellular lipid homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway. Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain, and the FAs which accumulate in FA kinase knockout strains are potent inhibitors of SaeS-dependent signaling. This work identifies FAs as physiological effectors for the SaeRS system and reveals a connection between cellular lipid homeostasis and the regulation of virulence factor transcription. FA kinase is widely distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in these organisms. Copyright © 2017 Ericson et al.

Genetic Variation Affects C-Reactive Protein Elevations in Crohn's Disease.

PubMed

Moran, Christopher J; Kaplan, Jess L; Winter, Harland S

2018-04-28

C-reactive protein (CRP) is a serum marker that is used to measure disease activity in Crohn's disease (CD). However, a subset of CD patients have normal CRP during flares. In rheumatoid arthritis and lupus, genetic variants can restrict CRP elevations during flares. This study sought to determine if common CRP genetic variants affect CRP values during active CD. Subjects with CD who participated in the Partners HealthCare BioBank were genotyped for 5 common CRP genetic variants (rs2794520, rs3122012, rs3093077, rs2808635, and rs1800947). Medical records were reviewed to determine disease activity and the highest CRP value during active CD. CRP values during active infection or malignancy at the time of the test were excluded. CRP values were compared by genotype using the Mann-Whitney test. The study included 199 subjects with active CD (21 to 86 years of age). Subjects with the rs2794520 TT genotype had a lower CRP than subjects with the CC genotype (58.3 mg/L vs 28.4 mg/L, P = 0.008). Subjects with the rs1800947 CG genotype had a lower CRP than those with the CC genotype (54.3 mg/L vs 22.4 mg/L, P < 0.0001); 41.6% of TT subjects had a normal CRP compared with 24.1% of CT subjects and 16.5% of CC subjects (P = 0.041). This study demonstrates that rs2794520 and rs1800947 are associated with a restriction of CRP elevations during active CD. While CRP is typically a reliable biomarker in CD, there is a subset of CD patients with a genetically determined restriction of CRP in whom other disease markers should be utilized.

Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults.

PubMed

Drescher, Olivia; Dewailly, Eric; Diorio, Caroline; Ouellet, Nathalie; Sidi, Elhadji Anassour Laouan; Abdous, Belkacem; Valera, Beatriz; Ayotte, Pierre

2014-11-01

There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (-162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the -108T allele (P=0.009). Our results suggest a gene-environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.

Photometric and Spectroscopic Study of the Delta Scuti Stars FH Cam, CU CVn and CC Lyn

NASA Astrophysics Data System (ADS)

Conidis, G. J.; Gazeas, K. D.; Capobianco, C. C.; Ogloza, W.

2010-06-01

Three short period (P ˜ 1 day) variable stars from the Hipparcos catalogue targets were observed after suspected misclassification as Beta Lyr eclipsing systems (Perryman et al. 1997), as no secondary component had been noticed in the inspection of their Broadening Functions (BFs) (Rucinski 2002). FH Cam is found to be a multiple star system with a member exhibiting Delta Scuti behaviour. The dominant pulsation frequency is found to be 7.3411 ± 0.0002 c/d, which corresponds to a pulsation mode of l ≤ 1. We confirmed the pulsations of CU CVn using photometric observations and found a pulsation frequency of 14.7626 ± 0.0250 c/d, which is in agreement with the period given in literature. CC Lyn is a non-eclipsing visual binary (CCDM J07359+4302AB), the brighter component (A) is found to be a multi-mode Delta Scuti pulsator, with pulsation frequencies of 5.6402 ± 0.0004 c/d and 7.3368 ± 0.0005 c/d.

Procedure improves line pipe Charpy test interpretation

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

Rosenfeld, M.J.

1997-04-14

The Charpy V-notch (CVN) impact test is a method of characterizing a line-pipe material`s notch toughness and resistance to fracture growth. Although CVN testing of line pipe material is routine, test results are sometimes misinterpreted because of specimen size and load rate on actual toughness transition behavior. These effects are readily accounted for by a simple mathematical procedure, offered here, which enables extrapolation of the full-scale transition curve from as little as a single subsize specimen test. This procedure is useful when the toughness transition curve is incomplete or nonexistent. Toughness data may be incomplete because the API 5L toughnessmore » test establishes minimum performance at a single temperature, which does not reveal the full transition curve. Toughness data may be nonexistent because the first requirements for toughness testing of line pipe appeared in the 16th Edition of API 5LX in 1969, and those requirements remain at the option of the purchaser today.« less

Specimen size effects on ductile?brittle transition temperature in Charpy impact testing

NASA Astrophysics Data System (ADS)

Kurishita, H.; Yamamoto, T.; Narui, M.; Suwarno, H.; Yoshitake, T.; Yano, Y.; Yamazaki, M.; Matsui, H.

2004-08-01

One key issue for small specimen test techniques is to clarify specimen size effects on test results. In consideration of size effects on determining the ductile-to-brittle transition temperature (DBTT) in Charpy impact testing, a method to evaluate the plastic constraint loss for differently sized Charpy V-notch (CVN) specimens is proposed and applied to a ferritic-martensitic steel, 2WFK, developed by JNC. In the method, a constraint factor, α, that is an index of the plastic constraint is defined as α=σ ∗/σ y∗. Here, σ ∗ is the critical cleavage fracture stress which is a material constant and σ y∗ is the uniaxial yield stress at the DBTT at the strain rate generated in the Charpy impact test. The procedures for evaluating each of σ ∗ and σ y∗ are described and a result of σ ∗ and σ y∗, thus the value of α, is presented for different types of miniaturized and full-sized CVN specimens of 2WFK.

Exploiting Uniformly 13C-Labeled Carbohydrates for Probing Carbohydrate-Protein Interactions by NMR Spectroscopy.

PubMed

Nestor, Gustav; Anderson, Taigh; Oscarson, Stefan; Gronenborn, Angela M

2017-05-03

NMR of a uniformly 13 C-labeled carbohydrate was used to elucidate the atomic details of a sugar-protein complex. The structure of the 13 C-labeled Manα(1-2)Manα(1-2)ManαOMe trisaccharide ligand, when bound to cyanovirin-N (CV-N), was characterized and revealed that in the complex the glycosidic linkage torsion angles between the two reducing-end mannoses are different from the free trisaccharide. Distances within the carbohydrate were employed for conformational analysis, and NOE-based distance mapping between sugar and protein revealed that Manα(1-2)Manα(1-2)ManαOMe is bound more intimately with its two reducing-end mannoses into the domain A binding site of CV-N than with the nonreducing end unit. Taking advantage of the 13 C spectral dispersion of 13 C-labeled carbohydrates in isotope-filtered experiments is a versatile means for a simultaneous mapping of the binding interactions on both, the carbohydrate and the protein.

Constraining the Physics of AM Canum Venaticorum Systems with the Accretion Disk Instability Model

NASA Technical Reports Server (NTRS)

Cannizzo, John K.; Nelemans, Gijs

2015-01-01

Recent work by Levitan et al. has expanded the long-term photometric database for AM CVn stars. In particular, their outburst properties are well correlated with orbital period and allow constraints to be placed on the secular mass transfer rate between secondary and primary if one adopts the disk instability model for the outbursts. We use the observed range of outbursting behavior for AM CVn systems as a function of orbital period to place a constraint on mass transfer rate versus orbital period. We infer a rate approximately 5 x 10(exp -9) solar mass yr(exp -1) ((P(sub orb)/1000 s)(exp -5.2)). We show that the functional form so obtained is consistent with the recurrence time-orbital period relation found by Levitan et al. using a simple theory for the recurrence time. Also, we predict that their steep dependence of outburst duration on orbital period will flatten considerably once the longer orbital period systems have more complete observations.

Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus.

PubMed

Kim, Hye-Hyun; Lee, Kyu-Hee; Lee, Doyun; Han, Young-Eun; Lee, Suk-Ho; Sohn, Jong-Woo; Ho, Won-Kyung

2015-04-22

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca(2+) signals that are induced by AMPA-mediated depolarization and L-type Ca(2+) channel activation. Finally, we found that PLC and L-type Ca(2+) channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca(2+) influx via the L-type Ca(2+) channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus. Copyright © 2015 the authors 0270-6474/15/356401-12$15.00/0.

Genetic and Functional Assessment of the Role of the rs13431652-A and rs573225-A Alleles in the G6PC2 Promoter That Are Strongly Associated With Elevated Fasting Glucose Levels

PubMed Central

Bouatia-Naji, Nabila; Bonnefond, Amélie; Baerenwald, Devin A.; Marchand, Marion; Bugliani, Marco; Marchetti, Piero; Pattou, François; Printz, Richard L.; Flemming, Brian P.; Umunakwe, Obi C.; Conley, Nicholas L.; Vaxillaire, Martine; Lantieri, Olivier; Balkau, Beverley; Marre, Michel; Lévy-Marchal, Claire; Elliott, Paul; Jarvelin, Marjo-Riitta; Meyre, David; Dina, Christian; Oeser, James K.; Froguel, Philippe; O'Brien, Richard M.

2010-01-01

OBJECTIVE Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal. RESEARCH DESIGN AND METHODS We genotyped 9,532 normal FPG participants (FPG <6.1 mmol/l) for three G6PC2 SNPs, rs13431652 (distal promoter), rs573225 (proximal promoter), rs560887 (3rd intron). We used regression analyses adjusted for age, sex, and BMI to assess the association with FPG and haplotype analyses to assess comparative SNP contributions. Fusion gene and gel retardation analyses characterized the effect of rs13431652 and rs573225 on G6PC2 promoter activity and transcription factor binding. RESULTS Genetic analyses provide evidence for a strong contribution of the promoter SNPs to FPG variability at the G6PC2 locus (rs13431652: β = 0.075, P = 3.6 × 10−35; rs573225 β = 0.073 P = 3.6 × 10−34), in addition to rs560887 (β = 0.071, P = 1.2 × 10−31). The rs13431652-A and rs573225-A alleles promote increased NF-Y and Foxa2 binding, respectively. The rs13431652-A allele is associated with increased FPG and elevated promoter activity, consistent with the function of G6PC2 in pancreatic islets. In contrast, the rs573225-A allele is associated with elevated FPG but reduced promoter activity. CONCLUSIONS Genetic and in situ functional data support a potential role for rs13431652, but not rs573225, as a causative SNP linking G6PC2 to variations in FPG, though a causative role for rs573225 in vivo cannot be ruled out. PMID:20622168

Structural Switch of Lysyl-tRNA Synthetase Between Translation and Transcription

PubMed Central

Ofir-Birin, Yifat; Fang, Pengfei; Bennett, Steven P.; Zhang, Hui-Min; Wang, Jing; Rachmin, Inbal; Shapiro, Ryan; Song, Jing; Dagan, Arie; Pozo, Jorge; Kim, Sunghoon; Marshall, Alan G.; Schimmel, Paul; Yang, Xiang-Lei; Nechushtan, Hovav; Razin, Ehud; Guo, Min

2013-01-01

SUMMARY Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207-phosphorylation provokes a new conformer of LysRS that inactivates its translational, but activates its transcriptional function. The crystal structure of an MSC sub-complex established that LysRS is held in the MSC by binding to the N-terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap4A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription. PMID:23159739

The Fu Foundation School of Engineering & Applied Science - Columbia

Science.gov Websites

Room Reservation Contact Us Admissions - Undergraduate Admissions - Graduate Office of the Dean Alumni Partnerships Distance Learning (CVN) Current Students Undergraduate Graduate Career Development Distance GradZone Faculty Search Alumni Programs and Events Benefits & Services Get Involved Giving to Columbia

Polymorphisms of the peroxisome proliferator-activated receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus.

PubMed

Kruzliak, Peter; Haley, Andreana P; Starcevic, Jovana Nikolajevic; Gaspar, Ludovit; Petrovic, Daniel

2015-04-28

The aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with obesity indexes (BMI, waist circumference) in subjects with type 2 diabetes mellitus (T2DM) in Caucasian population. The second aim was to find an association of both polymorphisms with T2DM. Two exonic SNPs of both genes rs1801282 of the PPAR-γ gene and rs8192673 of the PGC-1α gene) were genotyped in 881 unrelated Slovene subjects (Caucasians) with T2DM and in 348 subjects without T2DM (control subjects). Female homozygotes with the CC genotype of the rs8192673 had higher waist circumference in comparison with subjects with other genotypes. Homozygotes (females, males) with wild allele (Pro) of the rs1801282 (Pro12Ala polymorphism) had higher waist circumference in comparison with subjects with other genotypes. In the study, there were no differences in the distributions of the rs8192673 and the rs1801282 genotypes between patients with T2DM and controls. Linear regression analyses for both polymorphisms were performed and demonstrated an independent effect of the rs1801282 of the PPAR-γ on waist circumference in subjects with T2DM, whereas an independent effect on waist circumference was not demonstrated for the rs8192673 of the PGC-1α gene. In a large sample of the Caucasians the rs8192673 of the PGC-1α gene and the rs1801282 of the PPAR-γ gene were associated with waist circumference in subjects with T2DM.

Magnetic Doppler imaging of α2 Canum Venaticorum in all four Stokes parameters. Unveiling the hidden complexity of stellar magnetic fields

NASA Astrophysics Data System (ADS)

Kochukhov, O.; Wade, G. A.

2010-04-01

Context. Strong organized magnetic fields have been studied in the upper main sequence chemically peculiar stars for more than half a century. However, only recently have observational methods and numerical techniques become sufficiently mature to allow us to record and interpret high-resolution four Stokes parameter spectra, leading to the first assumption-free magnetic field models of these stars. Aims: Here we present a detailed magnetic Doppler imaging analysis of the spectropolarimetric observations of the prototypical magnetic Ap star α2 CVn. This is the second star for which the magnetic field topology and horizontal chemical abundance inhomogeneities have been inferred directly from phase-resolved observations of line profiles in all four Stokes parameters, free from the traditional assumption of a low-order multipolar field geometry. Methods: We interpret the rotational modulation of the circular and linear polarization profiles of the strong Fe II and Cr II lines in the spectra of α2 CVn recorded with the MuSiCoS spectropolarimeter. The surface abundance distributions of the two chemical elements and a full vector map of the stellar magnetic field are reconstructed in a self-consistent inversion using our state-of-the-art magnetic Doppler imaging code Invers10. Results: We succeeded in reproducing most of the details of the available spectropolarimetric observations of α2 CVn with a magnetic map which combines a global dipolar-like field topology with localized spots of higher field intensity. We demonstrate that these small-scale magnetic structures are inevitably required to fit the linear polarization spectra; however, their presence cannot be inferred from the Stokes I and V observations alone. We also found high-contrast surface distributions of Fe and Cr, with both elements showing abundance minima in the region of weaker and topologically simpler magnetic field. Conclusions: Our magnetic Doppler imaging analysis of α2 CVn and previous results for 53 Cam support the view that the upper main sequence stars can harbour fairly complex surface magnetic fields which resemble oblique dipoles only at the largest spatial scales. Spectra in all four Stokes parameters are absolutely essential to unveil and meaningfully characterize this field complexity in Ap stars. We therefore suggest that understanding magnetism of stars in other parts of the H-R diagram is similarly incomplete without investigation of their linear polarization spectra. Based on data obtained using the Télescope Bernard Lyot at Observatoire du Pic du Midi.

Dissociating retrieval success from incidental encoding activity during emotional memory retrieval, in the medial temporal lobe

PubMed Central

Shafer, Andrea T.; Dolcos, Florin

2014-01-01

The memory-enhancing effect of emotion has been linked to the engagement of emotion- and memory-related medial temporal lobe (MTL) regions (amygdala-AMY; hippocampus-HC; parahippocampus-PHC), during both encoding and retrieval. However, recognition tasks used to investigate the neural correlates of retrieval make it difficult to distinguish MTL engagement linked to retrieval success (RS) from that linked to incidental encoding success (ES) during retrieval. This issue has been investigated for retrieval of non-emotional memories, but not for emotional memory retrieval. To address this, we used event-related functional MRI in conjunction with an emotional distraction and two episodic memory tasks (one testing memory for distracter items and the other testing memory for new/lure items presented in the first memory task). This paradigm allowed for dissociation of MTL activity specifically linked to RS from that linked to both RS and incidental ES during retrieval. There were two novel findings regarding the neural correlates of emotional memory retrieval. First, greater emotional RS was identified bilaterally in AMY, HC, and PHC. However, AMY activity was most impacted when accounting for ES activity, as only RS activity in left AMY was dissociated from ES activity during retrieval, whereas portions of HC and PHC showing greater emotional RS were largely uninvolved in ES. Second, an earlier and more anteriorly spread response (left AMY and bilateral HC, PHC) was linked to greater emotional RS activity, whereas a later and more posteriorly localized response (right posterior PHC) was linked to greater neutral RS activity. These findings shed light on MTL mechanisms subserving the memory-enhancing effect of emotion at retrieval. PMID:24917798

Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) Gene and Metabolic Risk Factors in the EPIC-Potsdam Study

PubMed Central

Arregui, Maria; Buijsse, Brian; Stefan, Norbert; Corella, Dolores; Fisher, Eva; di Giuseppe, Romina; Coltell, Oscar; Knüppel, Sven; Aleksandrova, Krasimira; Joost, Hans-Georg; Boeing, Heiner; Weikert, Cornelia

2012-01-01

Background Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question. Methods In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A. Results No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction. Conclusion These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given the results from animal models, heterogeneity of human SCD1 warrants further investigation, in particular with regard to rare variants. PMID:23139775

Promiscuity and selectivity of bitter molecules and their receptors.

PubMed

Di Pizio, Antonella; Niv, Masha Y

2015-07-15

Bitter taste is essential for survival, as it protects against consuming poisonous compounds, which are often bitter. Bitter taste perception is mediated by bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs). The number of TAS2R subtypes is species-dependent, and varies from 3 in chicken to 50 in frog. TAS2Rs present an intriguing case for studying promiscuity: some of the receptors are still orphan, or have few known agonists, while others can be activated by numerous, structurally dissimilar compounds. The ligands also vary in the repertoire of TAS2Rs that they activate: some bitter compounds are selective toward a single TAS2R, while others activate multiple TAS2Rs. Selectivity/promiscuity profile of bitter taste receptors and their compounds was explored by a chemoinformatic approach. TAS2R-promiscuous and TAS2R-selective bitter molecules were found to differ in chemical features, such as AlogP, E-state, total charge, number of rings, globularity, and heavy atom count. This allowed the prediction of bitter ligand selectivity toward TAS2Rs. Interestingly, while promiscuous TAS2Rs are activated by both TAS2R-promiscuous and TAS2R-selective compounds, almost all selective TAS2Rs in human are activated by promiscuous compounds, which are recognized by other TAS2Rs anyway. Thus, unique ligands, that may have been the evolutionary driving force for development of selective TAS2Rs, still need to be unraveled. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential Delivery of Genomic Double-Stranded RNA Causes Reovirus Strain-Specific Differences in Interferon Regulatory Factor 3 Activation.

PubMed

Stuart, Johnasha D; Holm, Geoffrey H; Boehme, Karl W

2018-05-01

Serotype 3 (T3) reoviruses induce substantially more type 1 interferon (IFN-I) secretion than serotype 1 (T1) strains. However, the mechanisms underlying differences in IFN-I production between T1 and T3 reoviruses remain undefined. Here, we found that differences in IFN-I production between T1 and T3 reoviruses correlate with activation of interferon regulatory factor 3 (IRF3), a key transcription factor for the production of IFN-I. T3 strain rsT3D activated IRF3 more rapidly and to a greater extent than the T1 strain rsT1L, in simian virus 40 (SV40) immortalized endothelial cells (SVECs). Differences in IRF3 activation between rsT1L and rsT3D were observed in the first hours of infection and were independent of de novo viral RNA and protein synthesis. NF-κB activation mirrored IRF3 activation, with rsT3D inducing more NF-κB activity than rsT1L. We also found that IRF3 and NF-κB are activated in a mitochondrial antiviral-signaling protein (MAVS)-dependent manner. rsT1L does not suppress IRF3 activation, as IRF3 phosphorylation could be induced in rsT1L-infected cells. Transfected rsT1L and rsT3D RNA induced IRF3 phosphorylation, indicating that genomic RNA from both strains has the capacity to activate IRF3. Finally, bypassing the normal route of reovirus entry by transfecting in vitro -generated viral cores revealed that rsT1L and rsT3D core particles induced equivalent IRF3 activation. Taken together, our findings indicate that entry-related events that occur after outer capsid disassembly, but prior to deposition of viral cores into the cytoplasm, influence the efficiency of IFN-I responses to reovirus. This work provides further insight into mechanisms by which nonenveloped viruses activate innate immune responses. IMPORTANCE Detection of viral nucleic acids by the host cell triggers type 1 interferon (IFN-I) responses, which are critical for containing and clearing viral infections. Viral RNA is sensed in the cytoplasm by cellular receptors that initiate signaling pathways, leading to the activation of interferon regulatory factor 3 (IRF3) and NF-κB, key transcription factors required for IFN-I induction. Serotype 3 (T3) reoviruses induce significantly more IFN-I than serotype 1 (T1) strains. In this work, we found that differences in IFN-I production by T1 and T3 reoviruses correlate with differential IRF3 activation. Differences in IRF3 activation are not caused by a blockade of the IRF3 activation by a T1 strain. Rather, differences in events during the late stages of viral entry determine the capacity of reovirus to activate host IFN-I responses. Together, our work provides insight into mechanisms of IFN-I induction by nonenveloped viruses. Copyright © 2018 American Society for Microbiology.

Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers.

PubMed

Ding, Mingcui; Yang, Yongli; Duan, Xiaoran; Wang, Sihua; Feng, Xiaolei; Wang, Tuanwei; Wang, Pengpeng; Liu, Suxiang; Li, Lei; Liu, Junling; Tang, Lixia; Niu, Xinhua; Zhang, Yuhong; Li, Guoyu; Yao, Wu; Cui, Liuxin; Wang, Wei

2018-06-18

Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P < 0.001). Multivariate analysis indicates that exposure group (b = - 1.016, P < 0.001), agender (b = 0.365, P < 0.001), drinking (b = 0.271, P = 0.004) and TERF1rs3863242 (b = - 0.368, P = 0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate. Copyright © 2018 Elsevier Inc. All rights reserved.

VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System.

PubMed

Krute, Christina N; Rice, Kelly C; Bose, Jeffrey L

2017-03-01

In previous studies, we identified the fatty acid kinase virulence factor regulator B (VfrB) as a potent regulator of α-hemolysin and other virulence factors in Staphylococcus aureus In this study, we demonstrated that VfrB is a positive activator of the SaeRS two-component regulatory system. Analysis of vfrB , saeR , and saeS mutant strains revealed that VfrB functions in the same pathway as SaeRS. At the transcriptional level, the promoter activities of SaeRS class I ( coa ) and class II ( hla ) target genes were downregulated during the exponential growth phase in the vfrB mutant, compared to the wild-type strain. In addition, saePQRS expression was decreased in the vfrB mutant strain, demonstrating a need for this protein in the autoregulation of SaeRS. The requirement for VfrB-mediated activation was circumvented when SaeS was constitutively active due to an SaeS (L18P) substitution. Furthermore, activation of SaeS via human neutrophil peptide 1 (HNP-1) overcame the dependence on VfrB for transcription from class I Sae promoters. Consistent with the role of VfrB in fatty acid metabolism, hla expression was decreased in the vfrB mutant with the addition of exogenous myristic acid. Lastly, we determined that aspartic acid residues D38 and D40, which are predicted to be key to VfrB enzymatic activity, were required for VfrB-mediated α-hemolysin production. Collectively, this study implicates VfrB as a novel accessory protein needed for the activation of SaeRS in S. aureus IMPORTANCE The SaeRS two-component system is a key regulator of virulence determinant production in Staphylococcus aureus Although the regulon of this two-component system is well characterized, the activation mechanisms, including the specific signaling molecules, remain elusive. Elucidating the complex regulatory circuit of SaeRS regulation is important for understanding how the system contributes to disease causation by this pathogen. To this end, we have identified the fatty acid kinase VfrB as a positive regulatory modulator of SaeRS-mediated transcription of virulence factors in S. aureus In addition to describing a new regulatory aspect of SaeRS, this study establishes a link between fatty acid kinase activity and virulence factor regulation. Copyright © 2017 American Society for Microbiology.

Local and Global Resting State Activity in the Noradrenergic and Dopaminergic Pathway Modulated by Reboxetine and Amisulpride in Healthy Subjects

PubMed Central

Wiegers, Maike; Walter, Martin; Abler, Birgit; Graf, Heiko

2016-01-01

Background: Various psychiatric populations are currently investigated with resting state fMRI, with the aim of individualizing diagnostics and treatment options and improving treatment outcomes. Many of these studies are conducted in large naturalistic samples, providing rich insights regarding disease-related neural alterations, but with the common psychopharmacological medication limiting interpretations of the results. We therefore investigated the effects of common noradrenergic and anti-dopaminergic medications on local and global resting state activity (rs-activity) in healthy volunteers to further the understanding of the respective effects independent from disease-related alterations. Methods: Within a randomized, double-blind, placebo-controlled crossover design, we investigated 19 healthy male subjects by resting state fMRI after the intake of reboxetine (4mg/d), amisulpride (200mg/d), and placebo for 7 days each. Treatment-related differences in local and global rs-activity were measured by the fractional amplitude of low frequency fluctuations (fALFF) and resting state functional connectivity (rs-FC). Results: fALFF revealed alterations of local rs-activity within regions of the core noradrenergic pathway, including the locus coeruleus under reboxetine, correlated with its plasma levels. Moreover, reboxetine led to increased rs-FC between regions within this pathway, i.e. the locus coeruleus, tectum, thalamus, and amygdala. Amisulpride modulated local rs-activity of regions within the dopaminergic pathway, with the altered signal in the putamen correlating with amisulpride plasma levels. Correspondingly, amisulpride increased rs-FC between regions of the dopaminergic pathway comprising the substantia nigra and putamen. Conclusion: Our data provide evidence of how psychopharmacological agents alter local and global rs-activity within the respective neuroanatomical pathways in healthy subjects, which may help with interpreting data in psychiatric populations. PMID:26209860

AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa

PubMed Central

Lau, Calvin Ho-Fung; Krahn, Thomas; Gilmour, Christie; Mullen, Erin; Poole, Keith

2015-01-01

AmgRS is an envelope stress-responsive two-component system and aminoglycoside resistance determinant in Pseudomonas aeruginosa that is proposed to protect cells from membrane damage caused by aminoglycoside-generated mistranslated polypeptides. Consistent with this, a ΔamgR strain showed increased aminoglycoside-promoted membrane damage, damage that was largely absent in AmgRS-activated amgS-mutant strains. Intriguingly, one such mutation, V121G, while providing for enhanced resistance to aminoglycosides, rendered P. aeruginosa susceptible to several ribosome-targeting nonaminoglycoside antimicrobials that are inducers and presumed substrates of the MexXY-OprM multidrug efflux system. Surprisingly, the amgSV121G mutation increased mexXY expression threefold, suggesting that export of these nonaminoglycosides was compromised in the amgSV121G mutant. Nonetheless, a link was established between AmgRS activation and mexXY expression and this was confirmed in studies showing that aminoglycoside-promoted mexXY expression is dependent on AmgRS. While nonaminoglycosides also induced mexXY expression, this was not AmgRS-dependent, consistent with these agents not generating mistranslated polypeptides and not activating AmgRS. The aminoglycoside inducibility of mexXY was abrogated in a mutant lacking the AmgRS target genes htpX and PA5528, encoding a presumed cytoplasmic membrane-associated protease and a membrane protein of unknown function, respectively. Thus, aminoglycoside induction of mexXY is a response to membrane damage and activation of the AmgRS two-component system. PMID:25450797

Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex.

PubMed

Zhang, Haopeng; Cilz, Nicholas I; Yang, Chuanxiu; Hu, Binqi; Dong, Hailong; Lei, Saobo

2015-11-01

Whereas the ionotropic glutamate receptors are the major mediator in glutamatergic transmission, the metabotropic glutamate receptors (mGluRs) usually play a modulatory role. Whereas the entorhinal cortex (EC) is an essential structure involved in the generation and propagation of epilepsy, the roles and mechanisms of mGluRs in epilepsy in the EC have not been determined. Here, we studied the effects of activation of group II metabotropic glutamate receptors (mGluRs II) on epileptiform activity induced by picrotoxin or deprivation of extracellular Mg2+ and neuronal excitability in the medial EC. We found that activation of mGluRs II by application of the selective agonist, LY354740, exerted robust inhibition on epileptiform activity. LY354740 hyperpolarized entorhinal neurons via activation of a K+ conductance and inhibition of a Na+ -permeable channel. LY354740-induced hyperpolarization was G protein-dependent, but independent of adenylyl cyclase and protein kinase A. However, the function of Gβγ was involved in mGluRs II-mediated depression of both neuronal excitability and epileptiform activity. Our results provide a novel cellular mechanism to explain the antiepileptic effects of mGluRs II in the treatment of epilepsy. © 2015 Wiley Periodicals, Inc.

Role of alloy additions on strengthening in 17-4 PH stainless steel

NASA Astrophysics Data System (ADS)

Murthy, Arpana Sudershan

Alloy modifications by addition of niobium (Nb), vanadium (V), nitrogen (N) and cobalt (Co) to cast 17-4 PH steel were investigated to determine the effect on mechanical properties. Additions of Nb, V, and N increased the yield strength from 1120 MPa to 1310 MPa while decreased the room temperature charpy V notch (CVN) toughness from 20 J to four Joules. The addition of Co to cast 17-4 PH steel enhanced the yield strength and CVN toughness from 1140 MPa to 1290 MPa and from 3.7 J to 5.5 J, respectively. In the base 17-4 PH steel, an increase in block width from 2.27 ± 0.10 μm in the solution treated condition to 3.06 ± 0.17 μm upon aging at 755 K was measured using orientation image microscopy. Cobalt inhibited recrystallization and block boundary migration during aging resulting in a finer martensitic block structure. The influence of Co on copper (Cu) precipitation in steels was studied using atom probe tomography. A narrower precipitate size distribution was observed in the steels with Co addition. The concentration profile across the matrix / precipitate interface indicated rejection of Co atoms from the copper precipitates. This behavior was observed to be energetically favorable using first principle calculations. The activation energies for Cu precipitation increased from 205 kJ/ mol in the non-cobalt containing alloy, to 243 kJ/ mol, and 272 kJ/ mol in alloys with 3 wt. %Co, and 7 wt. % Co, respectively. The role of Co on Cu precipitation in cast 17-4 PH steel is proposed as follows: (i) Co is rejected out of the Cu precipitate and sets up a barrier to the growth of the Cu precipitate; (ii) results in Cu precipitates of smaller size and narrower distribution; (iii) the coarsening of Cu precipitates is inhibited; and (iv) the activation energy for Cu precipitation increases.

Prolactin Signaling through the Short Form of Its Receptor Represses Forkhead Transcription Factor FOXO3 and Its Target Gene Galt Causing a Severe Ovarian Defect

PubMed Central

Halperin, Julia; Devi, Sangeeta Y.; Elizur, Shai; Stocco, Carlos; Shehu, Aurora; Rebourcet, Diane; Unterman, Terry G.; Leslie, Nancy D.; Le, Jamie; Binart, Nadine; Gibori, Geula

2008-01-01

Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation. PMID:17975019

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

PubMed

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

2017-08-01

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

Loss of retinoschisin (RS1) cell surface protein in maturing mouse rod photoreceptors elevates the luminance threshold for light-driven translocation of transducin but not arrestin.

PubMed

Ziccardi, Lucia; Vijayasarathy, Camasamudram; Bush, Ronald A; Sieving, Paul A

2012-09-19

Loss of retinoschisin (RS1) in Rs1 knock-out (Rs1-KO) retina produces a post-photoreceptor phenotype similar to X-linked retinoschisis in young males. However, Rs1 is expressed strongly in photoreceptors, and Rs1-KO mice have early reduction in the electroretinogram a-wave. We examined light-activated transducin and arrestin translocation in young Rs1-KO mice as a marker for functional abnormalities in maturing rod photoreceptors. We found a progressive reduction in luminance threshold for transducin translocation in wild-type (WT) retinas between postnatal days P18 and P60. At P21, the threshold in Rs1-KO retinas was 10-fold higher than WT, but it decreased to <2.5-fold higher by P60. Light-activated arrestin translocation and re-translocation of transducin in the dark were not affected. Rs1-KO rod outer segment (ROS) length was significantly shorter than WT at P21 but was comparable with WT at P60. These findings suggested a delay in the structural and functional maturation of Rs1-KO ROS. Consistent with this, transcription factors CRX and NRL, which are fundamental to maturation of rod protein expression, were reduced in ROS of Rs1-KO mice at P21 but not at P60. Expression of transducin was 15-30% lower in P21 Rs1-KO ROS and transducin GTPase hydrolysis was nearly twofold faster, reflecting a 1.7- to 2.5-fold increase in RGS9 (regulator of G-protein signaling) level. Transduction protein expression and activity levels were similar to WT at P60. Transducin translocation threshold elevation indicates photoreceptor functional abnormalities in young Rs1-KO mice. Rapid reduction in threshold coupled with age-related changes in transduction protein levels and transcription factor expression are consistent with delayed maturation of Rs1-KO photoreceptors.

Photometry of symbiotic stars. XI. EG And, Z And, BF Cyg, CH Cyg, CI Cyg, V1329 Cyg, TX CVn, AG Dra, RW Hya, AR Pav, AG Peg, AX Per, QW Sge, IV Vir and the LMXB V934 Her

NASA Astrophysics Data System (ADS)

Skopal, A.; Pribulla, T.; Vaňko, M.; Velič, Z.; Semkov, E.; Wolf, M.; Jones, A.

2004-02-01

We present new photometric observations of EG And, Z And, BF Cyg, CH Cyg, CI Cyg, V1329 Cyg, TX CVn, AG Dra, RW Hya, AG Peg, AX Per, IV Vir and the peculiar M giant V934 Her, which were made in the standard Johnson UBV(R) system. QW Sge was measured in the Kron-Cousin B, V, RC, IC system and for AR Pav we present its new visual estimates. The current issue gathers observations of these objects to December 2003. The main results can be summarized as follows: EG And: The primary minimum in the U light curve (LC) occurred at the end of 2002. A 0.2 -- 0.3 mag brightening in U was detected in the autumn of 2003. Z And: At around August 2002 we detected for the first time a minimum, which is due to eclipse of the active object by the red giant. Measurements from 2003.3 are close to those of a quiescent phase. BF Cyg: In February 2003 a short-term flare developed in the LC. A difference in the depth of recent minima was detected. CH Cyg: This star was in a quiescent phase at a rather bright state. A shallow minimum occurred at ˜ JD 2 452 730, close to the position of the inferior conjunction of the giant in the inner binary of the triple-star model of CH Cyg. CI Cyg: Our observations cover the descending branch of a broad minimum. TX CVn: At/around the beginning of 2003 the star entered a bright stage containing a minimum at ˜ JD 2 452 660. AG Dra: New observations revealed two eruptions, which peaked in October 2002 and 2003 at ˜ 9.3 in U. AR Pav: Our new visual estimates showed a transient disappearance of a wave-like modulation in the star's brightness between the minima at epochs E = 66 and E = 68 and its reappearance. AG Peg: Our measurements from the end of 2001 showed rather complex profile of the LC. RW Hya: Observations follow behaviour of the wave-like variability of quiet symbiotics. AX Per: In May 2003 a 0.5 mag flare was detected following a rapid decrease of the light to a minimum. QW Sge: CCD observations in B, V, RC, IC bands cover a period from 1994.5 to 2003.5. An increase in the star's brightness by about 1 mag was observed in all passbands in 1997. Less pronounced brightening was detected in 1999/2000. V934 Her: Our observations did not show any larger variation in the optical as a reaction to its X-ray activity.

Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

PubMed

Laugwitz, K L; Weig, H J; Moretti, A; Hoffmann, E; Ueblacker, P; Pragst, I; Rosport, K; Schömig, A; Ungerer, M

2001-04-13

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or beta(2)-ARS:

NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase

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

Kohda, D.; Kawai, G.; Yokoyama, S.

1987-10-06

The 400-MHz /sup 1/H NMR spectra of L-isoleucine and L-valine were measured in the presence of Escherichia coli isoleucyl-tRNA synthetase (IleRS). Because of chemical exchange of L-isoleucine or L-valine between the free state and the IleRS-bound state, a transferred nuclear Overhauser effect (TRNOE) was observed among proton resonances of L-isoleucine or L-valine. However, in the presence of isoleucyl adenylate tightly bound to the amino acid activation site of IleRS, no TRNOE for L-isoleucine or L-valine was observed. This indicates that the observed TRNOE is due to the interaction of L-isoleucine or L-valine with the amino acid activation site of IleRS.more » The conformations of these amino acids in the amino acid activation site of IleRS were determined by the analyses of time dependences of TRNOEs and TRNOE action spectra. The IleRS-bound L-isoleucine takes the gauche/sup +/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond and the trans form about the C/sub ..beta../-C/sub ..gamma../sub 1// bond. The IleRS-bound L-valine takes the guache/sup -/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond. Thus, the conformation of the IleRS-bound L-valine is the same as that of IleRS-bound L-isoleucine except for the delta-methyl group. The side chain of L-isoleucine or L-valine lies in an aliphatic hydrophobic pocket of the active site of IleRS. Such hydrophobic interaction with IleRS is more significant for L-isoleucine than for L-valine. The TRNOE analysis is useful for studying the amino acid discrimination mechanism of aminoacyl-tRNA synthetases.« less

Aerobic capacity over 16 years in patients with rheumatoid arthritis: Relationship to disease activity and risk factors for cardiovascular disease

PubMed Central

Sundström, Björn; Innala, Lena; Rantapää-Dahlqvist, Solbritt; Wållberg-Jonsson, Solveig

2017-01-01

The aim of this study was to analyse the change in aerobic capacity from disease onset of rheumatoid arthritis (RA) over 16.2 years, and its associations with disease activity and cardiovascular risk factors. Twenty-five patients (20 f/5 m), diagnosed with RA 1995-2002 were tested at disease onset and after mean 16.2 years. Parameters measured were: sub-maximal ergometer test for aerobic capacity, functional ability, self-efficacy, ESR, CRP and DAS28. At follow-up, cardiovascular risk factors were assessed as blood lipids, glucose concentrations, waist circumference, body mass index (BMI), body composition, pulse wave analysis and carotid intima-media thickness. Aerobic capacity [median (IQR)] was 32.3 (27.9-42.1) ml O2/kg x min at disease onset, and 33.2 (28.4-38.9) at follow-up (p>0.05). Baseline aerobic capacity was associated with follow-up values of: BMI (rs = -.401, p = .047), waist circumference (rs = -.498, p = .011), peripheral pulse pressure (rs = -.415, p = .039) self-efficacy (rs = .420, p = .037) and aerobic capacity (rs = .557, p = .004). In multiple regression models adjusted for baseline aerobic capacity, disease activity at baseline and over time predicted aerobic capacity at follow-up (AUC DAS28, 0-24 months; β = -.14, p = .004). At follow-up, aerobic capacity was inversely associated with blood glucose levels (rs = -.508, p = .016), BMI (rs = -.434, p = .030), body fat% (rs = -.419, p = .037), aortic pulse pressure (rs = -.405, p = .044), resting heart rate (rs = -.424, p = .034) and self-efficacy (rs = .464, p = .020) at follow-up. We conclude that the aerobic capacity was maintained over 16 years. High baseline aerobic capacity associated with favourable measures of cardiovascular risk factors at follow-up. Higher disease activity in early stages of RA predicted lower aerobic capacity after 16.2 years. PMID:29272303

Aerobic capacity over 16 years in patients with rheumatoid arthritis: Relationship to disease activity and risk factors for cardiovascular disease.

PubMed

Hörnberg, Kristina; Sundström, Björn; Innala, Lena; Rantapää-Dahlqvist, Solbritt; Wållberg-Jonsson, Solveig

2017-01-01

The aim of this study was to analyse the change in aerobic capacity from disease onset of rheumatoid arthritis (RA) over 16.2 years, and its associations with disease activity and cardiovascular risk factors. Twenty-five patients (20 f/5 m), diagnosed with RA 1995-2002 were tested at disease onset and after mean 16.2 years. Parameters measured were: sub-maximal ergometer test for aerobic capacity, functional ability, self-efficacy, ESR, CRP and DAS28. At follow-up, cardiovascular risk factors were assessed as blood lipids, glucose concentrations, waist circumference, body mass index (BMI), body composition, pulse wave analysis and carotid intima-media thickness. Aerobic capacity [median (IQR)] was 32.3 (27.9-42.1) ml O2/kg x min at disease onset, and 33.2 (28.4-38.9) at follow-up (p>0.05). Baseline aerobic capacity was associated with follow-up values of: BMI (rs = -.401, p = .047), waist circumference (rs = -.498, p = .011), peripheral pulse pressure (rs = -.415, p = .039) self-efficacy (rs = .420, p = .037) and aerobic capacity (rs = .557, p = .004). In multiple regression models adjusted for baseline aerobic capacity, disease activity at baseline and over time predicted aerobic capacity at follow-up (AUC DAS28, 0-24 months; β = -.14, p = .004). At follow-up, aerobic capacity was inversely associated with blood glucose levels (rs = -.508, p = .016), BMI (rs = -.434, p = .030), body fat% (rs = -.419, p = .037), aortic pulse pressure (rs = -.405, p = .044), resting heart rate (rs = -.424, p = .034) and self-efficacy (rs = .464, p = .020) at follow-up. We conclude that the aerobic capacity was maintained over 16 years. High baseline aerobic capacity associated with favourable measures of cardiovascular risk factors at follow-up. Higher disease activity in early stages of RA predicted lower aerobic capacity after 16.2 years.

A Radish Basic Helix-Loop-Helix Transcription Factor, RsTT8 Acts a Positive Regulator for Anthocyanin Biosynthesis

PubMed Central

Lim, Sun-Hyung; Kim, Da-Hye; Kim, Jae K.; Lee, Jong-Yeol; Ha, Sun-Hwa

2017-01-01

The MYB-bHLH-WDR (MBW) complex activates anthocyanin biosynthesis through the transcriptional regulation. RsMYB1 has been identified as a key player in anthocyanin biosynthesis in red radish (Raphanus sativus L.), but its partner bHLH transcription factor (TF) remains to be determined. In this study, we isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus designated this gene RsTT8. Subcellular localization analysis showed that RsTT8-sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8 expression levels in three radish varieties (N, C, and D) that display different red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C variety and the leaves and skins of the D variety exhibit intense red pigmentation; in these tissues, RsTT8 expression showed totally positive association with the expression of RsMYB1 TF and of five of eight tested anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS). Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves dramatically increased the expression of endogenous anthocyanin biosynthesis genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR), and a transient transactivation assay indicated that RsTT8 activates the RsCHS and RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8 restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively. Together, these results show that RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin biosynthesis. PMID:29167678

Application of back propagation artificial neural network on genetic variants in adiponectin ADIPOQ, peroxisome proliferator-activated receptor-γ, and retinoid X receptor-α genes and type 2 diabetes risk in a Chinese Han population.

PubMed

Shi, Hui; Lu, Ying; Du, Juan; Du, Wencong; Ye, Xinhua; Yu, Xiaofang; Ma, Jianhua; Cheng, Jinluo; Gao, Yanqin; Cao, Yuanyuan; Zhou, Ling; Li, Qian

2012-03-01

Our study was designed to explore the applied characteristics of the back propagation artificial neural network (BPANN) on studying the genetic variants in adipnectin ADIPOQ, peroxisome proliferator-activated receptor (PPAR)-γ, and retinoid X receptor-α (RXR-α) genes and type 2 diabetes mellitus (T2DM) risks in a Chinese Han population. We used BPANN as the fitting model based on data gathered from T2DM patients (n=913) and normal controls (n=1,001). The mean impact value (MIV) for each input variables were calculated, and the sequence of the factors according to their absolute MIVs was sorted. The results from BPANN were compared with multiple logistic regression analysis, and the generalized multifactor dimensionality reduction (GMDR) method was used to calculate the joint effects of ADIPOQ, PPAR-γ, and RXR-α genes. By BPANN analysis, the sequence according to the importance of the T2DM risk factors was in the order of serum adiponectin level, rs3856806, rs7649121, hypertension, rs3821799, rs17827276, rs12495941, rs4240711, age, rs16861194, waist circumference, rs2241767, rs2920502, rs1063539, alcohol drinking, smoking, hyperlipoproteinemia, gender, rs3132291, T2DM family history, rs4842194, rs822394, rs1801282, rs1045570, rs16861205, rs6537944, body mass index, rs266729, and rs1801282. However, compared with multiple logistic regression analysis, only 11 factors were statistically significant. After overweight and obesity were taken as environment adjustment factors into the analysis, model A2 B4 C5 C6 C8 (rs3856806, rs4240711, rs7649121, rs3821799, rs12495941) was the best model (coefficient of variation consistency=10/10, P=0.0107) in the GMDR method. These results suggested the interactions of ADIPOQ, PPAR-γ, and RXR-α genes might play a role in susceptibility to T2DM. BPANN could be used to analyze the risk factors of diseases and provide more complicated relationships between inputs and outputs.

NVR Home Page

Science.gov Websites

Internet Explorer. Please use the latest version of Internet Explorer for full functionality. CVN 69 NVR Online The NVR is a product of the NAVSEA Shipbuilding Support Office (NAVSHIPSO) In cooperation with Group (NAVSEA 05C) Images Courtesy of US Navy Photos and the US Navy Fact File Naval Sea Systems Command

Swift observations of SDSS J141118.31+481257.6 during superoutburst

NASA Astrophysics Data System (ADS)

Rivera Sandoval, L. E.; Maccarone, T.

2018-06-01

We report on follow-up Swift observations of the AM CVn-type binary SDSS J141118.31+481257.6 (ATEL #11668, #11672). Based on ground based photometry, the re-brightening previous to the current superoutburst was reported on 2018-June-1 (https://www.aavso.org/aavso-alert-notice-636).

Hiding in Plain Sight: The Low Mass Helium Star Companion of EL CVn

NASA Astrophysics Data System (ADS)

Gies, Douglas

2016-10-01

Binary stars with orbital periods of a decade or less are destined to interact during their evolution. The mass donor star among intermediate binaries may be stripped of its envelope by mass transfer to reveal its helium core. In cases that avoid merger, the low mass helium star will remain in a binary orbit but be lost in the glare of the mass gainer star.Thanks to photometric time series from Kepler and WASP, we now know of 27 such systems that are oriented to produce mutual eclipses. Althoughthe helium star companions are too small and faint in the optical bandfor spectroscopic detection, they contribute a larger fraction of the total flux in the ultraviolet. HST/COS measurements of one long period system, KOI-81, successfully detected the helium star's spectrum in the far-ultraviolet, leading to estimates of its mass and temperature. Here we propose to obtain new HST/COS FUV spectra of the prototype of this class of evolved binaries, EL CVn, and to determine the mass and physical properties of a star that barely escaped a merger.

The effect of resistant starch (RS) on the bovine rumen microflora and isolation of RS-degrading bacteria.

PubMed

Jung, Dong-Hyun; Seo, Dong-Ho; Kim, Ga-Young; Nam, Young-Do; Song, Eun-Ji; Yoon, Shawn; Park, Cheon-Seok

2018-06-01

Resistant starch (RS) in the diet reaches the large intestine without degradation, where it is decomposed by the commensal microbiota. The fermentation of RS produces secondary metabolites including short-chain fatty acids (SCFAs), which have been linked to a variety of physiological and health effects. Therefore, the availability of RS as a prebiotic is a current issue. The objectives of this study were (1) to use metagenomics to observe microbial flora changes in Bos taurus coreanae rumen fluid in the presence of RS and (2) to isolate RS-degrading microorganisms. The major microbial genus in a general rumen fluid was Succiniclasticum sp., whereas Streptococcus sp. immediately predominated after the addition of RS into the culture medium and was then drastically replaced by Lactobacillus sp. The presence of Bifidobacterium sp. was also observed continuously. Several microorganisms with high RS granule-degrading activity were identified and isolated, including B. choerinum FMB-1 and B. pseudolongum FMB-2. B. choerinum FMB-1 showed the highest RS-hydrolyzing activity and degraded almost 60% of all substrates tested. Coculture experiments demonstrated that Lactobacillus brevis ATCC 14869, which was isolated from human feces, could grow using reducing sugars generated from RS by B. choerinum FMB-1. These results suggest that Bifidobacterium spp., especially B. choerinum FMB-1, are the putative primary degrader of RS in rumen microbial flora and could be further studied as probiotic candidates.

Further Charpy impact test results of low activation ferritic alloys, irradiated at 430{degrees}C to 67 dpa

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

Schubert, L.E.; Hamilton, M.L.; Gelles, D.S.

1997-04-01

Miniature CVN specimens of four ferritic alloys, GA3X, F82H, GA4X and HT9, have been impact tested following irradiation at 430{degrees}C to 67 dpa. Comparison of the results with those of the previously tested lower dose irradiation condition indicates that the GA3X and F82H alloys, two primary candidate low activation alloys, exhibit virtually identical behavior following irradiation at 430{degrees}C to {approximately}67 dpa and at 370{degrees}C to {approximately}15 dpa. Very little shift is observed in either DBTT or USE relative to the unirradiated condition. The shifts in DBTT and USE observed in both GA4X and HT9 were smaller after irradiation at 430{degrees}Cmore » to {approximately}67 dpa than after irradiation at 370{degrees}C to {approximately}15 dpa.« less

Chemical characterization and anti-inflammatory effect of rauvolfian, a pectic polysaccharide of Rauvolfia callus.

PubMed

Popov, S V; Vinter, V G; Patova, O A; Markov, P A; Nikitina, I R; Ovodova, R G; Popova, G Yu; Shashkov, A S; Ovodov, Yu S

2007-07-01

The pectic polysaccharide named rauvolfian RS was obtained from the dried callus of Rauvolfia serpentina L. by extraction with 0.7% aqueous ammonium oxalate. Crude rauvolfian RS was purified using membrane ultrafiltration to yield the purified rauvolfian RSP in addition to glucan as admixture from the callus, with molecular weights 300 and 100-300 kD, respectively. A peroral pretreatment of mice with the crude and purified samples of rauvolfian (RS and RSP) was found to decrease colonic macroscopic scores, the total area of damage, and tissue myeloperoxidase activity in colons as compared with a colitis group. RS and RSP were shown to stimulate production of mucus by colons of the colitis mice. RSP appeared to be an active constituent of the parent RS. The glucan failed to possess anti-inflammatory activity.

Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms.

PubMed

Park, Hae Jeong; Lee, Soojung; Ju, Eunji; Jones, Jayre A; Choi, Inyeong

2017-03-01

Genome-wide association studies have identified the single nucleotide polymorphism (SNP) rs3278 in the human SLC4A7 gene as one of the marker loci for addiction vulnerability. This marker is located in an intron of the gene, and its genomic role has been unknown. In this study, we examined rs3278 and three adjacent SNPs prevalent in alcoholics for their effects on an alternative promoter that would lead to the production of the NH 2 -terminally truncated protein NBCn1ΔN450, missing the first 450 amino acids. Analysis of the transcription start site database and a promoter prediction algorithm identified a cluster of three promoters in intron 7 and two short CpG-rich sites in intron 6. The promoter closest to rs3278 showed strong transcription activity in luciferase reporter gene assays. Major-to-minor allele substitution at rs3278 resulted in increased transcription activity. Equivalent substitutions at adjacent rs3772723 (intron 7) and rs13077400 (exon 8) had negligible effect; however, the substitution at nonsynonymous rs3755652 (exon 8) increased the activity by more than twofold. The concomitant substitution at rs3278/rs3755652 produced an additive effect. The rs3755652 had more profound effects on the promoter than the upstream regulatory CpG sites. The amino acid change E326K caused by rs3755652 had negligible effect on transporter function. In HEK 293 cells, NBCn1ΔN450 was expressed in plasma membranes, but at significantly lower levels than the nontruncated NBCn1-E. The pH change mediated by NBCn1ΔN450 was also low. We conclude that rs3278 and rs3755652 stimulate an alternative transcription of the SLC4A7 gene, increasing the production of a defective transporter. Copyright © 2017 the American Physiological Society.

Muscarinic Receptors Modulate Dendrodendritic Inhibitory Synapses to Sculpt Glomerular Output

PubMed Central

Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus

2015-01-01

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. PMID:25855181

Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

PubMed

Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

2015-04-08

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

Hypoxia/oxidative stress alters the pharmacokinetics of CPU86017-RS through mitochondrial dysfunction and NADPH oxidase activation.

PubMed

Gao, Jie; Ding, Xuan-sheng; Zhang, Yu-mao; Dai, De-zai; Liu, Mei; Zhang, Can; Dai, Yin

2013-12-01

Hypoxia/oxidative stress can alter the pharmacokinetics (PK) of CPU86017-RS, a novel antiarrhythmic agent. The aim of this study was to investigate the mechanisms underlying the alteration of PK of CPU86017-RS by hypoxia/oxidative stress. Male SD rats exposed to normal or intermittent hypoxia (10% O2) were administered CPU86017-RS (20, 40 or 80 mg/kg, ig) for 8 consecutive days. The PK parameters of CPU86017-RS were examined on d 8. In a separate set of experiments, female SD rats were injected with isoproterenol (ISO) for 5 consecutive days to induce a stress-related status, then CPU86017-RS (80 mg/kg, ig) was administered, and the tissue distributions were examined. The levels of Mn-SOD (manganese containing superoxide dismutase), endoplasmic reticulum (ER) stress sensor proteins (ATF-6, activating transcription factor 6 and PERK, PRK-like ER kinase) and activation of NADPH oxidase (NOX) were detected with Western blotting. Rat liver microsomes were incubated under N2 for in vitro study. The Cmax, t1/2, MRT (mean residence time) and AUC (area under the curve) of CPU86017-RS were significantly increased in the hypoxic rats receiving the 3 different doses of CPU86017-RS. The hypoxia-induced alteration of PK was associated with significantly reduced Mn-SOD level, and increased ATF-6, PERK and NOX levels. In ISO-treated rats, the distributions of CPU86017-RS in plasma, heart, kidney, and liver were markedly increased, and NOX levels in heart, kidney, and liver were significantly upregulated. Co-administration of the NOX blocker apocynin eliminated the abnormalities in the PK and tissue distributions of CPU86017-RS induced by hypoxia/oxidative stress. The metabolism of CPU86017-RS in the N2-treated liver microsomes was significantly reduced, addition of N-acetylcysteine (NAC), but not vitamin C, effectively reversed this change. The altered PK and metabolism of CPU86017-RS induced by hypoxia/oxidative stress are produced by mitochondrial abnormalities, NOX activation and ER stress; these abnormalities are significantly alleviated by apocynin or NAC.

Exploring PCK ability of prospective science teachers in reflective learning on heat and transfer

NASA Astrophysics Data System (ADS)

Nurmatin, S.; Rustaman, N. Y.

2016-02-01

Learning can be planned by the person him/herself when he or she tries to reflect his/her learning. A study involving prospective science teachers in junior secondary schools was carried out to analyze their ability on Pedagogical Content Knowledge (PCK) in reflective learning after teaching practice. The study was focused especially in creating Pedagogical and Professional Repertoires (PaP-eRs) as part of resource-folios. PaP-eRs as a narrative writing in the learning activities are created by prospective science teachers after lesson plan implementation. Making the narrative writing is intended that prospective science teachers can reflect their learning in teaching. Research subjects are six prospective science teachers who are implementing "Program Pengalaman Lapangan" (PPL) in two junior secondary schools in Bandung, West Java, Indonesia. All of them were assigned by supervisor teachers to teach VII grade students on certain topic "heat and its transfer". Instruments used as a means of collecting data in this study is PaP-eRs. Collected PaP-eRs were then analyzed using PaP-eRs analysis format as instruments for analysis. The result of analyzing PaP-eRs indicates that learning activities, which narrated, involve initial activities, core activities and final activities. However, any activity, which is narrated just superficial as its big line so the narration cannot be, used as reflective learning. It indicates that PCK ability of prospective science teachers in creating narrative writing (PaP-eRs) for reflective learning is still low.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis

PubMed Central

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof

2017-01-01

Introduction Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. Material and methods We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. Results There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04–2.28; p = 0.035). Conclusions The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity. PMID:28883856

Optical studies of X-ray peculiar chromosphereically active stars

NASA Astrophysics Data System (ADS)

Pandey, J. C.

2006-02-01

A multiwavelength study of the late-type active stars, selected on the basis of their X-ray and radio luminosities is presented in this thesis. For FR Cnc, a photometric period 0.8267 +/- 0.0004 d has been established. The strong variation in the phase and amplitude of the FR Cnc light curves when folded on this period implies the presence of evolving and migrating spots or spot groups on its surface. A photometric period of 18.802 +/- 0.074 has been discovered in the star HD 81032. The shape and amplitude of the photometric light curves of FR Cnc, HD 81032, HD 95559 and LO Peg are observed to be changing from one epoch to another. The change in the amplitude is mainly due to a change in the minimum of the light curve, and this May be due to a change in the spot coverage. This indicates that photometric variability is due to the presence of dark spots on the surface of active star. Two groups of spots are identified for FR Cnc and LO Peg. The spots are found to migrate, and migration periods of 0.97 year and 0.93 year are determined from the 4 years of data. A migration period of 1.12 years for one group of spots in LO Peg is also determined. Formation of a new group of spots in the star HD 95559 was also seen during our observations. A single large group of spots is found to migrate, and a migration period of 7.32 +/- 0.04 years is determined for HD 81032. The stars FR Cnc, HD 81032, HD 160934 and LO Peg are seen to be redder at the light minimum and we interpret this is due to the relatively cooler temperature of the darker regions present in the visible hemisphere. We find the lack of color-brightness correlation in the star HD 95559 and this May be due to the presence of bright faculae and plages like regions accompanied by dark spots in any one component of the this binary system. The optical spectroscopy of FR Cnc and HD 81032 carried out during 2002-2003, reveals the presence of strong and variable Ca II H and K, Halpha and Hbeta emission features indicative 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, for HD 81032 these properties suggest that it being an evolved RS! CVn binary of the long-period type Correlations between various physical quantities (Lx, Lrad, P and B-V) of active stars have been re-examined using a sample containing 248 active stars (101 dwarfs, 65 subgiants and 82 giants). It is a largest sample investigated so far. We did not find any appreciable changes in the correlations reported in previous studies. In addition to above, an Imaging Polarimeter has been fabricated for use with liquid-N2 cooled CCD camera and is designed to suit 104-cm Sampurnanand telescope with an f/13 focus at ARIES, Naini Tal. The instrument measures the linear polarization in broad B, V and R band, and has a field of view 2' x 2'.

Genetic and environmental risks for high blood pressure among African American mothers and daughters.

PubMed

Taylor, Jacquelyn Y; Maddox, Rosanna; Wu, Chun Yi

2009-07-01

To determine the relationship between genetic and environmental lifestyle factors (physical activity and sodium) on blood pressure (BP) among African-American women. In this cross-sectional study involving 108 African-American mothers and daughters from a Midwestern area, investigators obtained BP measurements, information on minutes of physical activity, amount of sodium intake, and buccal swab saliva samples. Of the 4 single nucleotide polymorphisms (SNPs) on the sodium bicarbonate cotransporter gene (SLC4A5), rs8179526 had a statistically significant interaction with cytosine/thymine (C/T) genotype by sodium status on systolic BP (SBP; p=.0077). For gene x physical activity interaction, 2 significant interactions (cytosine/adenine [C/A] genotype by physical activity and adenine/adenine [A/A] genotype by physical activity, p=.0107 and p=.0171, respectively) on SBP and 1 on diastolic BP (DBP; A/A genotype by physical activity, p=.0233) were found on rs1017783. Two significant guanine/adenine [G/A] genotype by physical activity interactions were found on rs6731545 for SBP and DBP (p=.0160 and p=.0492, respectively). A gene x environmental interaction with rs8179526 has a protective effect on SBP in African-American women with high sodium intake. Participants with C/T genotype of rs8179526 who consumed greater than 2,300 mg of sodium had lower SBP than those who consumed less than recommended. Women with thymine/thymine (T/T) genotype of rs8179526 who consumed greater than 2,300 mg had lower SBP than those who consumed less. Awareness of both the protective and deleterious properties of rs8179526 in African-American women may one day assist in determining appropriate treatment plans.

SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy.

PubMed

Shiota, Masaki; Fujimoto, Naohiro; Yokomizo, Akira; Takeuchi, Ario; Itsumi, Momoe; Inokuchi, Junichi; Tatsugami, Katsunori; Uchiumi, Takeshi; Naito, Seiji

2015-09-01

De novo androgen synthesis is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). During androgen synthesis, 5α-reductase encoded by SRD5A catalyses testosterone into more active dihydrotestosterone and may be involved in the progression to CRPC. Then, this study aimed to reveal the association between genetic variations in SRD5A and the prognosis in metastatic prostate cancer. We studied the polymorphisms rs518673 and rs166050 in SRD5A1, and rs12470143, rs523349, rs676033 and rs2208532 in SRD5A2 as well as the time to CRPC progression and overall survival in 104 patients with metastatic prostate cancer that had undergone primary ADT. The association between the polymorphisms and the progression to CRPC as well as overall survival was examined. Patients carrying the more active GG genotype in SRD5A2 rs523349 exhibited a higher risk of the progression (hazard ration [95% confidence interval], 1.93 [1.14-3.14], p=0.016) and death (hazard ration [95% confidence interval], 2.14 [1.16-3.76], p=0.016), compared with less active GC/CC genotypes in SRD5A2 rs523349. High 5α-reductase activity due to the polymorphism in SRD5A2 may contribute to resistance to ADT. Furthermore, SRD5A2 rs523349 polymorphism may be a promising biomarker for metastatic prostate cancer patients treated with primary ADT and a molecular target for advanced prostate cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Local activity determines functional connectivity in the resting human brain: a simultaneous FDG-PET/fMRI study.

PubMed

Riedl, Valentin; Bienkowska, Katarzyna; Strobel, Carola; Tahmasian, Masoud; Grimmer, Timo; Förster, Stefan; Friston, Karl J; Sorg, Christian; Drzezga, Alexander

2014-04-30

Over the last decade, synchronized resting-state fluctuations of blood oxygenation level-dependent (BOLD) signals between remote brain areas [so-called BOLD resting-state functional connectivity (rs-FC)] have gained enormous relevance in systems and clinical neuroscience. However, the neural underpinnings of rs-FC are still incompletely understood. Using simultaneous positron emission tomography/magnetic resonance imaging we here directly investigated the relationship between rs-FC and local neuronal activity in humans. Computational models suggest a mechanistic link between the dynamics of local neuronal activity and the functional coupling among distributed brain regions. Therefore, we hypothesized that the local activity (LA) of a region at rest determines its rs-FC. To test this hypothesis, we simultaneously measured both LA (glucose metabolism) and rs-FC (via synchronized BOLD fluctuations) during conditions of eyes closed or eyes open. During eyes open, LA increased in the visual system, and the salience network (i.e., cingulate and insular cortices) and the pattern of elevated LA coincided almost exactly with the spatial pattern of increased rs-FC. Specifically, the voxelwise regional profile of LA in these areas strongly correlated with the regional pattern of rs-FC among the same regions (e.g., LA in primary visual cortex accounts for ∼ 50%, and LA in anterior cingulate accounts for ∼ 20% of rs-FC with the visual system). These data provide the first direct evidence in humans that local neuronal activity determines BOLD FC at rest. Beyond its relevance for the neuronal basis of coherent BOLD signal fluctuations, our procedure may translate into clinical research particularly to investigate potentially aberrant links between local dynamics and remote functional coupling in patients with neuropsychiatric disorders.

Virtual lesions of the inferior parietal cortex induce fast changes of implicit religiousness/spirituality.

PubMed

Crescentini, Cristiano; Aglioti, Salvatore M; Fabbro, Franco; Urgesi, Cosimo

2014-05-01

Religiousness and spirituality (RS) are two ubiquitous aspects of human experience typically considered impervious to scientific investigation. Nevertheless, associations between RS and frontoparietal neural activity have been recently reported. However, much less is known about whether such activity is causally involved in modulating RS or just epiphenomenal to them. Here we combined two-pulse (10 Hz) Transcranial Magnetic Stimulation (TMS) with a novel, ad-hoc developed RS-related, Implicit Association Test (IAT) to investigate whether implicit RS representations, although supposedly rather stable, can be rapidly modified by a virtual lesion of inferior parietal lobe (IPL) and dorsolateral prefrontal cortex (DLPFC). A self-esteem (SE) IAT, focused on self-concepts nonrelated to RS representations, was developed as control. A specific increase of RS followed inhibition of IPL demonstrating its causative role in inducing fast plastic changes of religiousness/spirituality. In contrast, DLPFC inhibition had more widespread effects probably reflecting a general role in the acquisition or maintenance of task-rules or in controlling the expression of self-related representations not specific to RS. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Endoplasmic-mitochondrial Ca(2+)-functional unit: dependence of respiration of secretory cells on activity of ryanodine- and IP3 - sensitive Ca(2+)-channels].

PubMed

Velykopols'ka, O Iu; Man'ko, B O; Man'ko, V V

2012-01-01

Using Clark oxygen electrode, dependence of mitochondrial functions on Ca(2+)-release channels activity of Chironomus plumosus L. larvae salivary glands suspension was investigated. Cells were ATP-permeabilized in order to enable penetration of exogenous oxidative substrates. Activation of plasmalemmal P2X-receptors (as well as P2Y-receptors) per se does not modify the endogenous respiration of salivary gland suspension. That is, Ca(2+)-influx from extracellular medium does not influence functional activity of mitochondria, although they are located along the basal part of the plasma membrane. Activation of RyRs intensifies endogenous respiration and pyruvate-malate-stimulated respiration, but not succinate-stimulated respiration. Neither activation of IP3Rs (via P2Y-receptors activation), nor their inhibition alters endogenous respiration. Nevertheless, IP3Rs inhibition by 2-APB intensifies succinate-stimulated respiration. All abovementioned facts testify that Ca2+, released from stores via channels, alters functional activity of mitochondria, and undoubtedly confirm the existence of endoplasmic-mitochondrial Ca(2+)-functional unit in Ch. plumosus larvae salivary glands secretory cells. In steady state of endoplasmic-mitochondrial Ca(2+)-functional unit the spontaneous activity of IP3Rs is observed; released through IP3Rs, Ca2+ is accumulated in mitochondria via uniporter and modulates oxidative processes. Activation of RyRs induces the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to the active state, which is required to intensify cell respiration and oxidative phosphorylation. As expected, the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to inactivated state (i. e. inhibition of Ca(2+)-release channels at excessive [Ca2+]i) limits the duration of signal transduction, has protective nature and prevents apoptosis.

Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells.

PubMed

Losa, G A

2003-09-01

We examined the effect of resveratrol (RS), a nonflavonoid polyphenolic phytoalexin found in grapes and red wine, and RS coincubated with the oxidant 2-deoxy-D-ribose (dR), on apoptosis and on the oxidative metabolic status of normal human peripheral blood mononuclear cells (PBMNCs) isolated ex vivo from healthy donors. Apoptosis was measured by changes of membrane permeability to propidium iodide (PI), plasma membrane exposure of phosphatidylserine (PS) and intracellular caspase activity. Oxidative status was assessed by recording the intracellular glutathione concentration (GSH), the activities of the enzymes y-glutamyltransferase (y-GT) and glutathione-S-transferase (GST), and intracellular lipid peroxidation (MDA). Neither apoptotic nor oxidative parameters were affected by culturing PBMNCs in medium containing RS up to 20 micro M for 5 days, while the frequency of cells with intermediate permeability to PI (17% +/- 5) increased at 50 micro M of RS. Thus resveratrol was slightly toxic, but there was little apoptosis in these cells. Peripheral blood mononuclear cells were also grown first in medium plus RS for 24 h and then for 96 h in medium containing RS plus 10 mM of dR, an oxidant sugar that is apoptogenic for human lymphocytes. The apoptotic changes triggered by dR were counteracted by the phytoalexin in a dose-dependent manner, but RS activity was absent at the lowest concentration (5 micro M) and significantly reduced at the highest concentration used (50 micro M). In PBMNCs coincubated with 20 micro M of RS and 10 mM of dR the antioxidant effect of RS manifested with a significant reduction of caspases-3, -8, y-GT, GST activities and MDA content. Peripheral blood mononuclear cells acquire antioxidant capacity when treated with RS. Grape resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases.

State-dependent, bidirectional modulation of neural network activity by endocannabinoids.

PubMed

Piet, Richard; Garenne, André; Farrugia, Fanny; Le Masson, Gwendal; Marsicano, Giovanni; Chavis, Pascale; Manzoni, Olivier J

2011-11-16

The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.

PubMed

Spoida, Katharina; Masseck, Olivia A; Deneris, Evan S; Herlitze, Stefan

2014-04-29

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice

PubMed Central

Spoida, Katharina; Masseck, Olivia A.; Deneris, Evan S.; Herlitze, Stefan

2014-01-01

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice. PMID:24733892

CVN’s, is Eleven Too Many or Too Few?

DTIC Science & Technology

2011-03-10

allows for transit and work ups for deployment. The complete cycle has one ship on post, one corning off post and one preparing to take post in each of...developed the Silk Missile, an. anti -ship missile that can sink a smaller vessel with one burst. Many of the defenses used in the modem carrier

Visualization of the Flow Field around an Oscillating Model of the USS Enterprise (CVN-65) in a Simulated Atmospheric Boundary Layer

DTIC Science & Technology

1988-03-01

visualization tunnel. The tunnel is of the open circuit type and it draws air into 9 j•;•.,p~ ~ ~ ~ ~~~~~~~~~.... ..•,"r• • •• IWLT - ’ ’•1•• ••!•• • the

α4α6β2* nicotinic acetylcholine receptor activation on ventral tegmental area dopamine neurons is sufficient to stimulate a depolarizing conductance and enhance surface AMPA receptor function.

PubMed

Engle, Staci E; Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

2013-09-01

Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in ventral tegmental area (VTA) dopamine (DA) neurons are crucial for the rewarding and reinforcing properties of nicotine in rodents, suggesting that they may be key mediators of nicotine's action in humans. However, it is unknown which nAChR subtypes are sufficient to activate these neurons. To test the hypothesis that nAChRs containing α6 subunits are sufficient to activate VTA DA neurons, we studied mice expressing hypersensitive, gain-of-function α6 nAChRs (α6L9'S mice). In voltage-clamp recordings in brain slices from adult mice, 100 nM nicotine was sufficient to elicit inward currents in VTA DA neurons via α6β2* nAChRs. In addition, we found that low concentrations of nicotine could act selectively through α6β2* nAChRs to enhance the function of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors on the surface of these cells. In contrast, α6β2* activation did not enhance N-methyl-D-aspartic acid receptor function. Finally, AMPA receptor (AMPAR) function was not similarly enhanced in brain slices from α6L9'S mice lacking α4 nAChR subunits, suggesting that α4α6β2* nAChRs are important for enhancing AMPAR function in VTA DA neurons. Together, these data suggest that activation of α4α6β2* nAChRs in VTA DA neurons is sufficient to support the initiation of cellular changes that play a role in addiction to nicotine. α4α6β2* nAChRs may be a promising target for future smoking cessation pharmacotherapy.

Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery.

PubMed

González-Cestari, Tatiana F; Henderson, Brandon J; Pavlovicz, Ryan E; McKay, Susan B; El-Hajj, Raed A; Pulipaka, Aravinda B; Orac, Crina M; Reed, Damon D; Boyd, R Thomas; Zhu, Michael X; Li, Chenglong; Bergmeier, Stephen C; McKay, Dennis B

2009-02-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of alpha3beta4(*) nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant alpha3beta4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native alpha3beta4(*) nAChR, with IC(50) values ranging from 0.4 to 13.0 microM. Using cells expressing recombinant alpha3beta4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC(50) values ranging from 0.7 to 38.2 microM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 microM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery.

Effect of Novel Negative Allosteric Modulators of Neuronal Nicotinic Receptors on Cells Expressing Native and Recombinant Nicotinic Receptors: Implications for Drug Discovery

PubMed Central

González-Cestari, Tatiana F.; Henderson, Brandon J.; Pavlovicz, Ryan E.; McKay, Susan B.; El-Hajj, Raed A.; Pulipaka, Aravinda B.; Orac, Crina M.; Reed, Damon D.; Boyd, R. Thomas; Zhu, Michael X.; Li, Chenglong; Bergmeier, Stephen C.; McKay, Dennis B.

2009-01-01

Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of α3β4* nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant α3β4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native α3β4* nAChR, with IC50 values ranging from 0.4 to 13.0 μM. Using cells expressing recombinant α3β4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC50 values ranging from 0.7 to 38.2 μM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 μM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery. PMID:18984653

Novel Nrf2 activators from microbial transformation products inhibit blood-retinal barrier permeability in rabbits.

PubMed

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-03-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood-retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. © 2014 The British Pharmacological Society.

Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits

PubMed Central

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-01-01

Background and Purpose Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. Experimental Approach The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood–retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Key Results Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Conclusion and Implications Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. PMID:25363737

Application of the Transtheoretical Model of behavior change to the physical activity behavior of WIC mothers.

PubMed

Fahrenwald, Nancy L; Walker, Susan Noble

2003-01-01

This descriptive-correlational study examined the Transtheoretical Model (TTM) of behavior change in relationship to the physical activity behavior of mothers receiving assistance from the Women, Infants, and Children program. A purposive sample (N = 30) of six women at each of the five stages of readiness for behavior change was used. Relationships between stage of behavior change (measured using the Stage of Exercise Adoption tool) and other TTM constructs were examined. The constructs and corresponding instruments included physical activity behavior (Seven-Day Physical Activity Recall), pros, cons, decisional balance (Exercise Benefits/Barriers Scale and two open-ended questions), self-efficacy (Self-efficacy for Exercise scale), and processes of behavior change (Processes of Exercise Adoption tool and the Social Support for Exercise scale). Significant relationships were found between stage of behavior change and two physical activity energy expenditure indices (rs = 0.71-0.73, p < 0.01), daily minutes of moderate to very hard physical activity (rs = 0.81, p < 0.01), pros (rs = 0.56, p < 0.01), cons (rs = -0.52, p < 0.05), decisional balance (rs = 0.56, p < 0.01), and self-efficacy (rs = 0.56, p < 0.01). Use of the 10 processes of change differed by stage of change. Pros to physical activity included a sense of accomplishment, increased strength, stress relief, and getting in shape after pregnancy. Cons included fatigue, childcare, and cold weather. Results support the TTM as relevant to WIC mothers and suggest strategies to increase physical activity in this population.

Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns.

PubMed

Finarov, Igal; Moor, Nina; Kessler, Naama; Klipcan, Liron; Safro, Mark G

2010-03-10

The existence of three types of phenylalanyl-tRNA synthetase (PheRS), bacterial (alphabeta)(2), eukaryotic/archaeal cytosolic (alphabeta)(2), and mitochondrial alpha, is a prominent example of structural diversity within the aaRS family. PheRSs have considerably diverged in primary sequences, domain compositions, and subunit organizations. Loss of the anticodon-binding domain B8 in human cytosolic PheRS (hcPheRS) is indicative of variations in the tRNA(Phe) binding and recognition as compared to bacterial PheRSs. We report herein the crystal structure of hcPheRS in complex with phenylalanine at 3.3 A resolution. A novel structural module has been revealed at the N terminus of the alpha subunit. It stretches out into the solvent of approximately 80 A and is made up of three structural domains (DBDs) possessing DNA-binding fold. The dramatic reduction of aminoacylation activity for truncated N terminus variants coupled with structural data and tRNA-docking model testify that DBDs play crucial role in hcPheRS activity.

Correlations between ACE single nucleotide polymorphisms and prognosis of patients with septic shock.

PubMed

Dou, Xin-Man; Cheng, Hui-Juan; Meng, Ling; Zhou, Lin-Lin; Ke, Yi-Hong; Liu, Li-Ping; Li, Yu-Min

2017-04-30

The aim of the present study is to investigate association between septic shock (SS) and angiotensin I-converting enzyme ( ACE ) single nucleotide polymorphisms (SNPs). From October 2009 to December 2016, 238 SS patients and 242 healthy individuals were selected for our study. ACE activity was detected, ACE rs4291 and rs4646994 polymorphisms were detected using PCR-restriction fragment length polymorphism (PCR-RFLP). The Kaplan-Meier survival curve was employed to evaluate the association between ACE SNPs and patients' survival and univariate and multivariate analyses to estimate risk factors for SS. ACE activity in the case group was increased in comparison with the control group. Allele and genotype frequencies of rs4291 and rs4646994 were different between the case and control groups. The TT genotype frequency of the rs4291 polymorphisms and the DD genotype of the rs4646994 polymorphisms of the case group were higher than those in the control group. The AT and TT genotypes indicated a significant elevation of ACE activity than the AA genotype, while a significant decline was found in the DI and II genotypes in comparison with the DI genotype. Patients with TT or DD genotypes had increased fatality rate within 7 and 30 days when compared with those with non-TT or non-DD genotypes. Lower sepsis-related organ failure assessment (SOFA) scores, rs4291, serum ACE and rs4646994 were all considered as risky factors for SS patients. The study demonstrates that TT genotype of rs4291 or DD genotype of rs4646994 may be indicative of a higher risk of SS and a poorer prognosis in SS patients. © 2017 The Author(s).

[Association between GSK3β polymorphisms and the smoking habits in young Japanese].

PubMed

Nagahori, Kenta; Iwahashi, Kazuhiko; Narita, Shin; Numajiri, Maki; Yoshihara, Eiji; Nishizawa, Daisuke; Ikeda, Kazutaka; Ishigooka, Jun

2015-06-01

Schizophrenia and bipolar disorder show high comorbidity with smoking dependence. Several previous studies reported that glycogen synthase kinase 3β (GSK3β), which is widely expressed in the brain including the dopamine projection areas such as the amygdala, nucleus accumbens and hippocampus, may play a role in neuropsychiatric disorders and dopamine- and serotonin-mediated behavior. In this study, we have analyzed the association of three single nucleotide polymorphisms (SNPs) within GSK3β gene (rs3755557, rs334558, rs6438552) with the smoking habits and age at smoking initiation in a sample of 384 young adult Japanese, which included 172 smokers and 212 non-smokers. As a result, rs334558 was significantly associated with smoking habits in genotype frequency and allelic frequency (P < 0.05). Furthermore, higher haplotype 3 (T-T-T) and haplotype 5 (A-T-C) frequencies were observed in non-smokers than smokers (P < 0.05). Three functional polymorphisms examined in this study reportedly increase transcriptional activity when they have a high-activation allele such as the A allele of -1727A/T (rs3755557), the T allele of -50T/C (rs334558) or T allele of -157T/C (rs6438552). Thus, it was suggested in this study that changes in GSK3β activity may have an impact on smoking habits.

A comparison of RS4-type resistant starch to RS2-type resistant starch in suppressing oxidative stress in high-fat-diet-induced obese rats.

PubMed

Si, Xu; Zhou, Zhongkai; Strappe, Padraig; Blanchard, Chris

2017-01-25

The anti-obesity effects of two types of resistant starch (RS) in high-fat-diet-induced obese rats were investigated. The serum triglycerides, total cholesterol and malondialdehyde concentrations were significantly reduced, and the total antioxidant capacity, superoxide dismutase levels and glutathione peroxidase activity were increased by RS2 and RS4 consumption compared to the obesity group. A significant reduction in the serum glucose level and elevations in hepatic lipid metabolic enzyme activities were observed only for RS4 administration. Moreover, the expression levels of the fatty acid synthesis associated genes ACC and Fads1, the triglyceride synthesis and metabolism-related gene SREBP-1, the adipocyte differentiation gene PPARγ, the cholesterol synthesis associated gene HMGCR, and the gluconeogenesis associated gene GAPDH were all significantly down-regulated, whilst the lipid oxidation gene Acox1 and the liver function genes Gsta2, Nqo1, and Gclm were up-regulated in both administered groups. Additionally, RS4 performed well in up-regulating the expressions of Gsta2, Gsta3, Nqo1, and Egfr, and down-regulating LXRα, Igfbp1, and Pml. RS4 exhibited great advantages in reducing oxidative stress compared with RS2.

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

PubMed

Bank, S; Andersen, P S; Burisch, J; Pedersen, N; Roug, S; Galsgaard, J; Turino, S Y; Brodersen, J B; Rashid, S; Rasmussen, B K; Avlund, S; Olesen, T B; Hoffmann, H J; Nexø, B A; Sode, J; Vogel, U; Andersen, V

2018-01-01

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

The Catalina Surveys Southern periodic variable star catalogue

NASA Astrophysics Data System (ADS)

Drake, A. J.; Djorgovski, S. G.; Catelan, M.; Graham, M. J.; Mahabal, A. A.; Larson, S.; Christensen, E.; Torrealba, G.; Beshore, E.; McNaught, R. H.; Garradd, G.; Belokurov, V.; Koposov, S. E.

2017-08-01

Here, we present the results from our analysis of 6 yr of optical photometry taken by the Siding Spring Survey (SSS). This completes a search for periodic variable stars within the 30 000 deg2 of the sky covered by the Catalina Surveys. The current analysis covers 81 million sources with declinations between -20° and -75° with median magnitudes in the range 11 < V < 19.5. We find approximately 34 000 new periodic variable stars in addition to the ˜9000 RR Lyrae that we previously discovered in SSS data. This brings the total number of periodic variables identified in Catalina data to ˜110 000. The new SSS periodic variable stars mainly consist of eclipsing binaries, RR Lyrae, LPVs, RS CVn stars, δ Scutis, and Anomalous Cepheids. By cross-matching these variable stars with those from prior surveys, we find that ˜90 per cent of the sources are new discoveries and recover ˜95 per cent of the known periodic variables in the survey region. For the known sources, we find excellent agreement between our catalogue and prior values of luminosity, period, and amplitude. However, we find many variable stars that had previously been misclassified. Examining the distribution of RR Lyrae, we find a population associated with the Large Magellanic Cloud (LMC) that extends more than 20° from its centre confirming recent evidence for the existence of a very extended stellar halo in the LMC. By combining SSS photometry with Dark Energy Survey data, we identify additional LMC halo RR Lyrae, thus confirming the significance of the population.

The first search for variable stars in the open cluster NGC 6253 and its surrounding field

NASA Astrophysics Data System (ADS)

de Marchi, F.; Poretti, E.; Montalto, M.; Desidera, S.; Piotto, G.

2010-01-01

Aims: This work presents the first high-precision variability survey in the field of the intermediate-age, metal-rich open cluster NGC 6253. Clusters of this type are benchmarks for stellar evolution models. Methods: Continuous photometric monitoring of the cluster and its surrounding field was performed over a time span of ten nights using the Wide Field Imager mounted at the ESO-MPI 2.2 m telescope. High-quality timeseries, each composed of about 800 datapoints, were obtained for 250 000 stars using ISIS and DAOPHOT packages. Candidate members were selected by using the colour-magnitude diagrams and period-luminosity-colour relations. Membership probabilities based on the proper motions were also used. The membership of all the variables discovered within a radius of 8´ from the centre is discussed by comparing the incidence of the classes in the cluster direction and in the surrounding field. Results: We discovered 595 variables and we also characterized most of them providing their variability classes, periods, and amplitudes. The sample is complete for short periods: we classified 20 pulsating variables, 225 contact systems, 99 eclipsing systems (22 β Lyr type, 59 β Per type, 18 RS CVn type), and 77 rotational variables. The time-baseline hampered the precise characterization of 173 variables with periods longer than 4-5 days. Moreover, we found a cataclysmic system undergoing an outburst of about 2.5 mag. We propose a list of 35 variable stars as probable members of NGC 6253. ARRAY(0x383c870)

Rotational modulation and flares on RS CVn and BY DRA systems. VIII - Simultaneous EXOSAT and H-alpha observations of a flare on the dMe star GL 644 AB (Wolf 630) on 24/25 August 1985

NASA Astrophysics Data System (ADS)

Doyle, J. G.; Butler, C. J.; Callanan, P. J.; Tagliaferri, G.; de La Reza, R.; White, N. E.; Torres, C. A.; Quast, G.

1988-02-01

A large flare was detected simultaneously in X-rays and H-alpha on the visual binary Gl 644 AB at about 00:15 UT on August 25, 1985. The flare was detected with both the low (0.05-2 keV) and medium energy (2-7 keV) experiments onboard Exosat, with the flare rise time being similar in both the low and medium energy ranges, although in the low energy the peak occurred about 30 s later. This was followed a few minutes later by a second burst. The flare decay time lasted about 10 minutes longer in the low energy band than in the medium energy. The integrated flare energy detected was 11.9 x 10 to the 32nd and 4.15 x 10 to the 32nd erg respectively in the low and medium energy X-rays and 7 x 10 to the 31st erg in H-alpha. This gives an H-alpha flux of approximately 4 percent of the total X-ray flux detected from the flare or 6 percent of the low X-ray flare energy, similar to that observed in a compact solar flare. Based on the observed cooling time, the flare was estimated to have 2-3 loops of height about 10 to the 9th cm and electron density of about 10 to the 12th/cu cm.

RgIA4 Potently Blocks Mouse α9α10 nAChRs and Provides Long Lasting Protection against Oxaliplatin-Induced Cold Allodynia.

PubMed

Christensen, Sean B; Hone, Arik J; Roux, Isabelle; Kniazeff, Julie; Pin, Jean-Philippe; Upert, Grégory; Servent, Denis; Glowatzki, Elisabeth; McIntosh, J Michael

2017-01-01

Transcripts for α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are found in diverse tissues. The function of α9α10 nAChRs is best known in mechanosensory cochlear hair cells, but elsewhere their roles are less well-understood. α9α10 nAChRs have been implicated as analgesic targets and α-conotoxins that block α9α10 nAChRs produce analgesia. However, some of these peptides show large potency differences between species. Additionally several studies have indicated that these conotoxins may also activate GABA B receptors (GABA B Rs). To further address these issues, we cloned the cDNAs of mouse α9 and α10 nAChR subunits. When heterologously expressed in Xenopus oocytes, the resulting α9α10 nAChRs had the expected pharmacology of being activated by acetylcholine and choline but not by nicotine. A conotoxin analog, RgIA4, potently, and selectively blocked mouse α9α10 nAChRs with low nanomolar affinity indicating that RgIA4 may be effectively used to study murine α9α10 nAChR function. Previous reports indicated that RgIA4 attenuates chemotherapy-induced cold allodynia. Here we demonstrate that RgIA4 analgesic effects following oxaliplatin treatment are sustained for 21 days after last RgIA4 administration indicating that RgIA4 may provide enduring protection against nerve damage. RgIA4 lacks activity at GABA B receptors; a bioluminescence resonance energy transfer assay was used to demonstrate that two other analgesic α-conotoxins, Vc1.1 and AuIB, also do not activate GABA B Rs expressed in HEK cells. Together these findings further support the targeting of α9α10 nAChRs in the treatment of pain.

Methamphetamine reduces expression of caveolin-1 in the dorsal striatum: Implication for dysregulation of neuronal function.

PubMed

Somkuwar, Sucharita S; Fannon, McKenzie J; Head, Brian P; Mandyam, Chitra D

2016-07-22

Role of striatal dopamine D1 receptors (D1Rs) in methamphetamine (Meth) taking and seeking is recognized from contingent Meth self-administration studies. For example, Meth increases levels of D1Rs in the dorsal striatum in animal models of Meth addiction, and blockade of striatal D1Rs decreased responding for Meth and reduced Meth priming-induced drug seeking. However, the mechanism underlying enhanced expression of striatal D1Rs in animals self-administering Meth is unknown and is hypothesized to involve maladaptive intracellular signal transduction mechanism via hyperphosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). D1Rs are predominantly localized to detergent-resistant membrane/lipid raft fractions (MLR fraction), and in vitro studies indicate that D1R signaling and recycling is regulated by the MLR-resident protein caveolin-1 (Cav-1), in an endocytotic-dependent manner. Notably, expression of Cav-1 is inversely regulated by ERK1/2 activation, suggesting a signaling interplay among D1Rs, ERK1/2 and Cav-1. We therefore evaluated the effects of extended access Meth self-administration on expression of striatal D1Rs, activated ERK1/2 and Cav-1. We first report that Cav-1 is heavily expressed in neurons located in the dorsal striatum. We also report that extended access Meth produces compulsive-like unregulated intake of the drug, and these behavioral outcomes are associated with enhanced expression of D1Rs, increased activity of ERK1/2, and reduced Cav-1 expression in the dorsal striatum. These data suggest a possible cellular mechanism that involves Cav-1 regulation of D1R expression in response to escalated Meth intake, and how this response of altered D1Rs and enhanced ERK1/2 activation to Meth self-administration contributes to contingent-related processes such as addiction. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Methamphetamine reduces expression of caveolin-1 in the dorsal striatum: implication for dysregulation of neuronal function

PubMed Central

Somkuwar, Sucharita S.; Fannon, McKenzie J.; Head, Brian P.; Mandyam, Chitra D.

2016-01-01

Role of striatal dopamine D1 receptors (D1Rs) in methamphetamine (Meth) taking and seeking is recognized from contingent Meth self-administration studies. For example, Meth increases levels of D1Rs in the dorsal striatum in animal models of Meth addiction, and blockade of striatal D1Rs decreased responding for Meth and reduced Meth priming-induced drug seeking. However, the mechanism underlying enhanced expression of striatal D1Rs in animals self-administering Meth is unknown and is hypothesized to involve maladaptive intracellular signal transduction mechanism via hyperphosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). D1Rs are predominantly localized to detergent-resistant membrane/lipid raft fractions (MLR fraction), and in vitro studies indicate that D1R signaling and recycling is regulated by the MLR-resident protein caveolin-1 (Cav-1), in an endocytotic-dependent manner. Notably, expression of Cav-1 is inversely regulated by ERK1/2 activation, suggesting a signaling interplay among D1Rs, ERK1/2 and Cav-1. We therefore evaluated the effects of extended access Meth self-administration on expression of striatal D1Rs, activated ERK1/2 and Cav-1. We first report that Cav-1 is heavily expressed in neurons located in the dorsal striatum. We also report that extended access Meth produces compulsive-like unregulated intake of the drug, and these behavioral outcomes are associated with enhanced expression of D1Rs, increased activity of ERK1/2, and reduced Cav-1 expression in the dorsal striatum. These data suggest a possible cellular mechanism that involves Cav-1 regulation of D1R expression in response to escalated Meth intake, and how this response of altered D1Rs and enhanced ERK1/2 activation to Meth self-administration contributes to contingent-related processes such as addiction. PMID:27138644

Regulation of a glutamyl-tRNA synthetase by the heme status

PubMed Central

Levicán, Gloria; Katz, Assaf; de Armas, Merly; Núñez, Harold; Orellana, Omar

2007-01-01

Glutamyl-tRNA (Glu-tRNA), formed by Glu-tRNA synthetase (GluRS), is a substrate for protein biosynthesis and tetrapyrrole formation by the C5 pathway. In this route Glu-tRNA is transformed to δ-aminolevulinic acid, the universal precursor of tetrapyrroles (e.g., heme and chlorophyll) by the action of Glu-tRNA reductase (GluTR) and glutamate semialdehyde aminotransferase. GluTR is a target of feedback regulation by heme. In Acidithiobacillus ferrooxidans, an acidophilic bacterium that expresses two GluRSs (GluRS1 and GluRS2) with different tRNA specificity, the intracellular heme level varies depending on growth conditions. Under high heme requirement for respiration increased levels of GluRS and GluTR are observed. Strikingly, when intracellular heme is in excess, the cells respond by a dramatic decrease of GluRS activity and the level of GluTR. The recombinant GluRS1 enzyme is inhibited in vitro by hemin, but NADPH restores its activity. These results suggest that GluRS plays a major role in regulating the cellular level of heme. PMID:17360620

Optical resolution by preferential crystallization of (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid and its use in synthesizing optically active 2-amino-2-methyl-3-phenylpropanoic acid.

PubMed

Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji

2002-10-01

To synthesize optically active 2-amino-2-methyl-3-phenylpropanoic acid (1), (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid [(RS)-2] was first optically resolved using cinchonidine as a resolving agent to yield optically pure (S)- and (R)-2 in yields of about 70%, based on half of the starting amount of (RS)-2. Next, the racemic structure of (RS)-2 was examined based on melting point, solubility, IR spectrum, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-2. Results indicated that the (RS)-2 exists as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization yielded (S)- and (R)-2 with optical purities of about 90%, which were fully purified by recrystallization. After O-tosylation of (S)- and (R)-2, reduction by zinc powder and sodium iodide gave (R)- and (S)-1, respectively.

PTM Modeling of Dredged Suspended Sediment at Proposed Polaris Point and Ship Repair Facility CVN Berthing Sites - Apra Harbor, Guam

DTIC Science & Technology

2017-09-01

ADCP locations used for model calibration. ......................................................................... 12 Figure 4-3. Sample water...Example of fine sediment sample [Set d, Sample B30]. (B) Example of coarse sediment sample [Set d, sample B05...Turning Basin average sediment size distribution curve. ................................................... 21 Figure 5-5. Turning Basin average size

Underkeel Clearance Study.

DTIC Science & Technology

1981-09-01

EnterewJ N00014-80-C-0395 CONTENTS Page EXECUTIVE SUMMARY 1.0 INTRODUCTION 1.1 The Underlying Problem ................. 1-1 1.2 The Current Study...3-4 3.2.4 CVN Berthinq Facilities .................... 3-4 ii! JI N00014-80-C-0395 CONTENTS (continued) 3.3 Hydrologic Conditions...Drafts ...................... 3-10 3.8.3 Underkeel Clearance ........ .............. 3-10 4.0 THE ANALYSIS 4.1 The Physical Model

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

DTIC Science & Technology

2016-05-27

the start-stop-start-stop cycle over a stretched period of time and that’s a big cost impact . But the challenge is by the same token, the build cycle...well as trying to balance the impacts on geographic locations. Q: What will happen to the aircraft from the eliminated squadrons? A: Where applicable

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

DTIC Science & Technology

2016-05-27

the start-stop-start-stop cycle over a stretched period of time and that’s a big cost impact . But the challenge is by the same token, the build cycle...well as trying to balance the impacts on geographic locations. Q: What will happen to the aircraft from the eliminated squadrons? A: Where applicable

Northwest Manufacturing Initiative

DTIC Science & Technology

2013-03-26

Testing of Metallic Materials] specifications. For high temperature tests, a heated water bath was use while for low temperature testing down to...Weld metal and heat affected zones were evaluated using Charpy and E399 fracture toughness methods. The influence of temperature , loading rate, CVN...determine the influence of fracture test methods and welding procedures on toughness. Room temperature E399 tests, (CTS) were carried out under

Organizational Analysis of Food Service Management

DTIC Science & Technology

2011-06-01

35  d.  Senior Culinary Specialists on “Twilight” Tour ...................35  e.  NAVSUP Controls Quality of Life...Supply Centers COMSUBFOR Commander Submarine Force CS Culinary Specialist CSCS Culinary Specialist Senior Chief CVN Carrier Vessel Nuclear DDG Guided...attention of the Culinary Specialists. The type of assist visit can be tailored to the requirements identified by the requesting command. Normally

Microstructure and Mechanical Properties of a Low Alloyed MnB Cast Steel

NASA Astrophysics Data System (ADS)

Luo, Kaishuang; Bai, Bingzhe

2010-08-01

The microstructure and mechanical properties of a low alloyed MnB cast steel designed for coupler castings of trucks were studied. The results show that the microstructure of the MnB cast steel after water quenching is lath martensite and a small amount of massive islands in the matrix of lath martensite. The average size of the martensite packets is about 10 μm in length. Carbides precipitated dispersively at the tempering temperature of 450 °C. The carbides are slender and fibrous, of which the microstructure was θ-phase (Fe, Mn)3C characterized by TEM. The MnB cast steel has good hardenability and tempering stability. Excellent combination of strength, ductility and low-temperature toughness were obtained after water-quenching and 450 °C tempering: Rm = 960-1040 MPa, ReL = 880-900 MPa, A = 19-21%, Z = 56-58%. Especially, the impact energy of the Charpy V-Notch (CVN) specimens reached 70-88 J at -40 °C. The fracture mechanism is transcrystalline fracture both for ambient temperature uniaxial tensile test specimens and for CVN impact test specimens broken at -40 °C, where the whole surfaces were manifested as voids and dimples.

A modified correlation between KJIC and Charpy V-notch impact energy of Chinese SA508-III steel at the upper shelf

NASA Astrophysics Data System (ADS)

Li, Xiangqing; Song, Yuxuan; Ding, Zhenyu; Bao, Shiyi; Gao, Zengliang

2018-07-01

The fracture toughness plays a significant role in the structural integrity assessment of reactor pressure vessels (RPVs) in service temperature. The Charpy V-notch (CVN) impact test is used to estimate fracture toughness (KIC or KJIC) indirectly since universal fracture toughness tests are costly, sophisticated and frequently invalid. In this study, a modified correlation which based on the typical model of KJIC-CVN at the upper shelf was established for Chinese SA508-III steel. Thereinto, the effect of test temperature (T) was directly considered in the correlation. To assess the accuracy of fracture toughness when calculating from the value of Charpy-V notch impact energy by using the modified correlation, both the Charpy-V notch impact tests and fracture toughness tests for Chinese SA508-III steel were conducted at different temperatures (100 °C, 150 °C, 200 °C, 250 °C and 320 °C). The results showed that the modified correlation exhibited the high precision for estimating fracture toughness of Chinese SA508-III steel and the relative error for tested and estimated results is within 8%, which is lower than that of other correlations.

[Increased content of nucleotide sequences in transcriptionally active DNA and poly(A)+-mRNA of the rat liver and a rise in its translation activity as affected by inducers].

PubMed

Dashkevich, V S; Vishnivetskiĭ, S N; Skobel'tsina, L M; Luk'ianchikova, N L; Kaledin, V I

1986-12-01

Cortisol and 3'-methyl-4-dimethyl-amino-azobenzene induce an increase in the content of repeated sequences (RS) in transcriptionally active (TA) DNA, while the content of respective RS in potentially active DNA fractions enriched with regulatory regions of the genome decreases. RS content in induced poly A+-mRNA also rises, as determined by the nature of hybridization of respective c DNA with total DNA. The translation of induced poly A+-mRNA rises essentially, with the qualitative distinctions in in vitro synthesized protein product spectrum being absent. Inducible RS with unstable chromatine conformation are thought to provide a universal system of rapid response of the genetic apparatus to extreme situations, serving as transcription intensifiers in TA DNA and as translation intensifiers in induced poly A+-mRNA.

Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract.

PubMed

Yang, Jing-Ming; Jiang, Hua; Dai, Hong-Liang; Wang, Zi-Wei; Jia, Gui-Zhi; Meng, Xiang-Cai

2016-09-06

Vegetative but not reproductive stage of Saposhnikovia divaricate (Turxz.) schischk possesses pharmacological activities. However, our recent study showed that reproductive S. divaricate supplemented with polysaccharide showed evidently elevated pharmacological activities and increased cimifugin content in rat serum. The aims of present study were to assess the influence of polysaccharides on the chromones pharmacological activities in Radix Saposhnikoviae (RS), the dried root of vegetative stage of S. divaricate, and to explore the underlying mechanisms. Only cimifugin was detected in the plasma of chromone treated animals and RS polysaccharide significantly increased the plasma content of cimifugin. It was shown that neither cimifugin absorption nor glycoside components transformation in simulated digestive fluid was affected by RS polysaccharide. However, a significant promotion of transformation of cimifugin to more stable prime-O-glucosylcimifugin (PGCN) by RS polysaccharide, and a protective effect of polysaccharide on chromone components were observed in small intestine solutions. Meanwhile, RS polysaccharide produced a significant elevation of cimifugin and PGCN concentration in vivo. Based on these findings, we concluded that RS polysaccharide could greatly increase the content of cimifugin, which might be related to its degradation-proof effect on cimifugin, via transforming cimifugin to comparatively more stable PGCN and spatial structure protection.

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

Phillips, Claire L.; Bond-Lamberty, Ben; Desai, Ankur R.

A recent acceleration of model-data synthesis activities has leveraged many terrestrial carbon (C) datasets, but utilization of soil respiration (RS) data has not kept pace with other types such as eddy covariance (EC) fluxes and soil C stocks. Here we argue that RS data, including non-continuous measurements from survey sampling campaigns, have unrealized value and should be utilized more extensively and creatively in data synthesis and modeling activities. We identify three major challenges in interpreting RS data, and discuss opportunities to address them. The first challenge is that when RS is compared to ecosystem respiration (RECO) measured from EC towers,more » it is not uncommon to find substantial mismatch, indicating one or both flux methodologies are unreliable. We argue the most likely cause of mismatch is unreliable EC data, and there is an unrecognized opportunity to utilize RS for EC quality control. The second challenge is that RS integrates belowground heterotrophic (RH) and autotrophic (RA) activity, whereas modelers generally prefer partitioned fluxes, and few models include an explicit RS output. Opportunities exist to use the total RS flux for data assimilation and model benchmarking methods rather than less-certain partitioned fluxes. Pushing for more experiments that not only partition RS but also monitor the age of RA and RH, as well as for the development of belowground RA components in models, would allow for more direct comparison between measured and modeled values. The third challenge is that soil respiration is generally measured at a very different resolution than that needed for comparison to EC or ecosystem- to global-scale models. Measuring soil fluxes with finer spatial resolution and more extensive coverage, and downscaling EC fluxes to match the scale of RS, will improve chamber and tower comparisons. Opportunities also exist to estimate RH at regional scales by implementing decomposition functional types, akin to plant functional types. We conclude by discussing the benefits that wide use of RS data will bring to model development, and database developments that will make RS data more robust, useful, and broadly available to the research community.« less

Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A.

PubMed

Jagielo, P J; Quinn, T J; Qureshi, N; Schwartz, D A

1998-01-01

To further determine the importance of endotoxin in grain dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides (RsDPLA) as a partial agonist of grain dust-induced airway inflammation. RsDPLA is a relatively inactive compound compared with lipid A derived from Escherichia coli (LPS) and has been demonstrated to act as a partial agonist of LPS-induced inflammation. To assess the potential stimulatory effect of RsDPLA in relation to LPS, we incubated THP-1 cells with RsDPLA (0.001-100 micrograms/ml), LPS (0.02 microgram endotoxin activity/ml), or corn dust extract (CDE; 0.02 microgram endotoxin activity/ml). Incubation with RsDPLA revealed a tumor necrosis factor (TNF)-alpha stimulatory effect at 100 micrograms/ml. In contrast, incubation with LPS or CDE resulted in TNF-alpha release at 0.02 microgram/ml. Pretreatment of THP-1 cells with varying concentrations of RsDPLA before incubation with LPS or CDE (0.02 microgram endotoxin activity/ml) resulted in a dose-dependent reduction in the LPS- or CDE-induced release of TNF-alpha with concentrations of RsDPLA of up to 10 micrograms/ml but not at 100 micrograms/ml. To further understand the role of endotoxin in grain dust-induced airway inflammation, we utilized the unique LPS inhibitory property of RsDPLA to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. Ten micrograms of RsDPLA intratracheally did not cause a significant inflammatory response compared with intratracheal saline. However, pretreatment of mice with 10 micrograms of RsDPLA intratracheally before exposure to CDE (5.4 and 0.2 micrograms/m3) or LPS (7.2 and 0.28 micrograms/m3) resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. These results confirm the LPS-inhibitory effect of RsDPLA and support the role of endotoxin as the principal agent in grain dust causing airway inflammation.

Backyard Telescopes Watch an Expanding Binary

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2018-01-01

What can you do with a team of people armed with backyard telescopes and a decade of patience? Test how binary star systems evolve under Einsteins general theory of relativity!Unusual VariablesCataclysmic variables irregularly brightening binary stars consisting of an accreting white dwarf and a donor star are a favorite target among amateur astronomers: theyre detectable even with small telescopes, and theres a lot we can learn about stellar astrophysics by observing them, if were patient.Diagram of a cataclysmic variable. In an AM CVn, the donor is most likely a white dwarf as well, or a low-mass helium star. [Philip D. Hall]Among the large family of cataclysmic variables is one unusual type: the extremely short-period AM Canum Venaticorum (AM CVn) stars. These rare variables (only 40 are known) are unique in having spectra dominated by helium, suggesting that they contain little or no hydrogen. Because of this, scientists have speculated that the donor stars in these systems are either white dwarfs themselves or very low-mass helium stars.Why study AM CVn stars? Because their unusual configuration allows us to predict the behavior of their orbital evolution. According to the general theory of relativity, the two components of an AM CVn will spiral closer and closer as the system loses angular momentum to gravitational-wave emission. Eventually they will get so close that the low-mass companion star overflows its Roche lobe, beginning mass transfer to the white dwarf. At this point, the orbital evolution will reverse and the binary orbit will expand, increasing its period.CBA member Enrique de Miguel, lead author on the study, with his backyard telescope in Huelva, Spain. [Enrique de Miguel]Backyard Astronomy Hard at WorkMeasuring the evolution of an AM CVns orbital period is the best way to confirm this model, but this is no simple task! To observe this evolution, we first need a system with a period that can be very precisely measured best achieved with an eclipsing binary system. Then the system must be observed regularly over a very long period of time.Though such a feat is challenging, a team of astronomers has done precisely this. The Center for Backyard Astrophysics (CBA) a group of primarily amateur astronomers located around the world has collectively observed the AM CVn star system ES Ceti using seven different telescopes over more than a decade. In total, they now have measurements of ES Cetis period spanning 20012017. Now, in a publication led by Enrique de Miguel (CBA-Huelva and University of Huelva, Spain), the group details the outcomes of their patience.Testing the ModelThis OC diagram of the timings of minimum light relative to a test ephemeris demonstrates that ES Cetis orbital period is steadily increasing over time. [de Miguel et al. 2017]De Miguel and collaborators find that ES Cetis 10.3-minute orbital period has indeed increased over time as predicted by the model at a relatively rapid rate: the timescale for change, described by P/(dP/dt), is 10 million years. This outcome is consistent with the hypothesis that the mass transfer and binary evolution of such systems is driven by gravitational radiation marking one of the first such demonstrations with a cataclysmic variable.Whats next for ES Ceti? Systems such as this one will make for interesting targets for the Laser Interferometer Space Antenna (LISA; planned for a 2034 launch). The gravitational radiation emitted by AM CVns like ES Ceti should be strong enough and in the right frequency range to be detected by LISA, providing another test of our models for how these star systems evolve.CitationEnrique de Miguel et al 2018 ApJ 852 19. doi:10.3847/1538-4357/aa9ed6

Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study.

PubMed

Dobrinas, Maria; Crettol, Séverine; Oneda, Beatrice; Lahyani, Rachel; Rotger, Margalida; Choong, Eva; Lubomirov, Rubin; Csajka, Chantal; Eap, Chin B

2013-02-01

(S)-Methadone, metabolized mainly by CYP2B6, shows a wide interindividual variability in its pharmacokinetics and pharmacodynamics. Resequencing of the CYP2B6 gene was performed in 12 and 35 selected individuals with high (S)-methadone plasma exposure and low (S)-methadone plasma exposure, respectively, from a previously described cohort of 276 patients undergoing methadone maintenance treatment. Selected genetic polymorphisms were then analyzed in the complete cohort. The rs35303484 (*11; c136A>G; M46V) polymorphism was overrepresented in the high (S)-methadone level group, whereas the rs3745274 (*9; c516G>T; Q172H), rs2279344 (c822+183G>A), and rs8192719 (c1294+53C>T) polymorphisms were underrepresented in the low (S)-methadone level group, suggesting an association with decreased CYP2B6 activity. Conversely, the rs3211371 (*5; c1459C>T; R487C) polymorphism was overrepresented in the low-level group, indicating an increased CYP2B6 activity. A higher allele frequency was found in the high-level group compared with the low-level group for rs3745274 (*9; c516G>T; Q172H), rs2279343 (*4; c785A>G; K262R) (together representing CYP2B6*6), rs8192719 (c1294+53C>T), and rs2279344 (c822+183G>A), suggesting their involvement in decreased CYP2B6 activity. These results should be replicated in larger independent cohorts. Known genetic polymorphisms in CYP2B6 contribute toward explaining extreme (S)-methadone plasma levels observed in a cohort of patients following methadone maintenance treatment.

Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

PubMed

Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

2016-08-01

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines.

PubMed

Tu, Hung-Pin; Ko, Albert Min-Shan; Wang, Shu-Jung; Lee, Chien-Hung; Lea, Rod A; Chiang, Shang-Lun; Chiang, Hung-Che; Wang, Tsu-Nai; Huang, Meng-Chuan; Ou, Tsan-Teng; Lin, Gau-Tyan; Ko, Ying-Chin

2010-02-01

Taiwanese aborigines have a high prevalence of hyperuricemia and gout. Uric acid levels and urate excretion have correlated with dopamine-induced glomerular filtration response. MAOs represent one of the major renal dopamine metabolic pathways. We aimed to identify the monoamine oxidase A (MAOA, Xp11.3) gene variants and MAO-A enzyme activity associated with gout risk. This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 x 10(-5), adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11-1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28-2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with hyperuricemia and gout (P for trend = 2.00 x 10(-3) vs. normal control). We also found that MAOA enzyme activity by rs1137070 allele was associated with hyperuricemia and gout (P for trend = 1.53 x 10(-6) vs. wild-type allele). Thus, our results show that some MAOA alleles, which have a higher enzyme activity, predispose to the development of gout.

Genetic Validation of Aminoacyl-tRNA Synthetases as Drug Targets in Trypanosoma brucei

PubMed Central

Kalidas, Savitha; Cestari, Igor; Monnerat, Severine; Li, Qiong; Regmi, Sandesh; Hasle, Nicholas; Labaied, Mehdi; Parsons, Marilyn; Stuart, Kenneth

2014-01-01

Human African trypanosomiasis (HAT) is an important public health threat in sub-Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought. Few validated enzyme targets are available to support drug discovery efforts, so our goal was to obtain essentiality data on genes with proven utility as drug targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial and fungal pathogens and are required for protein synthesis. Here we survey the essentiality of eight Trypanosoma brucei aaRSs by RNA interference (RNAi) gene expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib), arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS) (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (α and β) (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in T. brucei mammalian stage parasites showed that all were essential for parasite growth and survival in vitro. The reduced expression resulted in growth, morphological, cell cycle, and DNA content abnormalities. ThrRS was characterized in greater detail, showing that the purified recombinant enzyme displayed ThrRS activity and that the protein localized to both the cytosol and mitochondrion. Borrelidin, a known inhibitor of ThrRS, was an inhibitor of T. brucei ThrRS and showed antitrypanosomal activity. The data show that aaRSs are essential for T. brucei survival and are likely to be excellent targets for drug discovery efforts. PMID:24562907

Frequency of rs731236 (Taql), rs2228570 (Fok1) of Vitamin-D Receptor (VDR) gene in Emirati healthy population

PubMed Central

Osman, Enas; Al Anouti, Fatme; El ghazali, Gehad; Haq, Afrozul; Mirgani, Rajaa; Al Safar, Habiba

2015-01-01

Vitamin D is getting more attention everyday due to its importance in maintaining bone and calcium homeostasis, cellular proliferation, differentiation and immune response. Vitamin D is derived from diet or elicited in the skin by the activation of 7-dehydrocholesterol, which is an inert molecule that must be activated by ultraviolet light to form pre-vitamin D3. Recent studies connected the gene encoding for vitamin D (VDR) to the genetic control of bone mass and other diseases. As VDR SNPs have been associated with several disorders and diseases, it's important to investigate the allelic and genotypic distribution among populations. The aim of this study is to determine the frequency of rs731236 (Taq1) and rs2228570 (Fok1) variants in healthy Emirati individuals and compare their genotype and allele distribution with other populations. In this study 282 (female, 187; male, 95) unrelated healthy UAE nationals were involved. Two hundreds and eight two DNA samples been collected to genotype rs731236 (Taq1) and rs2228570 (Fok1) VDR SNPs. Our results indicate that the distribution of the alleles and genotypes of rs731236 (Taq1) and rs2228570 (Fok1) vary considerably in different populations. In the Emirati population the distribution of rs731236 (Taq1) and rs2228570 (Fok1) were AA 38%, AG 42%, GG 20% and AA 27%, AG 42%, GG 31% respectively. The Emirati population genotype and allele distribution of rs731236 (Taq1) and rs2228570 (Fok1) had no difference with Caucasians from USA and France. However, there was significant difference with Asian populations. PMID:26504744

Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E).

PubMed

Wu, F-Y; Liu, C-S; Liao, L-N; Li, C-I; Lin, C-H; Yang, C-W; Meng, N-H; Lin, W-Y; Chang, C-K; Hsiao, J-H; Li, T-C; Lin, C-C

2014-07-01

We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10-11.65; OR 4.74, 95 % CI 1.43-15.70; and OR 5.06, 95 % CI 1.08-23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23-23.06 and OR 5.36, 95 % CI 1.11-25.94, respectively). VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

The hURAT1 rs559946 polymorphism and the incidence of gout in Han Chinese men.

PubMed

Li, C; Yu, Q; Han, L; Wang, C; Chu, N; Liu, S

2014-01-01

Our previous study identified rs559946, a human urate transporter 1 (hURAT1) single nucleotide polymorphism (SNP), as being significantly associated with risk of primary hyperuricaemia (HUA) in a Han Chinese population. In the current study we aimed to identify the genetic effects of rs559946 on gout susceptibility in Han Chinese men. A total of 335 patients with gout and 376 healthy controls were recruited for a case-control association study. To examine the functional effect of rs559946, we performed luciferase reporter assays and an electrophoretic mobility shift assay (EMSA). rs559946 was found to be significantly associated with gout susceptibility (p = 0.004), with T-allele carriers showing a decreased risk of gout [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.89]. Multiple linear regression analysis identified a significant association between rs559946 genotypes and tophi. Luciferase reporter assays show increased transcriptional activity of the hURAT1 promoter with the C allele of rs559946. EMSA detected binding of nuclear proteins to both the T and C alleles, although increased binding was observed with the T allele. Cold competition assays suggest that rs559946 may bind within a glucocorticoid receptor (GR) binding motif. Our study suggests that the rs559946 polymorphism is associated with increased HUA risk and may also contribute to gout development in Han Chinese men. The T to C substitution within rs559946 increased the transcriptional activity, and potentially increases gout susceptibility.

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.

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.

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

PubMed Central

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

2015-01-01

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. PMID:24896148

Monoclonal Antibodies Against Tyrosyl-tRNA Synthetase and Its Isolated Cytokine-Like Domain

PubMed Central

Khoruzenko, Antonina; Cherednyk, Olga; Filonenko, Valeriy; Kornelyuk, Aleksander

2013-01-01

Tyrosyl-tRNA synthetase (TyrRS) is one of the key enzymes of protein biosynthesis. In addition to its basic role, this enzyme reveals some important non-canonical functions. Under apoptotic conditions, the full-length enzyme splits into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. The NH2-terminal catalytic fragment, known as miniTyrRS, binds strongly to the CXC-chemokine receptor CXCR1 and, like interleukin 8, functions as a chemoattractant for polymorphonuclear leukocytes. On the other hand, an extra COOH-terminal domain of human TyrRS has cytokine activities like those of a mature human endothelial monocyte-activating polypeptide II (EMAP II). Moreover, the etiology of specific diseases (cancer, neuronal pathologies, autoimmune disorders, and disrupted metabolic conditions) is connected to specific aminoacyl-tRNA synthetases. Here we report the generation and characterization of monoclonal antibodies specific to N- and C-terminal domains of TyrRS. Recombinant TyrRS and its N- and C-terminal domains were expressed as His-tag fusion proteins in bacteria. Affinity purified proteins have been used as antigens for immunization and hybridoma cell screening. Monoclonal antibodies specific to catalytic N-terminal module and C-terminal EMAP II-like domain of TyrRS may be useful as tools in various aspects of TyrRS function and cellular localization. PMID:23750478

Polymorphisms in inflammasome genes and risk of asthma in Brazilian children.

PubMed

Leal, Vinicius Nunes Cordeiro; Genov, Isabel Rugue; Mallozi, Márcia C; Solé, Dirceu; Pontillo, Alessandra

2018-01-01

Considering its role in inflammation and recently described "alternative" roles in epithelial homeostasis and Th1/Th2 balance, we hypothesize that inflammasome genetics could contribute to the development of asthma. Selected functional polymorphisms in inflammasome genes are evaluated in a cohort of asthmatic children and their families. Gain-of-function NLRP1 variants rs11651270, rs12150220 and rs2670660 resulted significantly associated to asthma in trios (TDT) analysis; and rs11651270 and rs2670660 also with asthma severity and total IgE level in asthmatic children. NLRP1 activators in humans are still unknown, however we hypothesized that individuals with gain-of-function SNPs in NLRP1 could be more prone in activating inflammasome in the presence of asthma-related cell stressors (i.e. ER stress or ROS), and this activation contribute to exacerbate inflammatory response and asthma development. Gain-of-function IL1A rs17561 resulted significantly associated with a reduced pulmonary capacity in asthmatic children. IL18 rs5744256 which lead to lower serum level of IL-18 appeared to be associated to a worse response to bronchodilators. Concluding, this work provides evidences about the contribution of inflammasome genetics in the development of paediatric asthma, both considering its inflammatory role in alveolar macrophages (i.e.: NLRP1) or its homeostatic role in lung epithelial cells (i.e.: IL1A, IL18). Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of the calcium release channel from rabbit skeletal muscle by the nucleotides ATP, AMP, IMP and adenosine

PubMed Central

Laver, Derek R; Lenz, Gerlinde K E; Lamb, Graham D

2001-01-01

Nucleotide activation of skeletal muscle ryanodine receptors (RyRs) was studied in planar lipid bilayers in order to understand RyR regulation in vivo under normal and fatigued conditions. With ‘resting’ calcium (100 nm cytoplasmic and 1 mm luminal), RyRs had an open probability (Po) of ∼0.01 in the absence of nucleotides and magnesium. ATP reversibly activated RyRs with Po at saturation (Pmax) ∼0.33 and Ka (concentration for half-maximal activation) ∼0.36 mm and with a Hill coefficient (nH) of ∼1.8 in RyRs when Pmax < 0.5 and ∼4 when Pmax > 0.5. AMP was a much weaker agonist (Pmax∼0.09) and adenosine was weaker still (Pmax∼0.01–0.02), whereas inosine monophosphate (IMP), the normal metabolic end product of ATP hydrolysis, produced no activation at all. Adenosine acted as a competitive antagonist that reversibly inhibited ATP- and AMP-activated RyRs with nH∼1 and Ki∼0.06 mm at [ATP] < 0.5 mm, increasing 4-fold for each 2-fold increase in [ATP] above 0.5 mm. This is explained by the binding of a single adenosine preventing the cooperative binding of two ATP or AMP molecules, with dissociation constants of 0.4, 0.45 and 0.06 mm for ATP, AMP and adenosine, respectively. Importantly, IMP (≤ 8 mm) had no inhibitory effect whatsoever on ATP-activated RyRs. Mean open (τo) and closed (τc) dwell-times were more closely related to Po than to the nucleotide species or individual RyRs. At Po < 0.2, RyR regulation occurred via changes in τc, whereas at higher Po this also occurred via changes in τo. The detailed properties of activation and competitive inhibition indicated complex channel behaviour that could be explained in terms of a model involving interactions between different subunits of the RyR homotetramer. The results also show how deleterious adenosine accumulation is to the function of RyRs in skeletal muscle and, by comparison with voltage sensor-controlled Ca2+ release, indicate that voltage sensor activation requires ATP binding to the RyR to be effective. PMID:11744753

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

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

PubMed

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.

A novel role for GSK3β as a modulator of Drosha microprocessor activity and MicroRNA biogenesis.

PubMed

Fletcher, Claire E; Godfrey, Jack D; Shibakawa, Akifumi; Bushell, Martin; Bevan, Charlotte L

2016-10-23

Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA. Indeed, GSK3β itself can immunoprecipitate pri-miRs, suggesting possible RNA-binding capacity. Kinase assays identify the mechanism for GSK3β-enhanced Drosha activity, which requires GSK3β nuclear localisation, as phosphorylation of Drosha at S 300 and/or S 302 ; confirmed by enhanced Drosha activity and association with cofactors, and increased abundance of mature miRs in the presence of phospho-mimic Drosha. Functional implications of GSK3β-enhanced miR biogenesis are illustrated by increased levels of GSK3β-upregulated miR targets following GSK3β inhibition. These data, the first to link GSK3β with the miR cascade in humans, highlight a novel pro-biogenesis role for GSK3β in increasing miR biogenesis as a component of the Microprocessor complex with wide-ranging functional consequences. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.

PubMed

Fischer, Viktoria; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

2014-06-01

The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal networks. © 2014 International Society for Neurochemistry.

A p-coumaroyl esterase from Rhizoctonia solani with a pronounced chlorogenic acid esterase activity.

PubMed

Nieter, Annabel; Kelle, Sebastian; Linke, Diana; Berger, Ralf G

2017-07-25

Extracellular esterase activity was detected in submerged cultures of Rhizoctonia solani grown in the presence of sugar beet pectin or Tween 80. Putative type B feruloyl esterase (FAE) coding sequences found in the genome data of the basidiomycete were heterologously expressed in Pichia pastoris. Recombinant enzyme production on the 5-L bioreactor scale (Rs pCAE: 3245UL -1 ) exceeded the productivity of the wild type strain by a factor of 800. Based on substrate specificity profiling, the purified recombinant Rs pCAE was classified as a p-coumaroyl esterase (pCAE) with a pronounced chlorogenic acid esterase side activity. The Rs pCAE was also active on methyl cinnamate, caffeate and ferulate and on feruloylated saccharides. The unprecedented substrate profile of Rs pCAE together with the lack of sequence similarity to known FAEs or pCAEs suggested that the Rs pCAE represents a new type of enzyme. Hydroxycinnamic acids were released from agro-industrial side-streams, such as destarched wheat bran (DSWB), sugar beet pectin (SBP) and coffee pulp (CP). Overnight incubation of coffee pulp with the Rs pCAE resulted in the efficient release of p-coumaric (100%), caffeic (100%) and ferulic acid (85%) indicating possible applications for the valorization of food processing wastes and for the enhanced degradation of lignified biomass. Copyright © 2017 Elsevier B.V. All rights reserved.

Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

PubMed

Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

2015-07-01

Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

... shall be limited to a maximum of 2.0% active ingredient. Contamination of food or food contact surfaces... 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...

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

PubMed

Goldsmith, Felicia; Guice, Justin; Page, Ryan; Welsh, David A; Taylor, Christopher M; Blanchard, Eugene E; Luo, Meng; Raggio, Anne M; Stout, Rhett W; Carvajal-Aldaz, Diana; Gaither, Amanda; Pelkman, Christine; Ye, Jianping; Martin, Roy J; Geaghan, James; Durham, Holiday A; Coulon, Diana; Keenan, Michael J

2017-01-01

To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.

PubMed

Kinoshita, Akihide; Takizawa, Ryu; Koike, Shinsuke; Satomura, Yoshihiro; Kawasaki, Shingo; Kawakubo, Yuki; Marumo, Kohei; Tochigi, Mamoru; Sasaki, Tsukasa; Nishimura, Yukika; Kasai, Kiyoto

2015-10-01

The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration.

PubMed

Ceci, Marcello; Carlantoni, Claudia; Missinato, Maria Azzurra; Bonvissuto, Davide; Di Giacomo, Bruna; Contu, Riccardo; Romano, Nicla

2018-01-01

Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified. In this work, in order to investigate if the downregulation of these miRNAs (miRs) are linked with the activation of epicardium, the expressions of miR-133a, b and miR-1 during regeneration were analysed. qPCR analyses in whole-heart, or from distinct dissected epicardial cells comparing to regenerative clot (containing cardiomyocytes, fibroblasts and endocardial cells) by a laser-micro-dissector, have indicated that already at 24 h there is a downregulation of miRs: (1) miR-133a and miR-1 in the epicardium and (2) miR-133b and miR-1 in the regenerative clot. All the miRs remain downregulated until 7 days post-surgery. With the aim to visualize the activations of heart component in combination with miRs, we developed immunohistochemistry using antibodies directed against common markers in mammals as well as zebrafish: Wilms tumour 1 (WT1), a marker of epicardium; heat-shock protein 70 (HSP70), a chaperon activated during regeneration; and the Cardiac Troponin T (cTnT), a marker of differentiated cardiomyocytes. All these markers are directly or indirectly linked to the investigated miRs. WT1 and HSP70 strongly marked the regeneration site just at 2-3 days postventricular resection. In coherence, cTnT intensively marked the regenerative portion from 7 days onwards. miRs-1 and -133 (a,b) have been strongly involved in the activation of epicardium and regenerative clot during the regeneration process in zebrafish. This study can be a useful translational model to understand the early epicardial activation in which miRs-133a and miR-1 seem to play a central role as observed in the human heart.

Annual Meeting of the Academy of Sciences USSR. 24-26 February 1960

DTIC Science & Technology

1960-08-29

tarth’s crust to the mantle. If we cvn imagine what this work will gJive us, then the use of the term " colossal " is not an oxaýgerationa, 222. It must bo...recently we have seen with our own eyes the wide introduction of semiconductor devices. Semiconductors have permitte •. the solution of a number of important

A resolution congratulating the Navy and the current and former officers and crew of the U.S.S. Enterprise (CVN 65) on completion of the 26th and final deployment of the vessel.

THOMAS, 112th Congress

Sen. Warner, Mark R. [D-VA

2013-01-02

Senate - 01/02/2013 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

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

DTIC Science & Technology

2013-08-08

of $141 million and a decline in disposable income of $349 million.), and $10 million more in local tax contributions ( the ...Department of Defense are considered; the consideration given in the decision-making process to shortfalls in other service budgets and other internal ...strategic plan of the Navy for the manner in which the Littoral Combat Ship (LCS) will fulfill the roles

Marine Structural Steel Toughness Data Bank. Volume 4

DTIC Science & Technology

1990-08-31

Break? Did specimen fracture completely? CODIc Critical COD CODi Initial COD CVN Energy Charpy V Energy Crack lgth Crack Length Curve Curve Shape DT...Onien Test Temp COIi CODIc i1 imax Tear Mod degF in In in-lb/in**2 in-lb/in**2 in-lb/in**2 L-T 72 0.0236 0.0380 4346 4315 260.2 L-T 72

Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling.

PubMed

Freund, Jenna R; Mansfield, Corrine J; Doghramji, Laurel J; Adappa, Nithin D; Palmer, James N; Kennedy, David W; Reed, Danielle R; Jiang, Peihua; Lee, Robert J

2018-05-10

Bitter taste receptors (T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We showed previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2Rs 4, 14, 16, and 38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens. Bacterial quorum-sensing acyl-homoserine lactones (AHLs) activate T2Rs and stimulate these responses in primary airway cells.  Quinolones are another type of quorum sensing molecule used by Pseudomonas aeruginosa.  To elucidate if bacterial quinolones activate airway T2Rs, we analyzed calcium, cAMP, and NO dynamics using a combination of fluorescent indicator dyes and FRET-based protein biosensors.  T2R-transfected HEK293T cells, several lung epithelial cell lines, and primary sinonasal cells grown and differentiated at air-liquid interface were tested with 2-heptyl-3-hydroxy-4-quinolone (known as Pseudomonas quinolone signal; PQS), 2,4-dihydroxyquinolone (DHQ), and 4-hydroxy-2-heptylquinolone (HHQ). In HEK293T cells, PQS activated T2R4, 16, and 38 while HHQ activated T2R14.  DHQ had no effect.  PQS and HHQ increased calcium and decreased both baseline and stimulated cAMP levels in cultured and primary airway cells.  In primary cells, PQS and HHQ activated levels of NO synthesis previously shown to be bactericidal. This study suggests airway T2R-mediated immune responses are activated by bacterial quinolones as well as AHLs. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

The interacting binary white dwarf systems

NASA Astrophysics Data System (ADS)

Provencal, Judith Lucille

1994-01-01

Interacting binary white dwarfs are believed to contain two white dwarfs of extreme mass ratio, one of which is filling its Roche Lobe, transferring material to its companion via an accretion disk. The defining characteristic of an IBWD is the nondetection of hydrogen in the system. IBWD's represent the culmination of binary star evolution. In this final death dance, two degenerate objects are entangled, the massive white dwarf tidally stripping and devouring its helpless companion's outer layers. Because a white dwarf expands as it loses mass, the end result of this process is the complete absorption of one star by the other . My goal in the examination of these systems is to understand their photometric behavior and determine the best model of these objects. The IBWD's represent the endpoint of binary evolution. Knowledge of the physical properties of these objects will provide constraints on theories of binary evolution, white dwarf formation, the thermal and physical structure of accreting white dwarfs, and nucleosynthesis. To achieve this goal, I have analyzed the most comprehensive high speed photometric data sets available on 5 of the 6 known objects: AM CVn, PG1346+082, CP Eri, V803 Cen, and G61-29. AM CVn and PG1346+0S2 were targets of the Whole Earth Telescope in 1988 and 1990 respectively. We find a range of variation timescales, from minutes to days, and a range of physical behaviour. Most importantly, we measure a rate of period change of P = 1.68 +/- 0.03 x 10-11s/s for the dominant variation in AM CVn. We also find the differences in behavior can be attributed to a difference in mass transfer rate that may be evolutionary in origin. Finally, I discuss in detail the observational characteristics of each object, and overall properties of the IBWD family. In conclusion, I discuss past and future history of these objects, and touch on their possible influence on our knowledge of white dwarf evolution and formation. The IBWD's are possible progenitors of helium white dwarfs. If this hypothesis is correct, these systems represent a second entry point onto the white dwarf cooling curve.

Accuracy of various human NAT2 SNP genotyping panels to infer rapid, intermediate and slow acetylator phenotypes

PubMed Central

Hein, David W; Doll, Mark A

2012-01-01

Aim Humans exhibit genetic polymorphism in NAT2 resulting in rapid, intermediate and slow acetylator phenotypes. Over 65 NAT2 variants possessing one or more SNPs in the 870-bp NAT2 coding region have been reported. The seven most frequent SNPs are rs1801279 (191G>A), rs1041983 (282C>T), rs1801280 (341T>C), rs1799929 (481C>T), rs1799930 (590G>A), rs1208 (803A>G) and rs1799931 (857G>A). The majority of studies investigate the NAT2 genotype assay for three SNPs: 481C>T, 590G>A and 857G>A. A tag-SNP (rs1495741) recently identified in a genome-wide association study has also been proposed as a biomarker for the NAT2 phenotype. Materials & methods Sulfamethazine N-acetyltransferase catalytic activities were measured in cryopreserved human hepatocytes from a convenience sample of individuals in the USA with an ethnic frequency similar to the 2010 US population census. These activities were segregated by the tag-SNP rs1495741 and each of the seven SNPs described above. We assessed the accuracy of the tag-SNP and various two-, three-, four- and seven-SNP genotyping panels for their ability to accurately infer NAT2 phenotype. Results The accuracy of the various NAT2 SNP genotype panels to infer NAT2 phenotype were as follows: seven-SNP: 98.4%; tag-SNP: 77.7%; two-SNP: 96.1%; three-SNP: 92.2%; and four-SNP: 98.4%. Conclusion A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non-European ancestry. PMID:22092036

Synergistic control of protein kinase Cgamma activity by ionotropic and metabotropic glutamate receptor inputs in hippocampal neurons.

PubMed

Codazzi, Franca; Di Cesare, Alessandra; Chiulli, Nino; Albanese, Alberto; Meyer, Tobias; Zacchetti, Daniele; Grohovaz, Fabio

2006-03-29

Conventional protein kinase C (PKC) isoforms are abundant neuronal signaling proteins with important roles in regulating synaptic plasticity and other neuronal processes. Here, we investigate the role of ionotropic and metabotropic glutamate receptor (iGluR and mGluR, respectively) activation on the generation of Ca2+ and diacylglycerol (DAG) signals and the subsequent activation of the neuron-specific PKCgamma isoform in hippocampal neurons. By combining Ca2+ imaging with total internal reflection microscopy analysis of specific biosensors, we show that elevation of both Ca2+ and DAG is necessary for sustained translocation and activation of EGFP (enhanced green fluorescent protein)-PKCgamma. Both DAG production and PKCgamma translocation were localized processes, typically observed within discrete microdomains along the dendritic branches. Markedly, intermediate-strength NMDA receptor (NMDAR) activation or moderate electrical stimulation generated Ca2+ but no DAG signals, whereas mGluR activation generated DAG but no Ca2+ signals. Both receptors were needed for PKCgamma activation. This suggests that a coincidence detection process exists between iGluRs and mGluRs that relies on a molecular coincidence detection process based on the corequirement of Ca2+ and DAG for PKCgamma activation. Nevertheless, the requirement for costimulation with mGluRs could be overcome for maximal NMDAR stimulation through a direct production of DAG via activation of the Ca2+-sensitive PLCdelta (phospholipase Cdelta) isoform. In a second important exception, mGluRs were sufficient for PKCgamma activation in neurons in which Ca2+ stores were loaded by previous electrical activity. Together, the dual activation requirement for PKCgamma provides a plausible molecular interpretation for different synergistic contributions of mGluRs to long-term potentiation and other synaptic plasticity processes.

Non-Synonymous Single-Nucleotide Polymorphisms and Physical Activity Interactions on Adiposity Parameters in Malaysian Adolescents.

PubMed

Zaharan, Nur Lisa; Muhamad, Nor Hanisah; Jalaludin, Muhammad Yazid; Su, Tin Tin; Mohamed, Zahurin; Mohamed, M N A; A Majid, Hazreen

2018-01-01

Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia. We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study ( n  = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model. PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p  = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p  = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p  = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p  = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p  = 0.01) for % BF. Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

Spontaneous brain activity predicts learning ability of foreign sounds.

PubMed

Ventura-Campos, Noelia; Sanjuán, Ana; González, Julio; Palomar-García, María-Ángeles; Rodríguez-Pujadas, Aina; Sebastián-Gallés, Núria; Deco, Gustavo; Ávila, César

2013-05-29

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.

Routines, roles, and responsibilities for aligning scientific and classroom practices

NASA Astrophysics Data System (ADS)

Ford, Michael J.; Wargo, Brian M.

2007-01-01

Reform efforts in science education have focused on engaging students in authentic scientific practices. For these efforts to succeed, detailed articulations of scientific practice need to be linked to understandings of classroom practice. Here we characterize engagement in practice generally in terms of 3Rs: routines, roles, and responsibilities. We argue that there is a misalignment between the 3Rs of scientific practice and the practices common in classrooms, and that this misalignment poses a considerable obstacle for beginning teachers who attempt to implement reform pedagogy. As part of a secondary methods course, 16 preservice teachers (PSTs) participated in two exemplar activities designed to engage them in scientific practices. The PST performances suggest that at least initially, they did not consider authentic scientific practices appropriate for classroom activities, implying a pedagogical repertoire dominated by the 3Rs of traditional classrooms. PST performances, however, evidenced a shift in the 3Rs from those common in classrooms to those required by these activities, suggesting that their visions for classrooms are malleable and underlining the importance of aligning the 3Rs of scientific and classroom practices during teacher preparation.

The role of resting-state EEG localized activation and central nervous system arousal in executive function performance in children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Zhang, Da-Wei; Johnstone, Stuart J; Roodenrys, Steven; Luo, Xiangsheng; Li, Hui; Wang, Encong; Zhao, Qihua; Song, Yan; Liu, Lu; Qian, Qiujin; Wang, Yufeng; Sun, Li

2018-06-01

This study explored the relationships between resting-state electroencephalogram (RS-EEG) localized activation and two important types of executive functions (EF) to extend the prognostic utilization of RS-EEG in children with Attention-Deficit/Hyperactivity Disorder (AD/HD). Also, the role of central nervous system (CNS) arousal in the relationships was examined. Fifty-eight children with AD/HD participated in the study. RS-EEG localized activation was derived from spectral power differences between EEG in eyes-closed and eyes-open conditions. CNS arousal was measured based on alpha band power. Common and everyday EF scores were obtained as EF outcomes. Frontal delta activation predicted common EF ability and posterior alpha activation predicted everyday EF. A serial mediation analysis found that lower CNS baseline arousal was related to greater arousal and delta activation in series, which in turn related to worse common EF. A follow-up study found that baseline arousal was related to larger interference cost. RS-EEG is indicative of individual differences in two important types of EF in children with AD/HD. Lower CNS arousal may be a driving force for the poorer common EF performance. The current study supports prognostic utilization of RS-EEG and AD/HD models that take resting brain activity into consideration in children with AD/HD. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Invited Talk: Photometry of Bright Variable Stars with the BRITE Constellation Nano-Satellites: Opportunities for Amateur Astronomers

NASA Astrophysics Data System (ADS)

Guinan, E. F.

2014-06-01

(Abstract only) The BRIght Target Explorer (BRITE) is a joint Austrian-Canadian-Polish Astronomy mission to carry out high precision photometry of bright (mv < 4 mag.) variable stars. BRITE consists of a "Constellation" of 20 × 20 × 20-cm nano-satellite cubes equipped with wide field (20 × 24 deg.) CCD cameras, control systems, solar panels, onboard computers, and so on. The first two (of up to six) satellites were successfully launched during February 2013. After post-launch commissioning, science operations commenced during October 2013. The primary goals are to carry out continuous multi-color (currently blue and red filters) high-precision millimag (mmag) photometry in particular locations in the sky. Typically these pointings will last for two to four months and secure simultaneous blue/red photometry of bright variable stars within the field. The first science pointing is centered on the Orion region. Since most bright stars are intrinsically luminous, hot O/B stars, giants, and supergiants will be the most common targets. However, some bright eclipsing binaries (such as Algol, b Lyr, e Aur) and a few chromospherically-active RS CVn stars (such as Capella) may be eventually be monitored. The BRITE-Constellation program of high precision, two color photometry of bright stars offers a great opportunity to study a wide range of stellar astrophysical problems. Bright stars offer convenient laboratories to study many current and important problems in stellar astrophysics. These include probing stellar interiors and pulsation in pulsating stars, tests of stellar evolution and structure for Cepheids and other luminous stars. To scientifically enhance the BRITE science returns, the BRITE investigators are very interested in securing contemporaneous ground-based spectroscopy and standardized photometry of target stars. The BRITE Ground Based Observations Team is coordinating ground-based observing efforts for BRITE targets. The team helps coordinate collaborations with amateur and professional astronomer. The ground-based coordinators are: Thomas Eversberg (thomas.eversberg@dlr.de) and, for spectroscopy, Contanze Zwintz (konstanze@ster.kuleuven.be). Detailed information about the BRITE Mission is provided at: www.brite-contellation.at.

A novel Nrf2 activator from microbial transformation inhibits radiation-induced dermatitis in mice

PubMed Central

Nakagami, Yasuhiro; Masuda, Kayoko

2016-01-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that regulates many antioxidants, and we have recently succeeded in obtaining a novel Nrf2 activator, RS9, from microbial transformation. RS9 is categorized as a triterpenoid, and well-known triterpenoids such as RTA 402 (bardoxolone methyl) and RTA 408 have been tested in clinical trials. RTA 408 lotion is currently being tested in patients at risk for radiation dermatitis. This prompted us to study the profiles of RS9 in the skin. All the above triterpenoids increased the level of an Nrf2-targeted gene, NADPH:quinone oxidoreductase-1, in normal human epidermal keratinocytes. Among them, the activity of RS9 was prominent; furthermore, the cellular toxicity was less compared with RTA compounds. BALB/c mice were irradiated with 30 Gy/day on Day 0, and compounds were topically applied on the back once daily from Day 1 to Day 30. Dermatitis scores peaked on Day 18, with a score of 2.6 in vehicle-treated mice, and topical applications of 0.1% RTA 402, RTA 408 and RS9 reduced the scores to 1.8, 2.0 and 1.4, respectively. Moreover, the percentage of animals with scores ≥2 was analyzed, and 0.1% RS9 suppressed the percentage from 100% to 47%. These results imply that RS9 has potential efficacy for treating radiation dermatitis. PMID:27242339

Functional Consequences of a Novel Variant of PCSK1

PubMed Central

Pickett, Lindsay A.; Yourshaw, Michael; Albornoz, Valeria; Chen, Zijun; Solorzano-Vargas, R. Sergio; Nelson, Stanley F.; Martín, Martín G.; Lindberg, Iris

2013-01-01

Background Common single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity. Methodology/Principal Findings A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3. Conclusion/Significance Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted. PMID:23383060

Functional consequences of a novel variant of PCSK1.

PubMed

Pickett, Lindsay A; Yourshaw, Michael; Albornoz, Valeria; Chen, Zijun; Solorzano-Vargas, R Sergio; Nelson, Stanley F; Martín, Martín G; Lindberg, Iris

2013-01-01

Common single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity. A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3. Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted.

Analogs of methyllycaconitine as novel noncompetitive inhibitors of nicotinic receptors: pharmacological characterization, computational modeling, and pharmacophore development.

PubMed

McKay, Dennis B; Chang, Cheng; González-Cestari, Tatiana F; McKay, Susan B; El-Hajj, Raed A; Bryant, Darrell L; Zhu, Michael X; Swaan, Peter W; Arason, Kristjan M; Pulipaka, Aravinda B; Orac, Crina M; Bergmeier, Stephen C

2007-05-01

As a novel approach to drug discovery involving neuronal nicotinic acetylcholine receptors (nAChRs), our laboratory targeted nonagonist binding sites (i.e., noncompetitive binding sites, negative allosteric binding sites) located on nAChRs. Cultured bovine adrenal cells were used as neuronal models to investigate interactions of 67 analogs of methyllycaconitine (MLA) on native alpha3beta4* nAChRs. The availability of large numbers of structurally related molecules presents a unique opportunity for the development of pharmacophore models for noncompetitive binding sites. Our MLA analogs inhibited nicotine-mediated functional activation of both native and recombinant alpha3beta4* nAChRs with a wide range of IC(50) values (0.9-115 microM). These analogs had little or no inhibitory effects on agonist binding to native or recombinant nAChRs, supporting noncompetitive inhibitory activity. Based on these data, two highly predictive 3D quantitative structure-activity relationship (comparative molecular field analysis and comparative molecular similarity index analysis) models were generated. These computational models were successfully validated and provided insights into the molecular interactions of MLA analogs with nAChRs. In addition, a pharmacophore model was constructed to analyze and visualize the binding requirements to the analog binding site. The pharmacophore model was subsequently applied to search structurally diverse molecular databases to prospectively identify novel inhibitors. The rapid identification of eight molecules from database mining and our successful demonstration of in vitro inhibitory activity support the utility of these computational models as novel tools for the efficient retrieval of inhibitors. These results demonstrate the effectiveness of computational modeling and pharmacophore development, which may lead to the identification of new therapeutic drugs that target novel sites on nAChRs.

Small cysteine-rich antifungal proteins from radish: their role in host defense.

PubMed Central

Terras, F R; Eggermont, K; Kovaleva, V; Raikhel, N V; Osborn, R W; Kester, A; Rees, S B; Torrekens, S; Van Leuven, F; Vanderleyden, J

1995-01-01

Radish seeds have previously been shown to contain two homologous, 5-kD cysteine-rich proteins designated Raphanus sativus-antifungal protein 1 (Rs-AFP1) and Rs-AFP2, both of which exhibit potent antifungal activity in vitro. We now demonstrate that these proteins are located in the cell wall and occur predominantly in the outer cell layers lining different seed organs. Moreover, Rs-AFPs are preferentially released during seed germination after disruption of the seed coat. The amount of released proteins is sufficient to create a microenvironment around the seed in which fungal growth is suppressed. Both the cDNAs and the intron-containing genomic regions encoding the Rs-AFP preproteins were cloned. Transcripts (0.55 kb) hybridizing with an Rs-AFP1 cDNA-derived probe were present in near-mature and mature seeds. Such transcripts as well as the corresponding proteins were barely detectable in healthy uninfected leaves but accumulated systemically at high levels after localized fungal infection. The induced leaf proteins (designated Rs-AFP3 and Rs-AFP4) were purified and shown to be homologous to seed Rs-AFPs and to exert similar antifungal activity in vitro. A chimeric Rs-AFP2 gene under the control of the constitutive cauliflower mosaic virus 35S promoter conferred enhanced resistance to the foliar pathogen Alternaria longipes in transgenic tobacco. The term "plant defensins" is proposed to denote these defense-related proteins. PMID:7780308

The X-linked juvenile retinoschisis protein retinoschisin is a novel regulator of mitogen-activated protein kinase signalling and apoptosis in the retina.

PubMed

Plössl, Karolina; Weber, Bernhard H F; Friedrich, Ulrike

2017-04-01

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy in young males, caused by mutations in the RS1 gene. The function of the encoded protein, termed retinoschisin, and the molecular mechanisms underlying XLRS pathogenesis are still unresolved, although a direct interaction partner of the secreted retinoschisin, the retinal Na/K-ATPase, was recently identified. Earlier gene expression studies in retinoschisin-deficient (Rs1h -/Y ) mice provided a first indication of pathological up-regulation of mitogen-activated protein (MAP) kinase signalling in disease pathogenesis. To further investigate the role for retinoschisin in MAP kinase regulation, we exposed Y-79 cells and murine Rs1h -/Y retinae to recombinant retinoschisin and the XLRS-associated mutant RS1-C59S. Although normal retinoschisin stably bound to retinal cells, RS1-C59S exhibited a strongly reduced binding affinity. Simultaneously, exposure to normal retinoschisin significantly reduced phosphorylation of C-RAF and MAP kinases ERK1/2 in Y-79 cells and murine Rs1h -/Y retinae. Expression of MAP kinase target genes C-FOS and EGR1 was also down-regulated in both model systems. Finally, retinoschisin treatment decreased pro-apoptotic BAX-2 transcript levels in Y-79 cells and Rs1h -/Y retinae. Upon retinoschisin treatment, these cells showed increased resistance against apoptosis, reflected by decreased caspase-3 activity (in Y-79 cells) and increased photoreceptor survival (in Rs1h -/Y retinal explants). RS1-C59S did not influence C-RAF or ERK1/2 activation, C-FOS or EGR1 expression, or apoptosis. Our data imply that retinoschisin is a novel regulator of MAP kinase signalling and exerts an anti-apoptotic effect on retinal cells. We therefore discuss that disturbances of MAP kinase signalling by retinoschisin deficiency could be an initial step in XLRS pathogenesis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A Functional Variant rs6435156C > T in BMPR2 is Associated With Increased Risk of Chronic Obstructive Pulmonary Disease (COPD) in Southern Chinese Population.

PubMed

Wang, Jian; Zhang, Chenting; Zhang, Zili; Zheng, Zeguang; Sun, Dejun; Yang, Quan; Hadadi, Cyrus; Li, Defu; Xu, Xiaoming; Xiong, Mingmei; Zhou, Qipeng; Guo, Meihua; Wang, Yingfeng; Tang, Chun; Xu, Guihua; Yang, Kai; Zhong, Nanshan; Lu, Wenju

2016-03-01

Bone morphogenetic protein receptor type 2 (BMPR2) signaling is anti-inflammatory. Decreased BMPR2 expression was seen in lung tissue from chronic obstructive pulmonary disease (COPD) patients. The selected single nucleotide polymorphisms (SNPs) in BMPR2 were genotyped with polymerase chain reaction (PCR) ligase detection reaction. The effects of SNPs on gene expression were analyzed with luciferase assays. The mRNA and protein expression levels of BMPR2 in peripheral blood mononuclear cells (PBMCs) from COPD patients were determined by quantitative PCR and western blotting, respectively. Two SNPs, rs6435156C > T and rs1048829G > T in the 3'-untranslated region (3'UTR) of BMPR2 were selected and genotyped in COPD case and healthy control subjects from southern Chinese population. Both of them were found associated with significantly increased COPD risk (adjusted odds ratio [OR] = 1.58 with 95% confidence interval [CI] = 1.14-2.15, P = 0.0056 for rs6435156C > T; adjusted OR = 1.47 and 95% CI = 1.10-1.97, P = 0.0092 for rs1048829G > T). Older age, cigarette smoking, family history of cancer and COPD were all factors that interacted with rs6435156C > T and rs1048829G > T causing increased COPD risk. Cigarette smokers with rs6435156 (CT + TT) or rs1048829 (GT + TT) were more susceptible to COPD than that with the rs6435156CC or rs1048829GG genotypes. In A549 human alveolar epithelial cells, luciferase reporter assays revealed that introduction of 3'UTR of BMPR2 plasmids carrying rs6435156T allele but not rs1048829T led to lower luciferase activity than the wild-type C or G alleles. Comparing to rs6435156CC, treatment with hsa-miR-20a mimics deceased whereas hsa-miR-20a inhibitor restored the luciferase reporter activity in cells transfected with constructs carrying rs6435156TT. BMPR2 mRNA and protein expressions were significantly lower in PBMCs from COPD smokers than that in non-smokers. COPD patients carrying rs6435156T allele had less BMPR2 expression in PBMCs. This study demonstrated that both rs6435156C > T and rs1048829G > T variants in BMPR2 contributed to increased susceptibility to COPD. The T variants of rs6435156 increased COPD risk likely by binding with hsa-miR-20a, thus leading to downregulated BMPR2 expression in lung epithelial and immune cells.

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

PubMed Central

Benthall, Katelyn N.; Hough, Ryan A.

2016-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. PMID:27760818

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

PubMed

Benthall, Katelyn N; Hough, Ryan A; McClellan, Andrew D

2017-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. Copyright © 2017 the American Physiological Society.

Preferential Binding to Elk-1 by SLE-Associated IL10 Risk Allele Upregulates IL10 Expression

PubMed Central

Kelly, Jennifer A.; Brown, Elizabeth E.; Harley, John B.; Bae, Sang-Cheol; Alarcόn-Riquelme, Marta E.; Edberg, Jeffrey C.; Kimberly, Robert P.; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Alarcón, Graciela S.; Kaufman, Kenneth M.; Vyse, Timothy J.; Jacob, Chaim O.; Gaffney, Patrick M.; Sivils, Kathy Moser; James, Judith A.; Kamen, Diane L.; Gilkeson, Gary S.; Niewold, Timothy B.; Merrill, Joan T.; Scofield, R. Hal; Criswell, Lindsey A.; Stevens, Anne M.; Boackle, Susan A.; Kim, Jae-Hoon; Choi, Jiyoung; Pons-Estel, Bernardo A.; Freedman, Barry I.; Anaya, Juan-Manuel; Martin, Javier; Yu, C. Yung; Chang, Deh-Ming; Song, Yeong Wook; Langefeld, Carl D.; Chen, Weiling; Grossman, Jennifer M.; Cantor, Rita M.; Hahn, Bevra H.; Tsao, Betty P.

2013-01-01

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans. PMID:24130510

Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

PubMed

Sakurai, Daisuke; Zhao, Jian; Deng, Yun; Kelly, Jennifer A; Brown, Elizabeth E; Harley, John B; Bae, Sang-Cheol; Alarcόn-Riquelme, Marta E; Edberg, Jeffrey C; Kimberly, Robert P; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S; Kaufman, Kenneth M; Vyse, Timothy J; Jacob, Chaim O; Gaffney, Patrick M; Sivils, Kathy Moser; James, Judith A; Kamen, Diane L; Gilkeson, Gary S; Niewold, Timothy B; Merrill, Joan T; Scofield, R Hal; Criswell, Lindsey A; Stevens, Anne M; Boackle, Susan A; Kim, Jae-Hoon; Choi, Jiyoung; Pons-Estel, Bernardo A; Freedman, Barry I; Anaya, Juan-Manuel; Martin, Javier; Yu, C Yung; Chang, Deh-Ming; Song, Yeong Wook; Langefeld, Carl D; Chen, Weiling; Grossman, Jennifer M; Cantor, Rita M; Hahn, Bevra H; Tsao, Betty P

2013-01-01

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10⁻⁸, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

Effects of rs6234/rs6235 and rs6232/rs6234/rs6235 PCSK1 single-nucleotide polymorphism clusters on proprotein convertase 1/3 biosynthesis and activity.

PubMed

Mbikay, Majambu; Sirois, Francine; Nkongolo, Kabwe K; Basak, Ajoy; Chrétien, Michel

2011-12-01

Proprotein convertase 1/3 (PC1/3) is one of the endoproteases initiating the proteolytic activation of prohormones and proneuropeptides in the secretory pathway. It is produced as a zymogen that is subsequently modified by activity-determining cleavages at the amino and the carboxyl termini. In human, it is encoded by the PCSK1 locus on chromosome 5. Spontaneous inactivating mutations in its gene have been linked to obesity. Minor alleles of the common non-synonymous single-nucleotide polymorphisms (SNPs) rs6232 (T>C, N221D), rs6234 (G>C, Q665E) and rs6235 (C>G, S690T) have been associated with increased risk of obesity. We have shown that the variations associated with these SNPs are linked on minor PCSK1 alleles. In this study, we examined the impact of amino acid substitutions specified by the minor PCSK1 alleles on PC1/3 biosynthesis and prohormone processing activity in cultured cells. The common and variant isoforms of PC1/3 were expressed in transfected rat pituitary GH4C1 cells with or without proopiomelanocortin (POMC) as a substrate. Secreted PC1/3- or POMC-related proteins and peptides were analyzed by immunoblotting and immunoprecipitation. When expressed in GH4C1 cells, the triple-variant PC1/3 underwent significantly more proteolytic processing at the amino and carboxyl termini than the common and double-variant isoforms. However, there was no detectable difference among these isoforms in their ability to process POMC in the transfected cells. Since truncation of PC1/3 in its C-terminal region reportedly renders the enzyme unstable, we speculate that the accentuated processing of the triple variant in this region may, in vivo, create a subtle deficit of PC1/3 enzymatic activity in endocrine and neuroendocrine cells, causing impaired processing of prohormones and proneuropeptides to their bioactive forms. Copyright © 2011 Elsevier Inc. All rights reserved.

Anticholinesterase, antioxidant, analgesic and anti-inflammatory activity assessment of Xeranthemum annuum L. and isolation of two cyanogenic compounds.

PubMed

Orhan, Ilkay Erdogan; Gulyurdu, Fulya; Kupeli Akkol, Esra; Senol, Fatma Sezer; Arabaci Anul, Serap; Tatli, Iffet Irem

2016-11-01

Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data. Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root-stem (R-S) extracts of XA. Anticholinesterase (at 100 μg mL -1 ) and antioxidant (at 1000 μg mL -1 ) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200 mg kg -1 ) and p-benzoquinone (PBQ) writhing models (200 mg kg -1 ) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods. Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.85 ± 0.94% and 96.89 ± 1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33 ± 1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79 ± 0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract. This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.

Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans

PubMed Central

Tang, Weihong; Cushman, Mary; Green, David; Rich, Stephen S.; Lange, Leslie A.; Yang, Qiong; Tracy, Russell P.; Tofler, Geoffrey H.; Basu, Saonli; Wilson, James G.; Keating, Brendan J.; Weng, Lu-Chen; Taylor, Herman A.; Jacobs, David R.; Delaney, Joseph A.; Palmer, Cameron D.; Young, Taylor; Pankow, James S.; O'Donnell, Christopher J.; Smith, Nicholas L.; Reiner, Alexander P.; Folsom, Aaron R.

2016-01-01

Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 × 10−7 in EAs and P=3.88 × 10−3 in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 × 10−9 in EAs and P=2.98 × 10−2 in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 × 10−10), with VWF rs1800380 in AAs (P=5.62 × 10−11), and with MAT1A rs2236568 in AAs (P=1.69 × 10−6). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs. PMID:25779970

Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

PubMed

Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

2014-05-01

Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

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

Li, Mi; University of Chinese Academy of Sciences, Beijing 100049; Liu, Lianqing, E-mail: lqliu@sia.cn

Highlights: •Nanoscale cellular ultra-structures of macrophages were observed. •The binding affinities of FcγRs were measured directly on macrophages. •The nanoscale distributions of FcγRs were mapped on macrophages. -- Abstract: Fc gamma receptors (FcγR), widely expressed on effector cells (e.g., NK cells, macrophages), play an important role in clinical cancer immunotherapy. The binding of FcγRs to the Fc portions of antibodies that are attached to the target cells can activate the antibody-dependent cell-mediated cytotoxicity (ADCC) killing mechanism which leads to the lysis of target cells. In this work, we used atomic force microscopy (AFM) to observe the cellular ultra-structures and measuremore » the biophysical properties (affinity and distribution) of FcγRs on single macrophages in aqueous environments. AFM imaging was used to obtain the topographies of macrophages, revealing the nanoscale cellular fine structures. For molecular interaction recognition, antibody molecules were attached onto AFM tips via a heterobifunctional polyethylene glycol (PEG) crosslinker. With AFM single-molecule force spectroscopy, the binding affinities of FcγRs were quantitatively measured on single macrophages. Adhesion force mapping method was used to localize the FcγRs, revealing the nanoscale distribution of FcγRs on local areas of macrophages. The experimental results can improve our understanding of FcγRs on macrophages; the established approach will facilitate further research on physiological activities involved in antibody-based immunotherapy.« less

Regulation of the calcium release channel from rabbit skeletal muscle by the nucleotides ATP, AMP, IMP and adenosine.

PubMed

Laver, D R; Lenz, G K; Lamb, G D

2001-12-15

1. Nucleotide activation of skeletal muscle ryanodine receptors (RyRs) was studied in planar lipid bilayers in order to understand RyR regulation in vivo under normal and fatigued conditions. With 'resting' calcium (100 nM cytoplasmic and 1 mM luminal), RyRs had an open probability (P(o)) of approximately 0.01 in the absence of nucleotides and magnesium. ATP reversibly activated RyRs with P(o) at saturation (P(max)) approximately 0.33 and K(a) (concentration for half-maximal activation) approximately 0.36 mM and with a Hill coefficient (n(H)) of approximately 1.8 in RyRs when P(max) < 0.5 and approximately 4 when P(max) > 0.5. 2. AMP was a much weaker agonist (P(max) approximately 0.09) and adenosine was weaker still (P(max) approximately 0.01-0.02), whereas inosine monophosphate (IMP), the normal metabolic end product of ATP hydrolysis, produced no activation at all. 3. Adenosine acted as a competitive antagonist that reversibly inhibited ATP- and AMP-activated RyRs with n(H) approximately 1 and K(i) approximately 0.06 mM at [ATP] < 0.5 mM, increasing 4-fold for each 2-fold increase in [ATP] above 0.5 mM. This is explained by the binding of a single adenosine preventing the cooperative binding of two ATP or AMP molecules, with dissociation constants of 0.4, 0.45 and 0.06 mM for ATP, AMP and adenosine, respectively. Importantly, IMP (< or = 8 mM) had no inhibitory effect whatsoever on ATP-activated RyRs. 4. Mean open (tau(o)) and closed (tau(c)) dwell-times were more closely related to P(o) than to the nucleotide species or individual RyRs. At P(o) < 0.2, RyR regulation occurred via changes in tau(c), whereas at higher P(o) this also occurred via changes in tau(o). The detailed properties of activation and competitive inhibition indicated complex channel behaviour that could be explained in terms of a model involving interactions between different subunits of the RyR homotetramer. 5. The results also show how deleterious adenosine accumulation is to the function of RyRs in skeletal muscle and, by comparison with voltage sensor-controlled Ca(2+) release, indicate that voltage sensor activation requires ATP binding to the RyR to be effective.

Role of Sequence Variations in AhR Gene Towards Modulating Smoking Induced Lung Cancer Susceptibility in North Indian Population: A Multiple Interaction Analysis.

PubMed

Budhwar, Sneha; Bahl, Charu; Sharma, Siddharth; Singh, Navneet; Behera, Digambar

2018-05-01

AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer. To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility. 297 cases and 320 controls have been genotyped using PCR-RFLP technique. In order to find out the association, unconditional logistic regression approach was used. To analyze high order in-teractions Multifactor Dimensionality Reduction and Classification and regression tree was used. Subjects carrying the variant genotype for AhR rs7811989 showed a two-fold risk (p=0.007) and a marginal risk was also seen in case of individuals carrying either single or double copy of suscep-tible allele for rs102550822 (p=0.02). Whereas the variant allele for rs2066853 showcased a strong pro-tective effect (p=0.003). SQCC individuals with mutant genotype of rs2066853 also exhibited a protec-tive effect towards lung cancer (OR=0.30, p=0.0013). The association of rs7811989 mutant genotype and rs10250822 mutant genotype was evident especially in smokers as compared to non-smokers. AhR rs2066853 showed a decreased risk in smokers with mutant genotype (p=0.002). MDR approach gave the best interaction model of AhR rs2066853 and smoking (CVC=10/10, prediction error=0.42). AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.

Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus

PubMed Central

Dennis, Siobhan H.; Pasqui, Francesca; Colvin, Ellen M.; Sanger, Helen; Mogg, Adrian J.; Felder, Christian C.; Broad, Lisa M.; Fitzjohn, Steve M.; Isaac, John T.R.; Mellor, Jack R.

2016-01-01

Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans. PMID:26472558

Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.

PubMed

Jocks, T; Freudenberg, J; Zahner, G; Stahl, R A

1998-01-01

These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.

Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism.

PubMed

Löffler, Dennis; Behrendt, Susanne; Creemers, John W M; Klammt, Jürgen; Aust, Gabriela; Stanik, Juraj; Kiess, Wieland; Kovacs, Peter; Körner, Antje

2017-03-01

Variants in Proprotein Convertase Subtilisin/Kexin Type 1 ( PCSK1 ) may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C) by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER) causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5' end did not affect PCSK1 promoter activity. In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children.

Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations.

PubMed

Song, Pu; Li, Kai; Liu, Ling; Wang, Xiaowen; Jian, Zhe; Zhang, Weigang; Wang, Gang; Li, Chunying; Gao, Tianwen

2016-10-01

The nuclear factor erythroid-derived two-like 2-antioxidant response element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1 (HMOX1 or HO-1) play essential roles in H2 O2 -induced oxidative damage in human melanocytes. However, the link between Nrf2 promoter polymorphisms and susceptibility to oxidative stress-related diseases such as vitiligo is unknown. This study evaluated the association of the Nrf2 and HO-1 genes polymorphisms with vitiligo susceptibility. In this case-control study of 1136 Han Chinese vitiligo patients and 1200 controls, Nrf2 (rs35652124 and rs6721961) and HO-1 (rs2071746) genes were genotyped by PCR-restriction fragment length polymorphism analysis. Overall, a significantly decreased risk of vitiligo was found to be associated with Nrf2 rs35652124 CC and combined (CT+CC) genotypes [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.83 and OR, 0.84, 95% CI 0.71-0.99, respectively], as well as among subgroups: female, onset age ≤20 and never smoker. We subsequently found that Nrf2 rs35652124 C allele had higher transcriptional activity in the luciferase reporter assay compared with Nrf2 rs35652124 T allele. Furthermore, we investigated serum HO-1 activity was associated with the rs35652124 CT+CC genotype and lower in patients than in controls (P = 0.024). Logistic regression analysis showed a dose-response relationship between lower vitiligo risk and increased HO-1 activity in rs35652124 CT+CC genotype carriers (Ptrend < 0.05). These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula.

PubMed

Arias, Hugo R; Jin, Xiaotao; Feuerbach, Dominik; Drenan, Ryan M

2017-11-01

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca 2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca 2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC]>(+)-catharanthine>(±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine>(±)-18-MC>(±)-18-HC>(±)-18-MAC. Interestingly, the inhibitory potency of (+)-catharanthine (27±4μM) and (±)-18-MC (28±6μM) on MHb (VI) neurons was lower than that observed on hα3β4 AChRs, suggesting that these compounds inhibit a variety of endogenous α3β4* AChRs. In addition, the interaction of bupropion with (-)-ibogaine sites on hα3β4 AChRs is tested by [ 3 H]ibogaine competition binding experiments. The results indicate that bupropion binds to ibogaine sites at desensitized hα3β4 AChRs with 2-fold higher affinity than at resting receptors, suggesting that these compounds share the same binding sites. In conclusion, coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to other AChRs, by interacting with the bupropion (luminal) site. Coronaridine congeners also inhibit α3β4*AChRs expressed in MHb (VI) neurons, supporting the notion that these receptors are important endogenous targets for their anti-addictive activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula

PubMed Central

Arias, Hugo R.; Jin, Xiaotao; Feuerbach, Dominik; Drenan, Ryan M.

2018-01-01

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC] > (+)-catharanthine > (±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine > (±)-18-MC > (±)-18-HC > (±)-18-MAC. Interestingly, the inhibitory potency of (+)-catharanthine (27 ± 4 μM) and (±)-18-MC (28 ± 6 μM) on MHb (VI) neurons was lower than that observed on hα3β4 AChRs, suggesting that these compounds inhibit a variety of endogenous α3β4* AChRs. In addition, the interaction of bupropion with (−)-ibogaine sites on hα3β4 AChRs is tested by [3H]ibogaine competition binding experiments. The results indicate that bupropion binds to ibogaine sites at desensitized hα3β4 AChRs with 2-fold higher affinity than at resting receptors, suggesting that these compounds share the same binding sites. In conclusion, coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to other AChRs, by interacting with the bupropion (luminal) site. Coronaridine congeners also inhibit α3β4*AChRs expressed in MHb (VI) neurons, supporting the notion that these receptors are important endogenous targets for their anti-addictive activities. PMID:29042244

The Caltech-NRAO Stripe 82 Survey (CNSS) Paper. I. The Pilot Radio Transient Survey in 50 Deg.(exp. 2)

NASA Technical Reports Server (NTRS)

Mooley, K. P.; Hallinan, G.; Bourke, S.; Horesh, A.; Myers, S. T.; Frail, D. A.; Kulkarni, S. R.; Levitan, D. B.; Kasliwal, M. M.; Cenko, S. B.;

An Extensive Census of Hubble Space Telescope Counterparts to Chandra X-Ray Sources in the Globular Cluster 47 Tucanae. I. Astrometry and Photometry

NASA Astrophysics Data System (ADS)

Edmonds, Peter D.; Gilliland, Ronald L.; Heinke, Craig O.; Grindlay, Jonathan E.

2003-10-01

We report in this study of 47 Tucanae the largest number of optical identifications of X-ray sources yet obtained in a single globular cluster. Using deep Chandra ACIS-I imaging and extensive Hubble Space Telescope studies with Wide Field Planetary Camera 2 (WFPC2; including a 120 orbit program giving superb V and I images), we have detected optical counterparts to at least 22 cataclysmic variables (CVs) and 29 chromospherically active binaries (BY Dra and RS CVn systems) in 47 Tuc. These identifications are all based on tight astrometric matches between X-ray sources and objects with unusual (non-main-sequence [non-MS]) optical colors and/or optical variability. Several other CVs and active binaries have likely been found, but these have marginal significance because of larger offsets between the X-ray and optical positions, or colors and variability that are not statistically convincing. These less secure optical identifications are not subsequently discussed in detail. In the U versus U-V color-magnitude diagram (CMD), where the U band corresponds to either F336W or F300W, the CVs all show evidence for blue colors compared with the MS, but most of them fall close to the main sequence in the V versus V-I CMD, showing that the secondary stars dominate the optical light. The X-ray-detected active binaries have magnitude offsets above the MS (in both the U versus U-V or V versus V-I CMDs) that are indistinguishable from those of the much larger sample of optical variables (eclipsing and contact binaries and BY Dra variables) detected in the recent WFPC2 studies of Albrow et al. We also present the results of a new, deeper search for optical companions to millisecond pulsars (MSPs). One possible optical companion to an MSP (47 Tuc T) was found, adding to the two optical companions already known. Finally, we study several blue stars with periodic variability from Albrow et al. that show little or no evidence for X-ray emission. The optical colors of these objects differ from those of 47 Tuc (and field) CVs. An accompanying paper will present time series results for these optical identifications and will discuss X-ray-to-optical flux ratios, spatial distributions, and an overall interpretation of the results. Based on observations with the NASA/ESA Hubble Space Telescope obtained at STScI, which is operated by AURA, Inc., under NASA contract NAS 5-26555.

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.

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

Active cigarette smoking and the risk of breast cancer at the level of N-acetyltransferase 2 (NAT2) gene polymorphisms.

PubMed

Kasajova, Petra; Holubekova, Veronika; Mendelova, Andrea; Lasabova, Zora; Zubor, Pavol; Kudela, Erik; Biskupska-Bodova, Kristina; Danko, Jan

2016-06-01

The aim of our study was to assess the correlation between the tobacco exposure and NAT2 gene (rs1041983 C/T, rs1801280 T/C, rs1799930 G/A) polymorphisms in association with breast cancer development. We wanted to determine the prognostic clinical importance of these polymorphisms in association with smoking and breast cancer. For the detection of possible association between smoking, NAT2 gene polymorphisms, and the risk of breast cancer, we designed a case-controlled study with 198 patients enrolled, 98 breast cancer patients and 100 healthy controls. Ten milliliters of peripheral blood from the cubital vein was withdrawn from every patient. The HRM (high resolution melting) analysis was used for the detection of three abovementioned NAT2 gene polymorphisms. When comparing a group of women smoking more than 5 cigarettes a day with the patients smoking fewer than 5 cigarettes a day, we found out that if women were the carriers of aberrant AA genotype for rs1799930, the first group of women had higher risk of breast carcinoma than the second group. If patients were the carriers of aberrant TT genotype for rs1041983, for rs1801280CC genotype, and rs1799930AA genotype and they smoked more than 5 cigarettes a day, they had higher risk of malignant breast disease than never-smoking women. Our results confirm the hypothesis that NAT2 gene polymorphisms (rs1041983 C/T, rs1801280 T/C, and rs1799930 G/A) in association with long-period active smoking could be the possible individual risk-predicting factors for breast cancer development in the population of Slovak women.

The sigma-1 receptor: roles in neuronal plasticity and disease.

PubMed

Kourrich, Saïd; Su, Tsung-Ping; Fujimoto, Michiko; Bonci, Antonello

2012-12-01

Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. Sig-1Rs are intracellular chaperones that reside specifically at the endoplasmic reticulum (ER)-mitochondrion interface, referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER-mitochondrion Ca(2+) signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanisms linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating aspects of neurological and psychiatric diseases. Published by Elsevier Ltd.

Price Analysis on Commercial Item Purchases Within the Department of the Navy

DTIC Science & Technology

2014-05-22

workforce should also have the quantitative skills required to effectively perform its duties. The demands of the workforce have grown, with a 63...George Washington (CVN 73) as the sales officer and materials officer. Follow-on tours include food service officer for Joint Task Force Guantanamo...an overview of several reports and educational materials directed toward price reasonableness determinations. Section A focuses on the DODIG, the

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

DTIC Science & Technology

1984-12-01

part of a larger project involving development of a wide range of computer technologies, including artifcial intelligence and a long-range computer...shipboard manage- ment, aircraft management, expert systems, menu selection, man- machine interface, artificial intelligence , automation; shipboard It AWM...functions, planning, evaluation, training, hierarchical data bases The objective of this project was to conduct an evaluation of ZOG, a general purpose

The relationship between children's sensory processing patterns and their leisure preferences and participation patterns.

PubMed

Ismael, Noor T; Lawson, Lisa A Mische; Cox, Jane A

2015-12-01

Sensory processing patterns may be associated with children's preferences for different activities; however, knowledge about how different sensory processing patterns may relate to children's participation in leisure activities is scarce. This study investigated in what leisure activities children with extreme sensory processing patterns participate and if relationships exist between children's sensory processing patterns and their leisure preferences and participation patterns. This correlational study analyzed data from children's Sensory Profiles and reported play and leisure preferences. All 91 children in the sample completed the Children's Assessment for Participation and Enjoyment (CAPE) and the Preferences for Activities of Children (PAC). Parents of children ages 6 to 10 years completed the Sensory Profile, and children ages 11 to 14 years completed the Adolescent/Adult Sensory Profile. Children with different sensory processing patterns preferred both similar and distinct leisure activities. Low-registration quadrant summary z scores negatively correlated with CAPE overall diversity scores (rs=-.23, p=.03), sensitivity quadrant summary z scores negatively correlated with preferences for social activities (rs=-.23, p=.03) and preferences for skill-based activities (rs=-.22, p=.04), and avoiding quadrant summary z scores negatively correlated with preferences for social activities (rs=-.26, p=.01). Children's sensory preferences are related to leisure preferences and participation. © CAOT 2015.

Design project: LONGBOW supersonic interceptor

NASA Technical Reports Server (NTRS)

Stoney, Robert; Baker, Matt; Capstaff, Joseph G.; Dishman, Robert; Fick, Gregory; Frick, Stephen N.; Kelly, Mark

1993-01-01

A recent white paper entitled 'From the Sea' has spotlighted the need for Naval Aviation to provide overland support to joint operations. The base for this support, the Aircraft Carrier (CVN), will frequently be unable to operate within close range of the battleground because of littoral land-based air and subsurface threats. A high speed, long range, carrier capable aircraft would allow the CVN to provide timely support to distant battleground operations. Such an aircraft, operating as a Deck-Launched Interceptor (DLI), would also be an excellent counter to Next Generation Russian Naval Aviation (NGRNA) threats consisting of supersonic bombers, such as the Backfire, equipped with the next generation of high-speed, long-range missiles. Additionally, it would serve as an excellent high speed Reconnaissance airplane, capable of providing Battle Force commanders with timely, accurate pre-mission targeting information and post-mission Bomb Damage Assessment (BDA). Recent advances in computational hypersonic airflow modeling has produced a method of defining aircraft shapes that fit a conical shock flow model to maximize the efficiency of the vehicle. This 'Waverider' concept provides one means of achieving long ranges at high speeds. A Request for Proposal (RFP) was issued by Professor Conrad Newberry that contained design requirements for an aircraft to accomplish the above stated missions, utilizing Waverider technology.

Auxiliary basis sets for density-fitting second-order Møller-Plesset perturbation theory: weighted core-valence correlation consistent basis sets for the 4d elements Y-Pd.

PubMed

Hill, J Grant

2013-09-30

Auxiliary basis sets (ABS) specifically matched to the cc-pwCVnZ-PP and aug-cc-pwCVnZ-PP orbital basis sets (OBS) have been developed and optimized for the 4d elements Y-Pd at the second-order Møller-Plesset perturbation theory level. Calculation of the core-valence electron correlation energies for small to medium sized transition metal complexes demonstrates that the error due to the use of these new sets in density fitting is three to four orders of magnitude smaller than that due to the OBS incompleteness, and hence is considered negligible. Utilizing the ABSs in the resolution-of-the-identity component of explicitly correlated calculations is also investigated, where it is shown that i-type functions are important to produce well-controlled errors in both integrals and correlation energy. Benchmarking at the explicitly correlated coupled cluster with single, double, and perturbative triple excitations level indicates impressive convergence with respect to basis set size for the spectroscopic constants of 4d monofluorides; explicitly correlated double-ζ calculations produce results close to conventional quadruple-ζ, and triple-ζ is within chemical accuracy of the complete basis set limit. Copyright © 2013 Wiley Periodicals, Inc.

Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha. A possible link between xenobiotic response and nutritional state.

PubMed

Shiraki, Takuma; Sakai, Noriko; Kanaya, Eiko; Jingami, Hisato

2003-03-28

In contrast to the classical nuclear receptors, the constitutive androstane receptor (CAR) is transcriptionally active in the absence of ligand. In the course of searching for the mediator of CAR activation, we found that ligand-independent activation of CAR was achieved in cooperation with the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). PGC-1 beta, a PGC-1 alpha homologue, also activated CAR to less of an extent than PGC-1 alpha. Coexpression of the ligand-binding domain of a heterodimerization partner, retinoid X receptor alpha, enhanced the PGC-1 alpha-mediated activation of CAR, although it had a weak effect on the basal activity of CAR in the absence of PGC-1 alpha. Both the N-terminal region, with the LXXLL motif, and the C-terminal region, with a serine/arginine-rich domain (RS domain), in PGC-1 alpha were required for full activation of CAR. Pull-down experiments using recombinant proteins revealed that CAR directly interacted with both the LXXLL motif and the RS domain. Furthermore, we demonstrated that the RS domain of PGC-1 alpha was required for CAR localization at nuclear speckles. These results indicate that PGC-1 alpha mediates the ligand-independent activation of CAR by means of subnuclear targeting through the RS domain of PGC-1 alpha.

Histamine H4-Receptors Inhibit Mast Cell Renin Release in Ischemia/Reperfusion via Protein Kinase Cε-Dependent Aldehyde Dehydrogenase Type-2 Activation

PubMed Central

Aldi, Silvia; Takano, Ken-ichi; Tomita, Kengo; Koda, Kenichiro; Chan, Noel Y.-K.; Marino, Alice; Salazar-Rodriguez, Mariselis; Thurmond, Robin L.

2014-01-01

Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype–ε (PKCε)–aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow–derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCε and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCε and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure. PMID:24696042

Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity.

PubMed

de San Martin, Javier Zorrilla; Jalil, Abdelali; Trigo, Federico F

2015-12-01

Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release. It is usually assumed that activation of axonal GABA(A)Rs comes from spillover, but in cerebellar molecular layer interneurons (MLIs) the GABA source is different: in these cells, GABA release activates presynaptic GABA(A) autoreceptors (autoRs) together with postsynaptic targets, producing an autoR-mediated synaptic event. The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity. Here, we used local Ca(2+) photolysis in MLI axons of juvenile rats to evoke GABA release from individual varicosities to study the activation of axonal autoRs in single release sites. Our data show that single-site autoR conductances are similar to postsynaptic dendritic conductances. In conditions of high [Cl(-)](i), autoR-mediated conductances range from 1 to 5 nS; this corresponds to ∼30-150 GABA(A) channels per presynaptic varicosity, a value close to the number of channels in postsynaptic densities. Voltage responses produced by the activation of autoRs in single varicosities are amplified by a Na(v)-dependent mechanism and propagate along the axon with a length constant of 91 µm. Immunolabeling determination of synapse location shows that on average, one third of the synapses produce autoR-mediated signals that are large enough to reach the axon initial segment. Finally, we show that single-site activation of presynaptic GABA(A) autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity. © 2015 Zorrilla de San Martin et al.

Effects of morphine on stress induced anxiety in rats: role of nitric oxide and Hsp70.

PubMed

Joshi, Jagdish C; Ray, Arunabha; Gulati, Kavita

2015-02-01

The present study evaluated the effects of morphine on acute and chronic restraint stress (RS) induced anxiety modulation and the possible involvement of nitric oxide (NO) and heat shock proteins (Hsp70) during such effects. Acute RS (×1) induced anxiogenesis in the elevated plus maze (EPM) test which was associated with lowered brain NO metabolites (NOx) and elevated Hsp70 levels. Pretreatment with morphine (1 and 5 mg/kg) and L-arginine (500 mg/kg) attenuated the RS effects on EPM activity and brain NOx, whereas, Hsp70 levels were further augmented. Co-administration of both agents showed synergistic effects. By contrast, repeated RS (×15) did not induce any significant changes in EPM activity or brain NOx, but brain Hsp70 levels stayed elevated. Administration of morphine or L-arginine prior to chronic RS did not influence such chronic stress induced changes in behavioral and biochemical markers, but appreciably attenuated chronic RS induced elevation in Hsp70 levels. These results suggest that acute and chronic RS induced anxiety modulations were differentially influenced by morphine and L-arginine and that complex interactions involving brain NO and unregulated Hsp70 could regulate such effects. Copyright © 2014. Published by Elsevier Inc.

Association analysis between mitogen-activated protein/extracellular signal-regulated kinase (MEK) gene polymorphisms and depressive disorder in the Han Chinese population.

PubMed

Hu, Yingyan; Hong, Wu; Smith, Alicia; Yu, Shunying; Li, Zezhi; Wang, Dongxiang; Yuan, Chengmei; Cao, Lan; Wu, Zhiguo; Huang, Jia; Fralick, Drew; Phillips, Michael Robert; Fang, Yiru

2017-11-01

Recent research findings suggest that BDNF and BDNF signaling pathways participate in the development of major depressive disorder. Mitogen-activated extracellular signal-regulated kinase (MEK) is the most important kinase in the extracellular signal-regulated kinase pathway, and the extracellular signal-regulated kinase pathway is the key signaling pathway of BDNF, so it may play a role in development of depressive disorder. The aim of this study is to investigate the association between polymorphisms of the MAP2K1 (also known as MEK) gene and depressive disorder. Three single nucleotide polymorphisms (SNPs), were significantly associated with depressive disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p = 0.039). When subdividing the sample by gender, two of the SNPs remained statistically associated with depressive disorder in females: rs1549854 (p = 0.013) and rs1432441 (p = 0.04). The rs1549854 and rs1432441 polymorphisms of the MAP2K1 gene may be associated with major depressive disorder, especially in females. This study is the first to report that the MAP2K1 gene may be a genetic marker for depressive disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Is generic physical activity or specific exercise associated with motor abilities?

PubMed

Rinne, Marjo; Pasanen, Matti; Miilunpalo, Seppo; Mälkiä, Esko

2010-09-01

Evidence of the effect of leisure time physical activity (LTPA) modes on the motor abilities of a mature population is scarce. The purpose of this study was to compare the motor abilities of physically active and inactive men and women and to examine the associations of different exercise modes and former and recent LTPA (R-LTPA) with motor ability and various physical tests. The LTPA of the participants (men n = 69, women n = 79; aged 41-47 yr) was ascertained by a modified Physical Activity Readiness Questionnaire, including questions on the frequency, duration, and intensity of R-LTPA and former LTPA and on exercise modes. Motor abilities in terms of balance, agility, and coordination were assessed with a battery of nine tests supplemented with five physical fitness tests. Multiple statistical methods were used in analyses that were conducted separately for men and women. The MET-hours per week of R-LTPA correlated statistically significantly with the tests of agility and static balance (rs = -0.28, P = 0.022; rs = -0.25, P = 0.043, respectively) among men and with the static balance (rs = 0.41), 2-km walking (rs = 0.36), step squat (rs = 0.36) (P < or = 0.001, respectively), and static back endurance (rs = 0.25, P = 0.024) among women. In the stepwise regression among men, the most frequent statistically significant predictor was the playing of several games. For women, a history of LTPA for more than 3 yr was the strongest predictor for good results in almost all tests. Participants with long-term and regular LTPA had better motor performance, and especially a variety of games improve components of motor ability. Diverse, regular, and long-term exercise including both specific training and general activity develops both motor abilities and physical fitness.

Heterologous expression and biochemical characterization of a GHF9 endoglucanase from the termite Reticulitermes speratus in Pichia pastoris.

PubMed

Zhang, Pengfei; Yuan, Xianghua; Du, Yuguang; Li, Jian-Jun

2018-06-01

Cellulases are of great significance for full utilization of lignocellulosic biomass. Termites have an efficient ability to degrade cellulose. Heterologous production of the termite-origin cellulases is the first step to realize their industrial applications. The use of P. pastoris for the expression of recombinant proteins has become popular. The endoglucanase from Reticulitermes speratus (RsEG), belonging to glycoside hydrolase family 9 (GHF9), has not been produced in P. pastoris yet. A mutant RsEG m (G91A/Y97W/K429A) was successfully overexpressed in P. pastoris. RsEG m , with optimum pH 5.0, was active over the pH range of 4.0 to 9.0, and exhibited superior pH stability over between pH 4.0 and pH 11.0. It displayed the highest activity and good stability at 40 °C, but lost activity quickly at 50 °C. The apparent kinetic parameters of RsEG m against Carboxymethyl Cellulose (CMC) were determined, with K m and V max of 7.6 mg/ml and 5.4 μmol/min•mg respectively. Co 2+ , Mn 2+ and Fe 2+ enhanced the activity of RsEG m by 32.0, 19.5 and 11.2% respectively, while Pb 2+ and Cu 2+ decreased its activity by 19.6 and 12.7% separately. RsEG m could be overexpressed in P. pastoris. It was stable between pH 4.0 and pH 11.0, and exhibited higher stability at temperatures ≤ 40 °C. This endoglucanase may have potential to be used in the field of laundry, textile and lignocellulose-based biofuels and chemicals.

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.

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

Physical Activity Modifies the Effect of LPL, LIPC and CETP polymorphisms on HDL-C Levels and the Risk of Myocardial Infarction in Caucasian Women

PubMed Central

Ahmad, Tariq; Chasman, Daniel I.; Buring, Julie E.; Lee, I-Min; Ridker, Paul M; Everett, Brendan M.

2010-01-01

Background Recent genome-wide association studies have identified common variants associated with high-density lipoprotein cholesterol (HDL-C). Whether these associations are modified by physical activity, which increases HDL-C levels and reduces the risk of cardiovascular disease (CVD), is uncertain. Methods and Results In a prospective cohort study of 22,939 apparently healthy Caucasian US women, we selected 58 single nucleotide polymorphisms (SNPs) in 9 genes that demonstrated genome-wide association (P<5×10−8) with HDL-C levels and sought evidence of effect modification according to levels of physical activity (PA). PA modified the effects on HDL-C of 7 SNPs at 3 loci, and the strongest evidence of effect was observed for rs10096633 at LPL, rs1800588 at LIPC and rs1532624 at CETP (each P-interaction <0.05). The per-minor-allele increase in HDL-C for rs1800588 at LIPC and rs1532624 at CETP was greater in active than inactive women, whereas the reverse was observed for rs10096633 at LPL. Minor-allele carrier status at the LPL SNP was associated with a reduced risk of MI in active (Hazard Ratio [HR] 0.42, 95% Confidence Interval [CI] 0.23–0.76) but not amongst inactive women (HR 1.10, 95% CI 0.83–1.44; P-interaction=0.007). By contrast, carrier status at the CETP SNP was associated with a reduced risk of MI regardless of activity level (HR 0.72, 95% CI 0.57–0.92; P-interaction=0.71). No association between LIPC SNP carrier status and MI risk was noted Conclusions The effects of common variants in the LPL, LIPC and CETP genes on HDL-C levels are modified by PA. For a common variant in LPL, the impact on MI varied by activity level, while the effects of a common variant in CETP on MI risk did not. PMID:21252145

Characteristics of Metroxylon sagu resistant starch type III as prebiotic substance.

PubMed

Zi-Ni, Tan; Rosma, Ahmad; Napisah, Hussin; Karim, Alias A; Liong, Min-Tze

2015-04-01

Resistant starch type III (RS3 ) was produced from sago (Metroxylon sagu) and evaluated for its characteristics as a prebiotic. Two RS3 samples designated sago RS and HCl-sago RS contained 35.71% and 68.30% RS, respectively, were subjected to hydrolyses by gastric juice and digestive enzymes and to absorption. Both sago RS and HCl-sago RS were resistant to 180 min hydrolysis by gastric acidity at pH 1 to 4 with less than 0.85% hydrolyzed. Both samples were also resistant toward hydrolysis by gastrointestinal tract enzymes and intestinal absorption with 96.75% and 98.69% of RS3 were recovered respectively after 3.5 h digestion and overnight dialysis at 37 °C. Sago RS3 supported the growth of both beneficial (lactobacilli and Bifidobacteria) and pathogenic microbes (Escherichia coli, Campylobacter coli, and Clostridium perfringens) in the range of 2.60 to 3.91 log10 CFU/mL. Hence, prebiotic activity score was applied to describe the extent to which sago RS3 supports selective growth of the lactobacilli and bifidobacteria strains over pathogenic bacteria. The highest scores were obtained from Bifidobacterium sp. FTDC8943 grown on sago RS (+0.26) and HCl-sago RS (+0.24) followed by L. bulgaricus FTDC1511 grown on sago RS (+0.21). The findings had suggested that sago RS3 has the prebiotic partial characteristics and it is suggested to further assess the suitability of sago RS3 as a prebiotic material. © 2015 Institute of Food Technologists®

Programming Post-Translational Control over the Metabolic Labeling of Cellular Proteins with a Noncanonical Amino Acid.

PubMed

Thomas, Emily E; Pandey, Naresh; Knudsen, Sarah; Ball, Zachary T; Silberg, Jonathan J

2017-08-18

Transcriptional control can be used to program cells to label proteins with noncanonical amino acids by regulating the expression of orthogonal aminoacyl tRNA synthetases (aaRSs). However, we cannot yet program cells to control labeling in response to aaRS and ligand binding. To identify aaRSs whose activities can be regulated by interactions with ligands, we used a combinatorial approach to discover fragmented variants of Escherichia coli methionyl tRNA synthetase (MetRS) that require fusion to associating proteins for maximal activity. We found that these split proteins could be leveraged to create ligand-dependent MetRS using two approaches. When a pair of MetRS fragments was fused to FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were introduced that direct substrate specificity toward azidonorleucine (Anl), Anl metabolic labeling was significantly enhanced in growth medium containing rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS fragments to the termini of the ligand-binding domain of the estrogen receptor yielded proteins whose Anl metabolic labeling was significantly enhanced when 4-hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest that split MetRS can be fused to a range of ligand-binding proteins to create aaRSs whose metabolic labeling activities depend upon post-translational interactions with ligands.

The autoimmune disease-associated SNP rs917997 of IL18RAP controls IFNγ production by PBMC.

PubMed

Myhr, Courtney B; Hulme, Maigan A; Wasserfall, Clive H; Hong, Peter J; Lakshmi, Priya Saikumar; Schatz, Desmond A; Haller, Michael J; Brusko, Todd M; Atkinson, Mark A

2013-08-01

Type 1 Diabetes (T1D) is an autoimmune disorder characterized by aberrant T cell responses. Innate immune activation defects may facilitate a T helper 1 (Th1) phenotype. The cytokine IL-18 synergizes with IL-12 to induce IFNγ production and Th1 differentiation. The IL-18R subunit (IL18RAP) SNP rs917997 has been linked to decreased IL18RAP gene expression. Prior reports link rs917997 allele A with protection from T1D, and conversely with susceptibility to Celiac disease. However, few studies have investigated the IL-18 pathway in T1D. In this study, we analyzed responsiveness to IL-18 in T1D, and the effect of rs917997 genotype on IL18RAP gene expression post-activation. Upon IL-12 and IL-18 treatment, peripheral blood mononuclear cells from subjects carrying susceptibility alleles at rs917997 produced higher levels of IFNγ than those with protective genotypes. Additionally, the SNP modified IL18RAP surface protein expression by NK cells and gene expression in activated T cells. Taken together, these data suggest that the disease-associated rs917997 allele G permits hyperresponsiveness to IL-18, providing a novel target for therapeutic intervention in T1D. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Microbiota and Abundance of the Class 1 Integron-Integrase Gene in Tropical Sewage Treatment Plant Influent and Activated Sludge

PubMed Central

Paiva, Magna C.; Ávila, Marcelo P.; Reis, Mariana P.; Costa, Patrícia S.; Nardi, Regina M. D.; Nascimento, Andréa M. A.

2015-01-01

Bacteria are assumed to efficiently remove organic pollutants from sewage in sewage treatment plants, where antibiotic-resistance genes can move between species via mobile genetic elements known as integrons. Nevertheless, few studies have addressed bacterial diversity and class 1 integron abundance in tropical sewage. Here, we describe the extant microbiota, using V6 tag sequencing, and quantify the class 1 integron-integrase gene (intI1) in raw sewage (RS) and activated sludge (AS). The analysis of 1,174,486 quality-filtered reads obtained from RS and AS samples revealed complex and distinct bacterial diversity in these samples. The RS sample, with 3,074 operational taxonomic units, exhibited the highest alpha-diversity indices. Among the 25 phyla, Proteobacteria, Bacteroidetes and Firmicutes represented 85% (AS) and 92% (RS) of all reads. Increased relative abundance of Micrococcales, Myxococcales, and Sphingobacteriales and reduced pathogen abundance were noted in AS. At the genus level, differences were observed for the dominant genera Simplicispira and Diaphorobacter (AS) as well as for Enhydrobacter (RS). The activated sludge process decreased (55%) the amount of bacteria harboring the intI1 gene in the RS sample. Altogether, our results emphasize the importance of biological treatment for diminishing pathogenic bacteria and those bearing the intI1 gene that arrive at a sewage treatment plant. PMID:26115093

Capsaicin-induced glutamate release is implicated in nociceptive processing through activation of ionotropic glutamate receptors and group I metabotropic glutamate receptor in primary afferent fibers.

PubMed

Jin, You-Hong; Yamaki, Fumiko; Takemura, Motohide; Koike, Yuichi; Furuyama, Akira; Yonehara, Norifumi

2009-02-01

Glutamate (Glu) is the major excitatory neurotransmitter in the central nervous system. The role of peripheral Glu and Glu receptors (GluRs) in nociceptive transmission is, however, still unclear. In the present study, we examined Glu levels released in the subcutaneous perfusate of the rat hind instep using a microdialysis catheter and the thermal withdrawal latency using the Plantar Test following injection of drugs associated with GluRs with/without capsaicin into the hindpaw. The injection of capsaicin into the rat hind instep caused an increase of Glu level in the s.c. perfusate. Capsaicin also significantly decreased withdrawal latency to irradiation. These effects of capsaicin were inhibited by pretreatment with capsazepine, a transient receptor potential vanilloid receptor 1 (TRPV1) competitive antagonist. Capsaicin-induced Glu release was also suppressed by combination with each antagonist of ionotropic GluRs (iGluRs: NMDA/AMPA receptors) and group I metabotropic GluR (mGluR), but not group II and group III mGluRs. Furthermore, these GluRs antagonists showed remarkable inhibition against capsaicin-induced thermal hyperalgesia. These results suggest that Glu is released from the peripheral endings of small-diameter afferent fibers by noxious stimulation and then activates peripheral iGluRs and group I mGluR in development and/or maintenance of nociception. Furthermore, the activation of peripheral NMDA/AMPA receptors and group I mGluR may be important in mechanisms whereby capsaicin evokes nociceptive responses.

Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.

PubMed

Yanagimachi, Masakatsu; Naruto, Takuya; Miyamae, Takako; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Sato, Hidenori; Goto, Hiroaki; Yokota, Shumpei

2011-04-01

Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS. Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls. There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001). IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

The Role of Peroxisome Proliferator-Activated Receptors and Their Transcriptional Coactivators Gene Variations in Human Trainability: A Systematic Review

PubMed Central

Petr, Miroslav; Zajac, Adam; Maciejewska-Skrendo, Agnieszka

2018-01-01

Background: The peroxisome proliferator-activated receptors (PPARA, PPARG, PPARD) and their transcriptional coactivators’ (PPARGC1A, PPARGC1B) gene polymorphisms have been associated with muscle morphology, oxygen uptake, power output and endurance performance. The purpose of this review is to determine whether the PPARs and/or their coactivators’ polymorphisms can predict the training response to specific training stimuli. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses, a literature review has been run for a combination of PPARs and physical activity key words. Results: All ten of the included studies were performed using aerobic training in general, sedentary or elderly populations from 21 to 75 years of age. The non-responders for aerobic training (VO2peak increase, slow muscle fiber increase and low-density lipoprotein decrease) are the carriers of PPARGC1A rs8192678 Ser/Ser. The negative responders for aerobic training (decrease in VO2peak) are carriers of the PPARD rs2267668 G allele. The negative responders for aerobic training (decreased glucose tolerance and insulin response) are subjects with the PPARG rs1801282 Pro/Pro genotype. The best responders to aerobic training are PPARGC1A rs8192678 Gly/Gly, PPARD rs1053049 TT, PPARD rs2267668 AA and PPARG rs1801282 Ala carriers. Conclusions: The human response for aerobic training is significantly influenced by PPARs’ gene polymorphism and their coactivators, where aerobic training can negatively influence glucose metabolism and VO2peak in some genetically-predisposed individuals. PMID:29762540

Understanding screen-related sedentary behavior and its contributing factors among school-aged children: a social-ecologic exploration.

PubMed

He, Meizi; Harris, Stewart; Piché, Leonard; Beynon, Charlene

2009-01-01

To explore the factors that contribute to children's screen-related sedentary (S-RS) behaviors. Elementary schools. A random sample of children in grades five and six and their parents. The outcome measure was children's S-RS activity level measured by a self-administered questionnaire. A full spectrum of potential contributing factors for children's S-RS behaviors was obtained through surveys. Multilevel linear regression methods were used to determine the associations between these factors and children's screen time (hours per day) and results were expressed as regression coefficients (g). Of 955 child-parent pairs in 14 participating schools, 508 pairs (53%) completed the surveys. At an intrapersonal level, protective factors included being a girl (g = -.71); belonging to a sports team inside (g = -.56) or outside (g = -.49) of school; having a negative attitude toward S-RS activities (g = -.13); and having a positive attitude toward physical activity (g = .48). At the interpersonal and social levels, parental leisure S-RS behaviors (g = .32) were positively associated, whereas strict parental rules on computer use (g = -.27) and family income (g = -.32) were inversely correlated with S-RS behavior. At the environmental level, the presence of TVs in children's bedrooms (g = .44) and owning videogame devices (g = .58) increased the risk of S-RS behaviors, whereas after school programs (g = - .86) and schools' participation in the Turn Off the Screen Week campaign (g = -.91) decreased the risk. Public health interventions should target multilevel factors, including increasing children's awareness, promoting parental involvement in healthy lifestyle pursuits, and creating less screenogenic environments.

ROSAT PSPC observations of two X-ray-faint early-type galaxies: NGC 4365 and NGC 4382

NASA Technical Reports Server (NTRS)

Fabbiano, G.; Kim, D.-W.; Trinchieri, G.

1994-01-01

We present the results of ROSAT Positive Sensitive Proportional Counter (PSPC) observations of the two early-type galaxies NGC 4365 and NGC 4382. These galaxies are among those observed with Einstein to have the lowest X-ray to optical flux ratios of early-type galaxies. The PSCP data show that for radii r greater than 50 arcsec the radial distributions of the X-ray surface brightness are consistent with the optical distributions of King (1978). We also find that these galaxies have X-ray spectra significantly different from those observed in X-ray-bright ellipticals, with a relative excess of counts detected in the softest spectral channels. This confirms earlier Einstein results. The characteristics of the ROSAT PSPC do not allow us to discriminate between possible spectral models. If we adopt a two-component thermal model on the grounds of physical plausibility, we find that the spectral data can be fitted with a very soft optically thin component, with kT approximately 0.2 keV, and a hard component with kT greater than (1.0-1.5) keV. The hard component has a luminosity consistent with that expected from the integrated emission of a population of low mass-X-ray binaries in these galaxies; the nature of the very soft component is more speculative. Candidates include the coronal emission of late-type stars, supersoft X-ray sources, RS CVn, and perhaps a hot Interstellar Medium (ISM). Alternatively, the spectal data may be fitted with a 0.6-1 keV bremsstrahlung spectrum (expontential plus Gaunt), and may suggest the presence of a totally new population of X-ray sources.

DNA Sequence Variants in PPARGC1A, a Gene Encoding a Coactivator of the ω-3 LCPUFA Sensing PPAR-RXR Transcription Complex, Are Associated with NV AMD and AMD-Associated Loci in Genes of Complement and VEGF Signaling Pathways

PubMed Central

SanGiovanni, John Paul; Chen, Jing; Sapieha, Przemyslaw; Aderman, Christopher M.; Stahl, Andreas; Clemons, Traci E.; Chew, Emily Y.; Smith, Lois E. H.

2013-01-01

Background Increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and use of peroxisome proliferator activator receptor (PPAR)-activating drugs are associated with attenuation of pathologic retinal angiogenesis. ω-3 LCPUFAs are endogenous agonists of PPARs. We postulated that DNA sequence variation in PPAR gamma (PPARG) co-activator 1 alpha (PPARGC1A), a gene encoding a co-activator of the LCPUFA-sensing PPARG-retinoid X receptor (RXR) transcription complex, may influence neovascularization (NV) in age-related macular degeneration (AMD). Methods We applied exact testing methods to examine distributions of DNA sequence variants in PPARGC1A for association with NV AMD and interaction of AMD-associated loci in genes of complement, lipid metabolism, and VEGF signaling systems. Our sample contained 1858 people from 3 elderly cohorts of western European ancestry. We concurrently investigated retinal gene expression profiles in 17-day-old neonatal mice on a 2% LCPUFA feeding paradigm to identify LCPUFA-regulated genes both associated with pathologic retinal angiogenesis and known to interact with PPARs or PPARGC1A. Results A DNA coding variant (rs3736265) and a 3'UTR-resident regulatory variant (rs3774923) in PPARGC1A were independently associated with NV AMD (exact P = 0.003, both SNPs). SNP-SNP interactions existed for NV AMD (P<0.005) with rs3736265 and a AMD-associated variant in complement factor B (CFB, rs512559). PPARGC1A influences activation of the AMD-associated complement component 3 (C3) promoter fragment and CFB influences activation and proteolysis of C3. We observed interaction (P≤0.003) of rs3736265 with a variant in vascular endothelial growth factor A (VEGFA, rs3025033), a key molecule in retinal angiogenesis. Another PPARGC1A coding variant (rs8192678) showed statistical interaction with a SNP in the VEGFA receptor fms-related tyrosine kinase 1 (FLT1, rs10507386; P≤0.003). C3 expression was down-regulated 2-fold in retinas of ω-3 LCPUFA-fed mice – these animals also showed 70% reduction in retinal NV (P≤0.001). Conclusion Ligands and co-activators of the ω-3 LCPUFA sensing PPAR-RXR axis may influence retinal angiogenesis in NV AMD via the complement and VEGF signaling systems. We have linked the co-activator of a lipid-sensing transcription factor (PPARG co-activator 1 alpha, PPARGC1A) to age-related macular degeneration (AMD) and AMD-associated genes. PMID:23335958

Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans

PubMed Central

Meyer-Lindenberg, A; Kolachana, B; Gold, B; Olsh, A; Nicodemus, KK; Mattay, V; Dean, M; Weinberger, DR

2009-01-01

In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. PMID:18490926

Central cholinergic regulation of respiration: nicotinic receptors

PubMed Central

Shao, Xuesi M; Feldman, Jack L

2009-01-01

Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4* nAChRs in the preBötzinger Complex (preBötC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBötC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic α4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS. PMID:19498418

αConotoxin ArIB[V11L,V16D] is a potent and selective antagonist at rat and human native α7 nicotinic acetylcholine receptors

PubMed Central

Innocent, Neal; Livingstone, Phil D.; Hone, Arik; Kimura, Atsuko; Young, Tracey; Whiteaker, Paul; McIntosh, J. Michael; Wonnacott, Susan

2008-01-01

A recently developed α-conotoxin, α-CtxArIB[V11L,V16D] is a potent and selective competitive antagonist at rat recombinant α7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. α7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues where they are implicated in a variety of functions. Here we evaluate this toxin at rat and human native nAChRs. Functional α7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 in rat PC12 cells and human SHSY5Y cells loaded with calcium indicators. α-CtxArIB[V11L,V16D] specifically inhibited α7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli (5-iodo-A-85380, nicotine or KCl) that did not activate α7 nAChRs were unaffected. Human α7 nAChRs were also sensitive to α-CtxArIB[V11L,V16D]: ACh-evoked currents in X. laevis oocytes expressing human α7 nAChRs were inhibited by α-CtxArIB[V11L,V16D] (IC50 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the timecourse of recovery from blockade of rat α7 nAChRs in PC12 cells. α-CtxArIB[V11L,V16D] inhibited human native α7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 plus PNU-120596. Rat brain α7 nAChRs contribute to dopamine release from striatal minces: α-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that α-CtxArIB[V11L,V16D] selectively inhibits human and rat native α7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating α7 nAChR functions. PMID:18664588

HD 129333: The Sun in its infancy

NASA Technical Reports Server (NTRS)

Dorren, J. David; Guinan, Edward F.

1994-01-01

HD 129333 is a remarkable young, nearby solar-type G star which offers a unique opportunity of studying the properties of the Sun at a time very shortly after in arrived on the main sequence. Its space motion suggest that it is a member of the Pleiades moving group, with an age of approximately 70 Myr; its lithium abundance is consistent with this. HD 129333 has the highest level of Ca II emission of any G star which is not a member of a close binary. Our observations in 1983 showed it to have low-amplitude (5%) light variations implying a rotation period of about 2.7 days, or about 10 times faster than the Sun. Modeling of the photometric variations on the assumption that they are due to starspots yields a spot temperature about 500 K cooler than the photosphere, and a coverage of about 6% of the stellar surface area. ROSAT observations in 1990 revealed the star to be an X-ray source, with an X-ray luminosity in the 0.2 to 2.4 keV range about 300 times that of the Sun. We have used International Ultraviolet Explorer (IUE) observations in conjuction with ground-based photometry to examine the magnetic activity of this star. The IUE emission-line fluxes reveal a level of chromospheric activity 3 to 20 times greater than the Sun's. The transition-region activity is 20 to 100 times that of the Sun. The activity level of HD 129333 is consistent with the Skumanich law relating activity to age, and with the rotation-activity relation, although it may be near saturation level. This star can yield valuable information about the magnetic dynamo of the young Sun, as well as about stellar dynamos in general. The 1988 IUE observations covered four phases of its rotational cycle. A phase dependence of the Mg II h and k emission flux suggests a close association of chromospheric plages with starspot regions at that time. Systematic variations in the mean brightness of HD 129333 between 1983 and 1993, and in the UV emission fluxes, indicate the presence of an activity cycle of an estimated 12 years' duration. HD 129333 is the first solar-type star other than RS CVn binaries for which luminosity variations provide evidence for a spot cycle. Unlike the Sun, which is brighter at activity maximum HD 129333 appears to be fainter when more heavily spotted. Although evolutionary models for the Sun suggest that it was about 30% less luminous at age 70 Myr, they give no information about the UV flux. Accordingly, we have used the 1988 IUE observations of HD 129333 to construct a model spectrum of the infant Sun, which can be used to provide a quantitative estimate of the UV flux in the early solar system.

Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

PubMed

Reyes, Adelfo; Huerta, Leticia; Alfaro, Marisol; Navarrete, Andrés

2010-11-01

Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

PubMed Central

Manning, Kathryn Y.; Rajakumar, Nagalingam; Gómez, Francisco A.; Soddu, Andrea; Borrie, Michael J.

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1–42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD. PMID:28582450

Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study.

PubMed

Ruiz, Jonatan R; Labayen, Idoia; Ortega, Francisco B; Legry, Vanessa; Moreno, Luis A; Dallongeville, Jean; Martínez-Gómez, David; Bokor, Szilvia; Manios, Yannis; Ciarapica, Donatella; Gottrand, Frederic; De Henauw, Stefaan; Molnár, Denes; Sjöström, Michael; Meirhaeghe, Aline

2010-04-01

To examine whether physical activity attenuates the effect of the FTO rs9939609 polymorphism on body fat estimates in adolescents. Cross-sectional study. Athens, Greece; Dortmund, Germany; Ghent, Belgium; Heraklion, Greece; Lille, France; Pécs, Hungary; Rome, Italy; Stockholm, Sweden; Vienna, Austria; and Zaragoza, Spain, from October 2006 to December 2007. Adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (n = 752). Physical activity. The FTO rs9939609 polymorphism was genotyped. Physical activity was assessed by accelerometry. We measured weight, height, waist circumference, and triceps and subscapular skinfolds; body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and body fat percentage were calculated. The A allele of the FTO polymorphism was significantly associated with higher BMI (+0.42 per risk allele), higher body fat percentage (+1.03% per risk allele), and higher waist circumference (+0.85 cm per risk allele). We detected significant or borderline gene x physical activity interactions for the studied body fat estimates (for interaction, P = .02, .06, and .10 for BMI, body fat percentage, and waist circumference, respectively). Indeed, the effect of the FTO rs9939609 polymorphism on these body fat parameters was much lower in adolescents who met the daily physical activity recommendations (ie, >/=60 min/d of moderate to vigorous physical activity) compared with those who did not: +0.17 vs +0.65 per risk allele in BMI, respectively; +0.40% vs +1.70% per risk allele in body fat percentage, respectively; and +0.60 vs +1.15 cm per risk allele in waist circumference, respectively. Adolescents meeting the daily physical activity recommendations may overcome the effect of the FTO rs9939609 polymorphism on obesity-related traits.

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease.

PubMed

Kazemifar, Samaneh; Manning, Kathryn Y; Rajakumar, Nagalingam; Gómez, Francisco A; Soddu, Andrea; Borrie, Michael J; Menon, Ravi S; Bartha, Robert

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

Vastus lateralis surface and single motor unit EMG following submaximal shortening and lengthening contractions.

PubMed

Altenburg, Teatske M; de Ruiter, Cornelis J; Verdijk, Peter W L; van Mechelen, Willem; de Haan, Arnold

2008-12-01

A single shortening contraction reduces the force capacity of muscle fibers, whereas force capacity is enhanced following lengthening. However, how motor unit recruitment and discharge rate (muscle activation) are adapted to such changes in force capacity during submaximal contractions remains unknown. Additionally, there is limited evidence for force enhancement in larger muscles. We therefore investigated lengthening- and shortening-induced changes in activation of the knee extensors. We hypothesized that when the same submaximal torque had to be generated following shortening, muscle activation had to be increased, whereas a lower activation would suffice to produce the same torque following lengthening. Muscle activation following shortening and lengthening (20 degrees at 10 degrees /s) was determined using rectified surface electromyography (rsEMG) in a 1st session (at 10% and 50% maximal voluntary contraction (MVC)) and additionally with EMG of 42 vastus lateralis motor units recorded in a 2nd session (at 4%-47%MVC). rsEMG and motor unit discharge rates following shortening and lengthening were normalized to isometric reference contractions. As expected, normalized rsEMG (1.15 +/- 0.19) and discharge rate (1.11 +/- 0.09) were higher following shortening (p < 0.05). Following lengthening, normalized rsEMG (0.91 +/- 0.10) was, as expected, lower than 1.0 (p < 0.05), but normalized discharge rate (0.99 +/- 0.08) was not (p > 0.05). Thus, muscle activation was increased to compensate for a reduced force capacity following shortening by increasing the discharge rate of the active motor units (rate coding). In contrast, following lengthening, rsEMG decreased while the discharge rates of active motor units remained similar, suggesting that derecruitment of units might have occurred.

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

USDA-ARS?s Scientific Manuscript database

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...

FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population.

PubMed

Mathias, Rasika A; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C; Chilton, Floyd H

2010-09-01

Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 x 10(-7) - 1.7 x 10(-8)) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the omega-6 series (P = 2.11 x 10(-13) - 1.8 x 10(-20)). The minor allele across all SNPs was consistently associated with decreased omega-6 PUFAs, with the exception of dihomo-gamma-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Delta-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA.

FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population[S

PubMed Central

Mathias, Rasika A.; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C.; Chilton, Floyd H.

2010-01-01

Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 × 10−7 – 1.7 × 10−8) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the ω-6 series (P = 2.11 × 10−13 – 1.8 × 10−20). The minor allele across all SNPs was consistently associated with decreased ω-6 PUFAs, with the exception of dihomo-γ-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Δ-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA. PMID:20562440

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

PubMed

Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Genetic Obesity Risk and Attenuation Effect of Physical Fitness in Mexican-Mestizo Population: a Case-Control Study.

PubMed

Costa-Urrutia, Paula; Abud, Carolina; Franco-Trecu, Valentina; Colistro, Valentina; Rodríguez-Arellano, Martha Eunice; Vázquez-Pérez, Joel; Granados, Julio; Seelaender, Marilia

2017-05-01

We analyzed commonly reported European and Asian obesity-related gene variants in a Mexican-Mestizo population through each single nucleotide polymorphism (SNP) and a genetic risk score (GRS) based on 23 selected SNPs. Study subjects were physically active Mexican-Mestizo adults (n  =  608) with body mass index (BMI) values from 18 to 55 kg/m 2 . For each SNP and for the GRS, logistic models were performed to test for simple SNP associations with BMI, fat mass percentage (FMP), waist circumference (WC), and the interaction with VO 2max and muscular endurance (ME). To further understand the SNP or GRS*physical fitness components, generalized linear models were performed. Obesity risk was significantly associated to 6 SNPs (ADRB2 rs1042713, APOB rs512535, PPARA rs1800206, TNFA rs361525, TRHR rs7832552 and rs16892496) after adjustment by gender, age, ancestry, VO 2max , and ME. ME attenuated the influence of APOB rs512535 and TNFA rs361525 on obesity risk in FMP. WC was significantly associated to GRS. Both ME and VO 2max attenuated GRS effect on WC. We report associations for 6 out of 23 SNPs and for the GRS, which confer obesity risk, a novel finding for Mexican-Mestizo physically active population. Also, the importance of including physical fitness components variables in obesity genetic risk studies is highlighted, with special regard to intervention purposes. © 2017 John Wiley & Sons Ltd/University College London.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

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

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsicmore » activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2 products. • JWH-018, JWH-073 and their human metabolites have high affinity for CB{sub 2} receptors. • JWH-018, JWH-073 and their human metabolites are potent agonists at CB{sub 2} receptors. • JWH-018, JWH-073 and their metabolites exhibit distinct CB{sub 2} signaling properties. • Studies of JWH-018 and JWH-073 should consider actions at CB{sub 1} and CB{sub 2} receptors.« less

Validity of retrospective disease activity assessment in systemic lupus erythematosus.

PubMed

Arce-Salinas, A; Cardiel, M H; Guzmán, J; Alcocer-Varela, J

1996-05-01

To evaluate the validity of retrospective disease activity assessment derived from clinical charts. We prospectively evaluated 37 patients with systemic lupus erythematosus (SLE) in 90 visits using the SLE Disease Activity Index (SLEDAI), the Mexican SLEDAI (Mex-SLEDAI), and the Lupus Activity Criteria Count (LACC) indices. Routine clinical observations were written by rheumatologists blind to index scores. These notes were reviewed 2 years later to obtain retrospective index scores and their validity was assessed using prospective scores as the standard. Statistical analysis was by Spearman's rank correlation coefficient (rs), Wilcoxon matched pairs test, kappa statistic, and intraclass correlation coefficient (ri). We calculated the sensitivity and specificity of retrospective indices to detect active disease. Median retrospective scores were lower in all indices: SLEDAI (4 VS 2, p =0.004, RS = 0.68, ri = 0.30); Mex-SLEDAI (2 vs 1, p < 0.0003, rs = 0.79, ri = 0.31); and LACC (1 vs 1, p = 0.007, rs = 0.65, ri = 0.21). Used to detect active SLE, the retrospective SLEDAI had a sensitivity of 0.68 and a specificity of 0.86; corresponding values for the Mex-SLEDAI were 0.72 and 0.91, and for the LACC, 0.77 and 0.76. Retrospective disease activity indices tended to provide lower scores than prospective evaluations. They often missed patients with mildly active disease, but when positive they were good predictors of disease activity.

[Gene-gene interaction on central obesity in school-aged children in China].

PubMed

Fu, L W; Zhang, M X; Wu, L J; Gao, L W; Mi, J

2017-07-10

Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified. Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method. A total of 6 single nucleotide polymorphisms ( FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Logistic regression model was used to investigate the association between 6 SNPs and central obesity. Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR. Results: After adjusting gender, age, Tanner stage, physical activity and family history of obesity, the FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model ( OR =1.24, 95 %CI : 1.06-1.45, P =0.008; OR =1.26, 95 %CI : 1.11-1.43, P =2.98×10(-4); OR =1.18, 95 % CI : 1.06-1.32, P =0.003). GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 ( P =0.001). The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539. This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender, age, Tanner stage, physical activity and family history of obesity. Conclusions: Our study showed that FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity, and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators

PubMed Central

Ng, Herman J.; Whittemore, Edward R.; Tran, Minhtam B.; Hogenkamp, Derk J.; Broide, Ron S.; Johnstone, Timothy B.; Zheng, Lijun; Stevens, Karen E.; Gee, Kelvin W.

2007-01-01

Activation of brain α7 nicotinic acetylcholine receptors (α7 nAChRs) has broad therapeutic potential in CNS diseases related to cognitive dysfunction, including Alzheimer's disease and schizophrenia. In contrast to direct agonist activation, positive allosteric modulation of α7 nAChRs would deliver the clinically validated benefits of allosterism to these indications. We have generated a selective α7 nAChR-positive allosteric modulator (PAM) from a library of GABAA receptor PAMs. Compound 6 (N-(4-chlorophenyl)-α-[[(4-chloro-phenyl)amino]methylene]-3-methyl-5-isoxazoleacet-amide) evokes robust positive modulation of agonist-induced currents at α7 nAChRs, while preserving the rapid native characteristics of desensitization, and has little to no efficacy at other ligand-gated ion channels. In rodent models, it corrects sensory-gating deficits and improves working memory, effects consistent with cognitive enhancement. Compound 6 represents a chemotype for allosteric activation of α7 nAChRs, with therapeutic potential in CNS diseases with cognitive dysfunction. PMID:17470817

Physicochemical evolution during rice straw and coal co-pyrolysis and its effect on co-gasification reactivity.

PubMed

Wei, Juntao; Gong, Yan; Guo, Qinghua; Ding, Lu; Wang, Fuchen; Yu, Guangsuo

2017-03-01

Physicochemical evolution (i.e. pore structure variation, carbon structure change and active AAEM transformation) during rice straw (RS) and Shenfu bituminous coal (SF) co-pyrolysis was quantitatively determined in this work. Moreover, the corresponding char gasification was conducted using a thermogravimetric analyzer (TGA) and relative reactivity was proposed to quantify the co-pyrolysis impact on co-gasification reactivity. The results showed that the development of pore structure in co-pyrolyzed chars was first inhibited and then enhanced with the decrease of SF proportion. The promotion effect of co-pyrolysis on order degree of co-pyrolyzed chars gradually weakened with increasing RS proportion. Co-pyrolysis mainly enhanced active K transformation in co-pyrolyzed chars and the promotion effect was alleviated with increasing RS proportion. The inhibition effect of co-pyrolysis on co-gasification reactivity weakened with increasing RS proportion and gasification temperature, which was mainly attributed to the combination of carbon structure evolution and active AAEM transformation in co-pyrolysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

PubMed Central

Savary, Etienne; Kullmann, Dimitri M.; Miles, Richard

2015-01-01

An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca2+ entry through Ca2+-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability. We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings. SIGNIFICANCE STATEMENT In the hippocampus, a form of NMDA receptor-independent long-term potentiation (LTP) occurs at excitatory synapses made on some inhibitory neurons. This is preferentially induced when postsynaptic interneurons are hyperpolarized, depends on Ca2+ entry through Ca2+-permeable AMPA receptors, and has been labeled anti-Hebbian LTP. Here we show that this form of LTP also depends on activation of both group I mGluR and M1 mAChRs. We demonstrate that these G-protein coupled receptors (GPCRs) interact, because the blockade of one receptor suppresses long-term effects of activation of the other GPCR on both LTP and interneuron membrane potential. This LTP was also detected in paired recordings, although only when both presynaptic and postsynaptic recordings did not perturb the intracellular medium. Changes in EPSP amplitude distributions in dual recordings were consistent with a presynaptic locus of expression. PMID:26446209

Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain.

PubMed

Viatchenko-Karpinski, Viacheslav; Novosolova, Natalia; Ishchenko, Yevheniia; Azhar, M Ameruddin; Wright, Michael; Tsintsadze, Vera; Kamal, Ahmed; Burnashev, Nail; Miller, Andrew D; Voitenko, Nana; Giniatullin, Rashid; Lozovaya, Natalia

2016-01-01

A growing body of evidence suggests that ATP-gated P2X3 receptors (P2X3Rs) are implicated in chronic pain. We address the possibility that stable, synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons. The effects of two stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter, the action of these stable, synthetic Ap4A analogs on inflammatory pain and thermal hyperalgesia is studied through the measurement of antinociceptive effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place mediated by high-affinity desensitization (at low concentrations; IC50 values 100-250 nM) giving way to only weak partial agonism at much higher concentrations (EC50 values ≥ 10 µM). Similar inhibitory activity is observed with human recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root, and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A analogs mediate clear inhibition of pain responses in both in vivo inflammation models. Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) being weak partial agonist provoke potent high-affinity desensitization-mediated inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs demonstrate clear potential as potent analgesic agents for use in the management of chronic pain associated with heightened P2X3R activation. © The Author(s) 2016.

Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain

PubMed Central

Viatchenko-Karpinski, Viacheslav; Novosolova, Natalia; Ishchenko, Yevheniia; Azhar, M Ameruddin; Wright, Michael; Tsintsadze, Vera; Kamal, Ahmed; Burnashev, Nail; Voitenko, Nana; Giniatullin, Rashid; Lozovaya, Natalia

2016-01-01

Background A growing body of evidence suggests that ATP-gated P2X3 receptors (P2X3Rs) are implicated in chronic pain. We address the possibility that stable, synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons. Results The effects of two stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter, the action of these stable, synthetic Ap4A analogs on inflammatory pain and thermal hyperalgesia is studied through the measurement of antinociceptive effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place mediated by high-affinity desensitization (at low concentrations; IC50 values 100–250 nM) giving way to only weak partial agonism at much higher concentrations (EC50 values ≥ 10 µM). Similar inhibitory activity is observed with human recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root, and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A analogs mediate clear inhibition of pain responses in both in vivo inflammation models. Conclusions Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) being weak partial agonist provoke potent high-affinity desensitization-mediated inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs demonstrate clear potential as potent analgesic agents for use in the management of chronic pain associated with heightened P2X3R activation. PMID:27030723

Enhancement of GABA release through endogenous activation of axonal GABA(A) receptors in juvenile cerebellum.

PubMed

Trigo, Federico F; Chat, Mireille; Marty, Alain

2007-11-14

Recent evidence indicates the presence of presynaptic GABA(A) receptors (GABA(A)Rs) in the axon domain of several classes of central neurons, including cerebellar basket and stellate cells. Here, we investigate the possibility that these receptors could be activated in the absence of electrical or chemical stimulation. We find that low concentrations of GABA increase the frequency of miniature GABAergic synaptic currents. Submaximal concentrations of a GABA(A)R blocker, gabazine, decrease both the miniature current frequency and the probability of evoked GABA release. Zolpidem, an agonist of the benzodiazepine binding site, and NO-711 (1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), a blocker of GABA uptake, both increase the frequency of miniature currents. These effects occur up to postnatal day 14, but not later. Immunohistochemistry indicates the presence of alpha1-containing GABA(A)Rs in interneuron presynaptic terminals with a similar age dependence. We conclude that, under resting conditions, axonal GABA(A)Rs are significantly activated, that this activation results in enhanced GABA release, and that it can be augmented by increasing the affinity of GABA(A)Rs or reducing GABA uptake. Our findings suggest the existence of a positive-feedback mechanism involving presynaptic GABA(A)Rs that maintains a high release rate and a high local GABA concentration in the immature cerebellar network.

A Decision Support Strategy for the Acquisition of CVN Q-Cosal Target Date Material

DTIC Science & Technology

1991-12-01

affecting the parameters are provided by personnel who are familiar with the behavior of the parameters and have access to the data which affect the... COMSUMER LEVEL: E47: (H) @IF(F35ə,0,1) F47: (FO) +E47*@TRIANG(E26,F26,G26)+@TRIANG(EI6,F16,G16) H47: (FO) +F47 A49: ’DELIVERY FROM INTERMEDIATE LEVEL

Aircraft Carrier Operations at Sea: The Challenges of High Reliability Performance

DTIC Science & Technology

1988-07-29

34 Human Communication Research, 4 (Oct.,1978), 283-293. 3. R. A. Cooke and D . M . Rousseau , "The Organizational Culture Inventory : A Quantitative...from USS Carl Vinson (CVN-70) and Air Wing 15. 31 I Endnotes. Section 3. 1. K.H. Roberts and D . M Rousseau , "Research in Nearly Failure Free, High...Weick, School of Business Administration, University of Texas, Austin, Social Psychology and Organizational Behavior; Denise M . Rousseau , Business

Inflation in the Costs of Building Aircraft Carriers

DTIC Science & Technology

2016-04-01

shipbuilding plan for fiscal years 2016 to 2045 in April 2015.1 As detailed in that plan, the Navy intends to purchase six CVN-78 Gerald R. Ford class...labor and materials in the carrier shipbuilding industry. CBO used that interpretation to examine how the Navy did its analysis; other interpretations...expectation that a larger proportion of outlays for shipbuilding in general would be spent in the later years of construction, and thereby would be

Marine Structural Steel Toughness Data Bank (Abridged Edition)

DTIC Science & Technology

1990-08-31

for Table Column Headings: Break? Did specimen fracture completely? CODIc Critical COD CODi Initial COD CVN Energy Charpy V Energy Crack lgth Crack...Standard Y ear ........ .................. * Onen Test Temp KQ CODi CODIc Curve 3l degF ksi*in**0.5 mils mils in-lb/in2 L-T -166...Standard Method .... BS5762 -Standard Year . Test Temp CODIc degC mm -30 0.57 -30 0.68 -30 11.26 (continued) -not reported

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

DTIC Science & Technology

2016-03-08

limited. Yet, it is not too late to examine the carrier’s acquisition history to illustrate the dynamics of shipbuilding—and weapon system—acquisition...rates and the investments needed by the shipbuilder to achieve these efficiencies.31 Later in the hearing, Stackley testified that the history in...for all work packages in accordance with the integrated master schedule;  zero delinquent engineering and planning products;  resolution of

Oscillatory motor network activity during rest and movement: an fNIRS study

PubMed Central

Bajaj, Sahil; Drake, Daniel; Butler, Andrew J.; Dhamala, Mukesh

2014-01-01

Coherent network oscillations (<0.1 Hz) linking distributed brain regions are commonly observed in the brain during both rest and task conditions. What oscillatory network exists and how network oscillations change in connectivity strength, frequency and direction when going from rest to explicit task are topics of recent inquiry. Here, we study network oscillations within the sensorimotor regions of able-bodied individuals using hemodynamic activity as measured by functional near-infrared spectroscopy (fNIRS). Using spectral interdependency methods, we examined how the supplementary motor area (SMA), the left premotor cortex (LPMC) and the left primary motor cortex (LM1) are bound as a network during extended resting state (RS) and between-tasks resting state (btRS), and how the activity of the network changes as participants execute left, right, and bilateral hand (LH, RH, and BH) finger movements. We found: (i) power, coherence and Granger causality (GC) spectra had significant peaks within the frequency band (0.01–0.04 Hz) during RS whereas the peaks shifted to a bit higher frequency range (0.04–0.08 Hz) during btRS and finger movement tasks, (ii) there was significant bidirectional connectivity between all the nodes during RS and unidirectional connectivity from the LM1 to SMA and LM1 to LPMC during btRS, and (iii) the connections from SMA to LM1 and from LPMC to LM1 were significantly modulated in LH, RH, and BH finger movements relative to btRS. The unidirectional connectivity from SMA to LM1 just before the actual task changed to the bidirectional connectivity during LH and BH finger movement. The uni-directionality could be associated with movement suppression and the bi-directionality with preparation, sensorimotor update and controlled execution. These results underscore that fNIRS is an effective tool for monitoring spectral signatures of brain activity, which may serve as an important precursor before monitoring the recovery progress following brain injury. PMID:24550793

Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study.

PubMed

Thamer, Claus; Machann, Jürgen; Stefan, Norbert; Schäfer, Silke A; Machicao, Fausto; Staiger, Harald; Laakso, Markku; Böttcher, Michael; Claussen, Claus; Schick, Fritz; Fritsche, Andreas; Haring, Hans-Ulrich

2008-04-01

We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI). The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI. A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging. With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles. SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes.

Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children.

PubMed

Almeida, Sílvia M; Furtado, José M; Mascarenhas, Paulo; Ferraz, Maria E; Ferreira, José C; Monteiro, Mariana P; Vilanova, Manuel; Ferraz, Fernando P

2018-06-01

Evaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children. What is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children? A cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children. FTO rs9939609 was associated with an increase in body mass index (BMI) and BMI z-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (P< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (P < 0.05). We showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients

PubMed Central

Ruzzo, A; Graziano, F; Galli, Fabio; Galli, Francesca; Rulli, E; Lonardi, S; Ronzoni, M; Massidda, B; Zagonel, V; Pella, N; Mucciarini, C; Labianca, R; Ionta, M T; Bagaloni, I; Veltri, E; Sozzi, P; Barni, S; Ricci, V; Foltran, L; Nicolini, M; Biondi, E; Bramati, A; Turci, D; Lazzarelli, S; Verusio, C; Bergamo, F; Sobrero, A; Frontini, L; Menghi, M; Magnani, M

2017-01-01

Background: Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients’ risk of fluoropyrimidine-related severe toxicity. Methods: The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg’s False Discovery Rate (FDR) procedure was used. Results: FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia. Conclusions: This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy. PMID:29065426

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.

PubMed

Ruzzo, A; Graziano, F; Galli, Fabio; Galli, Francesca; Rulli, E; Lonardi, S; Ronzoni, M; Massidda, B; Zagonel, V; Pella, N; Mucciarini, C; Labianca, R; Ionta, M T; Bagaloni, I; Veltri, E; Sozzi, P; Barni, S; Ricci, V; Foltran, L; Nicolini, M; Biondi, E; Bramati, A; Turci, D; Lazzarelli, S; Verusio, C; Bergamo, F; Sobrero, A; Frontini, L; Menghi, M; Magnani, M

2017-10-24

Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used. FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia. This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.

The Role of Religion and Spirituality in Psychological Distress Prior to Surgery for Urologic Cancer

PubMed Central

Biegler, Kelly; Cohen, Lorenzo; Scott, Shellie; Hitzhusen, Katherine; Parker, Patricia; Gilts, Chelsea D.; Canada, Andrea; Pisters, Louis

2013-01-01

The present study examined the associations between religion and spirituality (R/S), presurgical distress, and other psychosocial factors such as engagement coping, avoidant coping, and social support. Participants were 115 men scheduled for surgery for urologic cancer. Before surgery, participants completed scales measuring intrinsic religiosity, organized religious activity, and nonorganized religious activity (IR, ORA, NORA); social support (Medical Outcomes Study Social Support Survey); and distress (Impact of Event Scale [IES], Perceived Stress Scale [PSS], Brief Symptom Inventory-18 [BSI-18], and Profile of Mood States [POMS]). R/S was positively associated with engagement coping. Social support was positively associated with engagement coping and inversely associated with POMS and PSS scores. Engagement coping was positively associated with IES and BSI scores, and avoidant coping was positively associated with all distress measures. R/S moderated the association between engagement coping and IES scores, such that the association between engagement coping and IES was not significant for men with high R/S scores (greater religious belief). R/S moderated the association between social support and distress; the inverse association between social support and PSS and POMS scores was only significant for men who scored high on R/S. This study replicated findings from previous studies suggesting that engagement and avoidant types of coping can lead to increased distress prior to surgery. Although R/S was associated with engagement coping, it was not associated with any of the distress measures. The finding that R/S moderated the associations between engagement coping and distress and social support and distress suggests that the association between R/S, coping style, social support, and adjustment to stressful life situations is not simplistic, and indirect associations should be explored. PMID:21964511

The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

PubMed

Tousen, Yuko; Matsumoto, Yu; Matsumoto, Chiho; Nishide, Yoriko; Nagahata, Yuya; Kobayashi, Isao; Ishimi, Yoshiko

2016-07-01

Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

Identification, functional characterization and expression patterns of a water-specific aquaporin in the brown dog tick, Rhipicephalus sanguineus.

PubMed

Ball, Andrew; Campbell, Ewan M; Jacob, Jimmy; Hoppler, Stefan; Bowman, Alan S

2009-02-01

Much is known about the physiology of tick salivation, but nothing is known about the movement of water through the cell membranes of salivary glands, a phenomenon usually associated with water channels or aquaporins (AQPs). An AQP, RsAQP1, was identified in a salivary gland cDNA library of Rhipicephalus sanguineus. In the first functional characterization of an acarine AQP, Xenopus oocytes expressing RsAQP1 became water permeable, whereas RsAQP1 did not transport glycerol or urea. RsAQP1 was inhibited by Hg(2+) but not by triethylammonium. Treatment with a protein kinase A activator (cAMP) had no effect on RsAQP1 transport, whereas treatment with a protein kinase C activator (phorbol 12,13-dibutyrate) reduced water flux by 60%. RsAQP1 transcript was present in unfed larvae, nymphs and adult R. sanguineus, but absent in embryos. Partially fed female R. sanguineus expressed RsAQP1 in gut, Malpighian tubules and was particularly abundant in salivary gland tissue, but absent in ovary and synganglion tissues. Because of the importance of water management in tick biology for both the off-host and on-host phases of the life cycle, our findings on tick AQP1 represent a major advancement in our understanding of tick osmoregulation that could potentially be exploited in tick control.

Trans-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at the ANGPTL8 HDL-C GWAS Locus

PubMed Central

Cannon, Maren E.; Duan, Qing; Wu, Ying; Zeynalzadeh, Monica; Xu, Zheng; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Civelek, Mete; Lusis, Aldons J.; Kuusisto, Johanna; Collins, Francis S.; Boehnke, Michael; Tang, Hua; Laakso, Markku; Li, Yun; Mohlke, Karen L.

2017-01-01

Recent genome-wide association studies (GWAS) have identified variants associated with high-density lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8 gene. Given the extensive sharing of GWAS loci across populations, we hypothesized that at least one shared variant at this locus affects HDL-C. The HDL-C–associated variants are coincident with expression quantitative trait loci for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8 expression levels are associated with HDL-C levels. We identified a 400-bp promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to regulating expression in liver and adipose. To identify variants functionally responsible for the HDL-C association, we performed fine-mapping analyses and selected 13 candidate variants that overlap putative regulatory regions to test for allelic differences in regulatory function. Of these variants, rs12463177-G increased transcriptional activity (1.5-fold, P = 0.004) and showed differential protein binding. Six additional variants (rs17699089, rs200788077, rs56322906, rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in transcriptional activity and/or protein binding. Taken together, these data suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue-selective expression and at least one functional variant. PMID:28754724

Functional Characterization of the Osteoarthritis Susceptibility Mapping to CHST11—A Bioinformatics and Molecular Study

PubMed Central

Reynard, Louise N.; Ratnayake, Madhushika; Santibanez-Koref, Mauro

2016-01-01

The single nucleotide polymorphism (SNP) rs835487 is associated with hip osteoarthritis (OA) at the genome-wide significance level and is located within CHST11, which codes for carbohydrate sulfotransferase 11. This enzyme post-translationally modifies proteoglycan prior to its deposition in the cartilage extracellular matrix. Using bioinformatics and experimental analyses, our aims were to characterise the rs835487 association signal and to identify the causal functional variant/s. Database searches revealed that rs835487 resides within a linkage disequilibrium (LD) block of only 2.7 kb and is in LD (r2 ≥ 0.8) with six other SNPs. These are all located within intron 2 of CHST11, in a region that has predicted enhancer activity and which shows a high degree of conservation in primates. Luciferase reporter assays revealed that of the seven SNPs, rs835487 and rs835488, which have a pairwise r2 of 0.962, are the top functional candidates; the haplotype composed of the OA-risk conferring G allele of rs835487 and the corresponding T allele of rs835488 (the G-T haplotype) demonstrated significantly different enhancer activity relative to the haplotype composed of the non-risk A allele of rs835487 and the corresponding C allele of rs835488 (the A-C haplotype) (p < 0.001). Electrophoretic mobility shift assays and supershifts identified several transcription factors that bind more strongly to the risk-conferring G and T alleles of the two SNPs, including SP1, SP3, YY1 and SUB1. CHST11 was found to be upregulated in OA versus non-OA cartilage (p < 0.001) and was expressed dynamically during chondrogenesis. Its expression in adult cartilage did not however correlate with rs835487 genotype. Our data demonstrate that the OA susceptibility is mediated by differential protein binding to the alleles of rs835487 and rs835488, which are located within an enhancer whose target may be CHST11 during chondrogenesis or an alternative gene. PMID:27391021

M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

PubMed

Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

2018-03-06

M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

ηηDiazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca 2+ /calcineurin signalling downstream of GABAA receptors.

PubMed

Nicholson, Martin W; Sweeney, Aaron; Pekle, Eva; Alam, Sabina; Ali, Afia B; Duchen, Michael; Jovanovic, Jasmina N

2018-06-14

Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABA A Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised. Here we report that prolonged exposure to diazepam, the most widely used benzodiazepine in clinic, leads to a gradual disruption of neuronal inhibitory GABAergic synapses. The loss of synapses and the preceding, time- and dose-dependent decrease in surface levels of GABA A Rs, mediated by dynamin-dependent internalisation, were blocked by Ro 15-1788, a competitive benzodiazepine antagonist, and bicuculline, a competitive GABA antagonist, indicating that prolonged enhancement of GABA A R activity by diazepam is integral to the underlying molecular mechanism. Characterisation of this mechanism has revealed a metabotropic-type signalling downstream of GABA A Rs, involving mobilisation of Ca 2+ from the intracellular stores and activation of the Ca 2+ /calmodulin-dependent phosphatase calcineurin, which, in turn, dephosphorylates GABA A Rs and promotes their endocytosis, leading to disassembly of inhibitory synapses. Furthermore, functional coupling between GABA A Rs and Ca 2+ stores was sensitive to phospholipase C (PLC) inhibition by U73122, and regulated by PLCδ, a PLC isoform found in direct association with GABA A Rs. Thus, a PLCδ/Ca 2+ /calcineurin signalling cascade converts the initial enhancement of GABA A Rs by benzodiazepines to a long-term downregulation of GABAergic synapses, this potentially underpinning the development of pharmacological and behavioural tolerance to these widely prescribed drugs.

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.

PubMed

Damiano, Cara R; Aloi, Joseph; Dunlap, Kaitlyn; Burrus, Caley J; Mosner, Maya G; Kozink, Rachel V; McLaurin, Ralph Edward; Mullette-Gillman, O'Dhaniel A; Carter, Ronald McKell; Huettel, Scott A; McClernon, Francis Joseph; Ashley-Koch, Allison; Dichter, Gabriel S

2014-01-31

There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

PubMed Central

Yi, Xingyang; Wang, Yanfen; Zhou, Qiang; Wang, Chun; Cheng, Wen; Chi, Lifen

2016-01-01

Aims: Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation. Methods: A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7 – 10 day treatment. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS). Results: Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS > 2 points) compared with clopidogrel-sensitive patients. Conclusion: CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients. PMID:26961113

A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit*

PubMed Central

Wang, Jingyi; Kuryatov, Alexander; Jin, Zhuang; Norleans, Jack; Kamenecka, Theodore M.; Kenny, Paul J.; Lindstrom, Jon

2015-01-01

Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs but is without effect on α3* or α6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of α4 subunits, which is also a PAM site for steroid hormone estrogens such as 17β-estradiol. Br-PBTC is much more potent than estrogens. Like 17β-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more α4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different α6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two α4 subunits but not those with only one. Three α4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs. PMID:26432642

Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

PubMed

Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

2014-03-01

The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P < 0.05), six significantly downregulated MGMT promoter activity (29-97% decrease; P < 0.05) and one haplotype had no effect. Mechanistic studies conducted support the conclusion that MGMT P/E haplotypes, rather than individual SNPs, differentially regulate MGMT transcription and could thus play a significant role in human sensitivity to environmental and therapeutic alkylating agents.

Senior paediatric specialist registrars' experience in management.

PubMed

Bindal, Taruna; Wall, David; Goodyear, Helen M

2010-06-01

There is an increasing focus on trainees acquiring management skills which form part of college curricula and the guidance provided by the General Medical Council in the UK. To explore the managerial learning activities of senior paediatric specialist registrars (SpRs). Questionnaire study; West Midlands region, UK; senior paediatric SpRs in the last 2 years of training. A 17 item questionnaire was sent by post to all 45 paediatric SpRs in the last 2 years of training. A follow-up email was sent to non-responders. 87% (39/45) SpRs completed a questionnaire. All had participated in clinical managerial activities with 44% (17/39) doing >or=4 h per week. Popular activities were teaching and development of treatment guidelines. Non-clinical managerial experience, mainly rota management and teaching programme organisation, was limited with 64% (25/39) doing

ARG1 Gene Polymorphisms and Their Association in Individuals with Essential Hypertension: A Case-Control Study.

PubMed

Shah, Syed Fawad Ali; Iqbal, Tahir; Qamar, Raheel; Rafiq, Muhammad Arshad; Hussain, Sabir

2018-05-14

The purpose of this study is to investigate the association of variant alleles (rs2781666 and rs2781667) at ARG1 to be involved in the generation of essential hypertension (EH) phenotypes in human subjects. The ARG1 noncoding polymorphisms (rs2781666; Chr6:131572419-G/T and rs2781667; Chr6:131573754-C/T) were investigated in 570 subjects, including 285 individuals diagnosed with EH. Determination of serum arginase activity and concentrations of nitric oxide catabolites were detected by the colorimetric enzymatic assay. Genetic typing of the noncoding polymorphisms, in ARG1, was performed using PCR and restriction digestion strategy. A significant increase in arginase activity was observed in individuals exhibiting EH phenotypes, compared with controls (p < 0.0001). Arginase showed negative correlation with serum nitrite and nitrate (r = -0.446 and r = -0.6075, respectively). A significant difference to be claimed in the distribution of SNPotypes, in rs2781666 and rs2781667, between cases and controls (p = 0.0086 and p = 0.0232; respectively). Interestingly, variant allele T, at both loci, is tightly linked to the disease phenotypes compared to the wild-type allele (p = 0.002; and p = 0.007, respectively). To our knowledge, this report is the first ever that described arginase activity, and the ARG1 polymorphism data of individuals originated in Pakistan, segregating EH phenotypes, thus, highlighting a novel risk factor for the disease.

Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

ERIC Educational Resources Information Center

Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

2015-01-01

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

Workshop on Explosive and Propellant Combustion Mechanisms

DTIC Science & Technology

1991-07-01

Trubert, Decomposition and Combustion Measurements 30 R.S. Miller and A.W. Miziolek, High Energy Density Materials Combustion 56 T.B. Brill...arranging this activity came from Dr. R.S. Miller , Chief Scientist, Mechanics Division, ONR, and Dr. Bernard Finck, Head, New Molecules Section, Defense...34. Armstrong, in consultation with R.S. Miller , J. Boileau, and SNPE colleagues, arranged for the participation of U.S. scientists, especially

Allelic clustering and ancestry-dependent frequencies of rs6232, rs6234, and rs6235 PCSK1 SNPs in a Northern Ontario population sample.

PubMed

Sirois, Francine; Kaefer, Nadine; Currie, Krista A; Chrétien, Michel; Nkongolo, Kabwe K; Mbikay, Majambu

2012-10-01

The PCSK1 (proprotein convertase subtilisin/kexin type 1) locus encodes proprotein convertase 1/3, an endoprotease that converts prohormones and proneuropeptides to their active forms. Spontaneous loss-of-function mutations in the coding sequence of its gene have been linked to obesity in humans. Minor alleles of two common non-synonymous single-nucleotide polymorphisms (SNPs), rs6232 (T > C, N221D) and rs6235 (C > G, S690T), have been associated with increased risk of obesity in European populations. In this study, we compared the frequencies of the rs6232 and rs6234 (G > C, Q665E) SNPs in Aboriginal and Caucasian populations of Northern Ontario. The two SNPs were all relatively less frequent in Aboriginals: The minor allele frequency of the rs6232 SNP was 0.01 in Aboriginals and 0.08 in Caucasians (P < 4.10(-6)); for the rs6234 SNP, it was 0.20 and 0.32, respectively (P < 0.001). Resequencing revealed that the rs6234 SNP variation was tightly linked to that of the rs6235 SNP, as previously reported. Most interestingly, all carriers of the rs6232 SNP variation also carried the rs6234/rs6235 SNP clustered variations, but not the reverse, suggesting the former occurred later on an allele already carrying the latter. These data indicate that, in Northern Ontario Aboriginals, the triple-variant PCSK1 allele is relatively rare and might be of lesser significance for obesity risk in this population.

Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia

PubMed Central

Mondino, Marine; Jardri, Renaud; Suaud-Chagny, Marie-Françoise; Saoud, Mohamed; Poulet, Emmanuel; Brunelin, Jérôme

2016-01-01

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring. PMID:26303936

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.

PubMed

Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

2014-01-01

"Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2

PubMed Central

Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A.; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

2014-01-01

“Schizotypy” is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [123I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum. PMID:25071490

Induction of dendritic spines by β2-containing nicotinic receptors.

PubMed

Lozada, Adrian F; Wang, Xulong; Gounko, Natalia V; Massey, Kerri A; Duan, Jingjing; Liu, Zhaoping; Berg, Darwin K

2012-06-13

Glutamatergic synapses are located mostly on dendritic spines in the adult nervous system. The spines serve as postsynaptic compartments, containing components that mediate and control the synaptic signal. Early in development, when glutamatergic synapses are initially forming, waves of excitatory activity pass through many parts of the nervous system and are driven in part by a class of heteropentameric β2-containing nicotinic acetylcholine receptors (β2*-nAChRs). These β2*-nAChRs are widely distributed and, when activated, can depolarize the membrane and elevate intracellular calcium levels in neurons. We show here that β2*-nAChRs are essential for acquisition of normal numbers of dendritic spines during development. Mice constitutively lacking the β2-nAChR gene have fewer dendritic spines than do age-matched wild-type mice at all times examined. Activation of β2*-nAChRs by nicotine either in vivo or in organotypic slice culture quickly elevates the number of spines. RNA interference studies both in vivo and in organotypic culture demonstrate that the β2*-nAChRs act in a cell-autonomous manner to increase the number of spines. The increase depends on intracellular calcium and activation of calcium, calmodulin-dependent protein kinase II. Absence of β2*-nAChRs in vivo causes a disproportionate number of glutamatergic synapses to be localized on dendritic shafts, rather than on spines as occurs in wild type. This shift in synapse location is found both in the hippocampus and cortex, indicating the breadth of the effect. Because spine synapses differ from shaft synapses in their signaling capabilities, the shift observed is likely to have significant consequences for network function.

The sigma-1 receptor: roles in neuronal plasticity and disease

PubMed Central

Kourrich, Saïd; Su, Tsung-Ping; Fujimoto, Michiko; Bonci, Antonello

2012-01-01

Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. The Sig-1R is an intracellular chaperone that resides specifically at the endoplasmic reticulum (ER)-mitochondrion interface referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER-mitochondrion Ca2+ signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanism linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating some aspects of neurological and psychiatric diseases. PMID:23102998

Characteristics of the Remote Sensing Data Used in the Proposed Unfccc REDD+ Forest Reference Emission Levels (frels)

NASA Astrophysics Data System (ADS)

Johnson, B. A.; Scheyvens, H.; Samejima, H.; Onoda, M.

2016-06-01

Developing countries must submit forest reference emission levels (FRELs) to the UNFCCC to receive incentives for REDD+ activities (e.g. reducing emissions from deforestation/forest degradation, sustainable management of forests, forest carbon stock conservation/enhancement). These FRELs are generated based on historical CO2 emissions in the land use, land use change, and forestry sector, and are derived using remote sensing (RS) data and in-situ forest carbon measurements. Since the quality of the historical emissions estimates is affected by the quality and quantity of the RS data used, in this study we calculated five metrics (i-v below) to assess the quality and quantity of the data that has been used thus far. Countries could focus on improving on one or more of these metrics for the submission of future FRELs. Some of our main findings were: (i) the median percentage of each country mapped was 100%, (ii) the median historical timeframe for which RS data was used was 11.5 years, (iii) the median interval of forest map updates was 4.5 years, (iv) the median spatial resolution of the RS data was 30m, and (v) the median number of REDD+ activities that RS data was used for operational monitoring of was 1 (typically deforestation). Many new sources of RS data have become available in recent years, so complementary or alternative RS data sets for generating future FRELs can potentially be identified based on our findings; e.g. alternative RS data sets could be considered if they have similar or higher quality/quantity than the currently-used data sets.

[Associations between chronotype, road accidents and polymorphisms in genes linked with biological clock and dopaminergic system].

PubMed

Taranov, A O; Puchkova, A N; Slominsky, P A; Tupitsyna, T V; Dementiyenko, V V; Dorokhov, V B

2017-01-01

Public transport driving is a highly demanding activity requiring high skills and responsibility. Shift work, problems with regular sleep schedule negatively impact psychomotor reactions, cognitive functions and ability to react appropriately to the changing environment. For professional drivers all these factors may lead to the increased risk of a road accident. Individual differences in chronotype, cognitive and emotional control are partially genetically determined. Our study aimed to investigate the possible associations between chronotype parameters, traffic accident history and single nucleotide polymorphisms (SNPs) in a number of genes: RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1 (rs324981), NPAS2 (rs4851377), DRD3 (rs6280), SLC6A3 (rs6347), DBH (rs1611125). We have studied 303 professional bus drivers working on rolling shifts in the Moscow region who had a recorded history of road accidents. The studied group was genotyped on selected SNPs and has filled out two chronotype questionnaires: MCTQ and shortened SWPAQ (Putilov A.A, 2014). A mixed chronotype with high levels of morning and evening alertness prevailed in the group. A prominent social jetlag caused by shift work was found. For SNP in PER3 gene there was an association with morning activation. SNP in CLOCK gene was associated with social jetlag and the risk to cause a crash. Minor alleles of SNPs in NPSR1and SLC6A3 correlated with later chronotype and increased risk of a road accident. We suppose that these polymorphisms may be amongst the genetic factors connecting chronotype and road accident risk.

Crystal structures of apo wild-type M. jannaschii tyrosyl-tRNA synthetase (TyrRS) and an engineered TyrRS specific for O-methyl-L-tyrosine

PubMed Central

Zhang, Yan; Wang, Lei; Schultz, Peter G.; Wilson, Ian A.

2005-01-01

The Methanococcus jannaschii tRNATyr/TyrRS pair has been engineered to incorporate unnatural amino acids into proteins in E. coli. To reveal the structural basis for the altered specificity of mutant TyrRS for O-methyl-l-tyrosine (OMeTyr), the crystal structures for the apo wild-type and mutant M. jannaschii TyrRS were determined at 2.66 and 3.0 Å, respectively, for comparison with the published structure of TyrRS complexed with tRNATyr and substrate tyrosine. A large conformational change was found for the anticodon recognition loop 257–263 of wild-type TyrRS upon tRNA binding in order to facilitate recognition of G34 of the anticodon loop through π-stacking and hydrogen bonding interactions. Loop 133–143, which is close to the tRNA acceptor stem-binding site, also appears to be stabilized by interaction with the tRNATyr. Binding of the substrate tyrosine results in subtle and cooperative movements of the side chains within the tyrosine-binding pocket. In the OMeTyr-specific mutant synthetase structure, the signature motif KMSKS loop and acceptor stem-binding loop 133–143 were surprisingly ordered in the absence of bound ATP and tRNA. The active-site mutations result in altered hydrogen bonding and steric interactions which favor binding of OMeTyr over l-tyrosine. The structure of the mutant and wild-type TyrRS now provide a basis for generating new active-site libraries to evolve synthetases specific for other unnatural amino acids. PMID:15840835

Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

PubMed

Stefanescu, Roxana A; Shore, Susan E

2017-03-01

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N -methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology. Copyright © 2017 the American Physiological Society.

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 propellant load. The results of the RS-34 Phoenix Concept Study show that the system is technically sufficient to successfully support all of the missions to rendezvous, capture, and de-orbit targets including Envisat and Hubble Space Telescope. The results and benefits of the RS-34 Orbital Debris Application Concept Study are presented in this paper.

"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density".

PubMed

Piedra, María; García-Unzueta, María T; Berja, Ana; Paule, Blanca; Lavín, Bernardo A; Valero, Carmen; Riancho, José A; Amado, José A

2011-12-20

Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT. We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied. Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA). Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.

Medical Education in Infectious Diseases. Using Smartphone Apps for Active Learning

PubMed Central

Valdez, Luis; Gray, Andrea; Ramos, Gaston; Siu, Hugo

2017-01-01

Abstract Background Active Learning using smartphone technology can be implemented as a tool for teaching medical students (MS) and residents (Rs). The use of technology would increase participation and enhance student learning by engaging them in solving ID clinical case scenarios. Our objective was to describe the methods used and to share the opinions of the users of such active learning methods. Methods The smartphone applications used were Socrative and WhatsApp. We used Socrative during the Universidad Peruana de Ciencias Aplicadas (UPC) ID course for MS in two different ways. In selected lectures (4 of 32), teacher paced questions were asked based on clinical scenarios related to the topic reviewed, and by voluntary homework questionnaires (student paced). At the British American Hospital (BAH) Medicine Department (MS and Rs) Socrative was used similarly: during some noon lectures (teacher paced questions) and during the baseline MS exam and Rs mid-year exam and voluntary homework questions (student paced). WhatsApp is currently used at the BAH with questions send from Monday to Friday. MS /Rs answer individually via WhatsApp to the mentor in charge. The right answer is given the next day. Questions using WhatsApp deal with recent cases seen at the Wards or in the outpatient clinic, and are designed so that the MS/Rs must do quick literature searches in order to provide the right answer. Results Forty-one MS/Rs answered the survey on Socrative use, 25 of 48 (52%) of UPC MS and 16 (89%) MS/Rs from the BAH. Forty (97%) believed using Socrative had influenced their learning and all but 2 believed it promoted participation from the class. 36 (87.8%) would like to have Socrative used in other lectures and 35 (85%) in other courses. Only one person voted against Socrative use in courses or lectures. With regards to WhatsApp use 16 MS/Rs from BAH answered the survey. Six had used before WhatsApp as a teaching tool. All felt the methodology was useful for learning and promoting reading and would recommend this methodology to promote learning on a student paced way. Conclusion Socrative and WhatsApp can be used for teaching ID through MS/Rs smartphones. Most MS/Rs who were surveyed recommended the use of such methods in their education. Disclosures All authors: No reported disclosures.

The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population.

PubMed

Mihaljevic, Marina; Zeljic, Katarina; Soldatovic, Ivan; Andric, Sanja; Mirjanic, Tijana; Richards, Alexander; Mantripragada, Kiran; Pekmezovic, Tatjana; Novakovic, Ivana; Maric, Nadja P

2017-09-01

Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability-stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the case-sibling-control design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC "risk" haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophrenia.

Genetic contribution of CISH promoter polymorphisms to susceptibility to tuberculosis in Chinese children.

PubMed

Sun, Lin; Jin, Ya-qiong; Shen, Chen; Qi, Hui; Chu, Ping; Yin, Qing-qin; Li, Jie-qiong; Tian, Jian-ling; Jiao, Wei-wei; Xiao, Jing; Shen, A-dong

2014-01-01

Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide, particularly in developing countries. A series of candidate genes have been suggested to be associated with development of TB disease. Among them, the human Cytokine-inducible Src homology 2(SH2) domain protein (CISH) gene has been very recently reported to be involved in T cell activation and differentiation in response to Mycobacterium tuberculosis infection. Here, we studied the association between CISH promoter polymorphisms and pediatric TB. A case-control study enrolled 352 TB patients and 527 healthy controls, who were of Han Chinese ethnicity and aged from 0.2 to 18 years. CISH gene promoter SNPs rs414171, rs622502 and rs809451 were genotyped in all subjects and transcriptional activity, mRNA level, and plasma cytokine level of subjects with different genotypes were further examined. Carriers with rs414171TT homozygotes and rs809451GC heterozygotes had a 1.78-fold (95% CI,1.16-2.74) and 1.86-fold (95% CI, 1.26-2.74) excess risk of developing TB compared to those with wild-type genotypes. A greater risk of TB disease was observed in population carrying C(-809451)-T(-414171)-C(-622502) haplotype (OR 3.66, 95% CI:2.12-6.32). The G(-809451)-A(-414171)-C(-622502)-containing CISH promoter drove a 5.43-fold increased reporter expression compared to the C(-809451)-T(-414171)-C(-622502)-containing counterpart in Hela cell lines (P = 0.0009). PBMCs carrying rs414171TT homozygotes and rs809451GC heterozygotes showed a reduced CISH mRNA level compared to cells carrying wild type genotypes. Individuals with the rs414171TT genotype had significantly increased IL-12p40 and IL-10 production. In conclusion, CISH promoter rs414171 and rs809451 polymorphisms may play a vital role in mediating individual susceptibility to tuberculosis.

Obesity, physical activity and prediabetes in adult children of people with diabetes.

PubMed

Compeán-Ortiz, Lidia G; Trujillo-Olivera, Laura Elena; Valles-Medina, Ana María; Reséndiz-González, Eunice; García-Solano, Beatriz; Pérez, Beatriz Del Angel

2018-01-08

Determine prevalence of obesity / overweight, physical activity (PA) and prediabetes in adult children of parents with type 2 diabetes; identify differences according to sociodemographic variables, and describe the relationship of obesity/overweight with fasting glucose (FG) and glycosylated hemoglobin (A1C). Cross-sectional study in 30 Mexican families with 53 participating adult children. Obesity / overweight was determined with Body Mass Index (BMI), Waist Circumference (WC) and body fat percentage (BFP); PA with the short International Physical Activity Questionnaire (IPAQ), and prediabetes with FG. 64% of participants presented obesity / overweight, 32% low PA, and 19% prediabetes. Men had higher WC than women (U= 219, p= 0.03). Women showed more BFP than men (U= 142, p <0.01). Blood glucose was related to BFP (rs= 0.336, p < 0.05), the A1C with the BMI (rs= 0.417, p <0.01), WC (rs= 0.394, p<0.01), BFP (rs= 0.494, p<0.01) and intense PA (rs= - 0.285, p<0.05). High prevalence of obesity / overweight and low PA were found. The FG was related only to BFP and A1C, in addition to BMI, WC and inversely with intense BP. It is recommended to modify the educational strategies of nursing at a family level.

Obesity, physical activity and prediabetes in adult children of people with diabetes 1

PubMed Central

Compeán-Ortiz, Lidia G.; Trujillo-Olivera, Laura Elena; Valles-Medina, Ana María; Reséndiz-González, Eunice; García-Solano, Beatriz; Pérez, Beatriz Del Angel

2018-01-01

ABSTRACT Objectives: Determine prevalence of obesity / overweight, physical activity (PA) and prediabetes in adult children of parents with type 2 diabetes; identify differences according to sociodemographic variables, and describe the relationship of obesity/overweight with fasting glucose (FG) and glycosylated hemoglobin (A1C). Methods: Cross-sectional study in 30 Mexican families with 53 participating adult children. Obesity / overweight was determined with Body Mass Index (BMI), Waist Circumference (WC) and body fat percentage (BFP); PA with the short International Physical Activity Questionnaire (IPAQ), and prediabetes with FG. Results: 64% of participants presented obesity / overweight, 32% low PA, and 19% prediabetes. Men had higher WC than women (U= 219, p= 0.03). Women showed more BFP than men (U= 142, p <0.01). Blood glucose was related to BFP (rs= 0.336, p < 0.05), the A1C with the BMI (rs= 0.417, p <0.01), WC (rs= 0.394, p<0.01), BFP (rs= 0.494, p<0.01) and intense PA (rs= - 0.285, p<0.05). Conclusions: High prevalence of obesity / overweight and low PA were found. The FG was related only to BFP and A1C, in addition to BMI, WC and inversely with intense BP. It is recommended to modify the educational strategies of nursing at a family level. PMID:29319746

Submerged Culture of Grifola gargal and G. sordulenta (Higher Basidiomycetes) from Argentina as a Source of Mycelia with Antioxidant Activity.

PubMed

Postemsky, Pablo Daniel; Curvetto, Néstor Raúl

2015-01-01

Submerged culture is an alternative mycelium source for Grifola gargal and G. sordulenta, two rare edible mushrooms related to Grifola frondosa. This work studies their mycelia as a source of antioxidants. The efficient concentrations of methanolic extracts in both radical scavenging (RS) and reducing power (RP) abilities in G. gargal and in G. sordulenta showed a high antioxidant activity. In the experimental design used, the antioxidant activity mainly depended on the culture conditions rather than on the media composition. Irrespective of the basal culture medium, mycelium methanolic extracts of G. sordulenta obtained from culture in Erlenmeyer flasks showed equivalents to ascorbic acid (EQ(AA)) RS-EQ(AA) and RP-EQ(AA) contents higher than the corresponding values obtained with jar cultures. Under stationary cultivation, G. sordulenta produced approximately 50% higher content in both RS-EQ(AA) and RP-EQ(AA) than the medicinal mushroom G. frondosa. Phenolics correlated with RS-EQ(AA) and RP-EQ(AA) in G. gargal and with RP-EQ(AA) in G. sordulenta; besides, thin-layer chromatography showed these compounds to be at least in part related to the RS capacity. It is concluded that G. gargal and G. sordulenta mycelia are excellent sources of antioxidant metabolites.

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

PubMed

Law, Philip J; Berndt, Sonja I; Speedy, Helen E; Camp, Nicola J; Sava, Georgina P; Skibola, Christine F; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R; Clot, Guillem; Teras, Lauren R; Quintela, Inés; Birmann, Brenda M; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R; Hall, Andrew G; Purdue, Mark P; Mainou-Fowler, Tryfonia; Vajdic, Claire M; Jackson, Graham H; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G; Lawrence, Charles; Call, Timothy G; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K; Conde, Lucia; Bracci, Paige M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C H; Southey, Melissa C; Milne, Roger L; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M; Harris, Robert J; Miligi, Lucia; Pettitt, Andrew R; North, Kari E; Allsup, David J; Fraumeni, Joseph F; Bailey, James R; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J S; Catovsky, Daniel; Campo, Elias; Cerhan, James R; Allan, James M; Rothman, Nathanial; Houlston, Richard; Slager, Susan

2017-02-06

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10 -13 ), 1q42.13 (rs41271473, P=1.06 × 10 -10 ), 4q24 (rs71597109, P=1.37 × 10 -10 ), 4q35.1 (rs57214277, P=3.69 × 10 -8 ), 6p21.31 (rs3800461, P=1.97 × 10 -8 ), 11q23.2 (rs61904987, P=2.64 × 10 -11 ), 18q21.1 (rs1036935, P=3.27 × 10 -8 ), 19p13.3 (rs7254272, P=4.67 × 10 -8 ) and 22q13.33 (rs140522, P=2.70 × 10 -9 ). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1-dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

PubMed

Dries, Eef; Santiago, Demetrio J; Johnson, Daniel M; Gilbert, Guillaume; Holemans, Patricia; Korte, Sanne M; Roderick, H Llewelyn; Sipido, Karin R

2016-10-15

The dyadic cleft, where coupled ryanodine receptors (RyRs) reside, is thought to serve as a microdomain for local signalling, as supported by distinct modulation of coupled RyRs dependent on Ca 2+ /calmodulin-dependent kinase II (CaMKII) activation during high-frequency stimulation. Sympathetic stimulation through β-adrenergic receptors activates an integrated signalling cascade, enhancing Ca 2+ cycling and is at least partially mediated through CaMKII. Here we report that CaMKII activation during β-adrenergic signalling is restricted to the dyadic cleft, where it enhances activity of coupled RyRs thereby contributing to the increase in diastolic events. Nitric oxide synthase 1 equally participates in the local modulation of coupled RyRs. In contrast, the increase in the Ca 2+ content of the sarcoplasmic reticulum and related increase in the amplitude of the Ca 2+ transient are primarily protein kinase A-dependent. The present data extend the concept of microdomain signalling in the dyadic cleft and give perspectives for selective modulation of RyR subpopulations and diastolic events. In cardiac myocytes, β-adrenergic stimulation enhances Ca 2+ cycling through an integrated signalling cascade modulating L-type Ca 2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca 2+ /calmodulin-dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca 2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca 2+ ] i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca 2+ sparks, which are assigned to coupled and non-coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca 2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces spark frequency in coupled RyRs only; NOS1 inhibition mimics the effect of CaMKII inhibition. Moreover, ISO induces the repetitive activation of coupled RyR clusters through CaMKII activation. Immunostaining shows high levels of CaMKII phosphorylation at the dyadic cleft. CaMKII inhibition reduces I CaL and local Ca 2+ transients during depolarizing steps but has only modest effects on amplitude or relaxation of the global Ca 2+ transient. In contrast, protein kinase A (PKA) inhibition reduces spark frequency in all RyRs concurrently with a reduction of sarcoplasmic reticulum Ca 2+ content, Ca 2+ transient amplitude and relaxation. In conclusion, CaMKII activation during β-adrenergic stimulation is restricted to the dyadic cleft microdomain, enhancing LTCC-triggered local Ca 2+ release as well as spontaneous diastolic Ca 2+ release whilst PKA is the major pathway increasing global Ca 2+ cycling. Selective CaMKII inhibition may reduce potentially arrhythmogenic release without negative inotropy. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

An Association Study on IL16 Gene Polymorphisms with the Risk of Sporadic Alzheimer's Disease

PubMed Central

Khoshbakht, Tayyebeh; Soosanabadi, Mohsen; Neishaboury, Maryam; Kamali, Koorosh; Karimlou, Masoud; Bazazzadegan, Nilofar; Khorram Khorshid, Hamid Reza

2015-01-01

Background: Interleukin-16 (IL-16) is an important regulator of T cell activation and was reported to act as a chemoattractant agent. There are evidences that IL16 can control the neuroinflammatory processes in Alzheimer's Disease (AD). This study was performed to investigate the role or association of IL16 polymorphisms, rs11556218 and rs4778889 with the risk of late-onset Alzheimer's disease (LOAD) in Iranian population. Methods: Totally, 148 AD patients and 137 nondemented and age-matched subjects were recruited in this study. Genotyping of rs11556218 T/G and rs4778889 T/C polymorphisms was performed by PCR-RFLP method using the NdeI and AhdI restriction enzymes, respectively. Results: Statistical analysis of rs11556218 genotypes showed a protective effect against AD in the heterozygote genotype (p=0.001, OR=0.16) as well as rs4778889 (p=0.001, OR=0.23). Frequency of rs11556218 allele T was higher in controls than patients (p=0.001, OR=0.32). However, there was no significant difference in the frequencies of rs4778889 alleles between the AD patients and controls. Conclusion: Our results indicate that the rs11556218 and rs4778889 polymorphisms have a protective role in the development of sporadic AD in Iranian population. PMID:26306153

Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women1

PubMed Central

Mao, Jinyuan; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher WG; Ahmadi, Kourosh R; Rayman, Margaret P

2016-01-01

Background: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]. Objective: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 μg/d. Design: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation. Results: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579. Conclusions: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591. PMID:26675765

Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy.

PubMed

Peng, Ling-Ling; Zhao, Yuan-Qi; Zhou, Zi-Yi; Jin, Jing; Zhao, Min; Chen, Xin-Meng; Chen, Ling-Yan; Cai, Ye-Feng; Li, Jia-Li; Huang, Min

2016-11-01

Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A 2 receptor (TXA 2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A 2 (Lp-PLA 2 , encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB 2 ELISA kit. Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.

Activation of postsynaptic GABAB receptors modulates the bursting pattern and synaptic activity of olfactory bulb juxtaglomerular neurons.

PubMed

Karpuk, Nikolay; Hayar, Abdallah

2008-01-01

Olfactory bulb glomeruli are formed by a network of three major types of neurons collectively called juxtaglomerular (JG) cells, which include external tufted (ET), periglomerular (PG), and short axon (SA) cells. There is solid evidence that gamma-aminobutyric acid (GABA) released from PG neurons presynaptically inhibits glutamate release from olfactory nerve terminals via activation of GABA(B) receptors (GABA(B)-Rs). However, it is still unclear whether ET cells have GABA(B)-Rs. We have investigated whether ET cells have functional postsynaptic GABA(B)-Rs using extracellular and whole cell recordings in olfactory bulb slices. In the presence of fast synaptic blockers (CNQX, APV, and gabazine), the GABA(B)-R agonist baclofen either completely inhibited the bursting or reduced the bursting frequency and increased the burst duration and the number of spikes/burst in ET cells. In the presence of fast synaptic blockers and tetrodotoxin, baclofen induced an outward current in ET cells, suggesting a direct postsynaptic effect. Baclofen reduced the frequency and amplitude of spontaneous EPSCs in PG and SA cells. In the presence of sodium and potassium channel blockers, baclofen reduced the frequency of miniature EPSCs, which were inhibited by the calcium channel blocker cadmium. All baclofen effects were reversed by application of the GABA(B)-R antagonist CGP55845. We suggest that activation of GABA(B)-Rs directly inhibits ET cell bursting and decreases excitatory dendrodendritic transmission from ET to PG and SA cells. Thus the postsynaptic GABA(B)-Rs on ET cells may play an important role in shaping the activation pattern of the glomeruli during olfactory coding.

Expression of nattokinase in Escherichia coli and renaturation of its inclusion body.

PubMed

Ni, He; Guo, Peng-Cheng; Jiang, Wei-Ling; Fan, Xiao-Min; Luo, Xiang-Yu; Li, Hai-Hang

2016-08-10

Nattokinase is an important fibrinolytic enzyme with therapeutic applications for cardiovascular diseases. The full-length and mature nattokinase genes were cloned from Bacillus subtilis var. natto and expressed in pQE30 vector in Escherichia coli. The full-length gene expressed low nattokinase activity in the intracellular soluble and the medium fractions. The mature gene expressed low soluble nattokinase activity and large amount insoluble protein in inclusion bodies without enzyme activity. Large amount of refolding solutions (RSs) at different pH values were screening and RS-10 and RS-11 at pH 9 were selected to refold nattokinase inclusion bodies. The recombinant cells were lysed with 0.1mg/mL lysozyme and ultrasonic treatment. After centrifugation, the pellete was washed twice with 20mM Tris-HCl buffer (pH 7.5) containing 1% Triton X-100 to purify the inclusion bodies. The inclusion bodies were dissolved in water at pH 12.0 and refolded with RS-10. The refolded proteins showed 42.8IU/mg and 79.3IU/mg fibrinolytic activity by the traditional dilution method (20-fold dilution into RS-10) and the directly mixing the protein solution with equal volume RS-10, respectively, compared to the 52.0IU/mg of total water-soluble proteins from B. subtilis var. natto. This work demonstrated that the inclusion body of recombinant nattokinase expressed in E. coli could be simply refolded to the natural enzyme activity level by directly mixing the protein solution with equal volume refolding solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons.

PubMed

Qi, Mengwen; Wu, Chunfeng; Wang, Zhouqing; Zhou, Li; Men, Chen; Du, Yimei; Huang, Songming; Chen, Lei; Chen, Ling

2018-01-01

Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission. © 2018 The Author(s). Published by S. Karger AG, Basel.

Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

PubMed

Delwing-de Lima, Daniela; Fröhlich, Monique; Dalmedico, Leticia; Aurélio, Juliana Gruenwaldt Maia; Delwing-Dal Magro, Débora; Pereira, Eduardo Manoel; Wyse, Angela T S

2017-04-01

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Transporter TAP1-637G and Immunoproteasome PSMB9-60H Variants Influence the Risk of Developing Vitiligo in the Saudi Population

PubMed Central

Elhawary, Nasser Attia; Bogari, Neda; Jiffri, Essam Hussien; Rashad, Mona; Fatani, Abdulhamid; Tayeb, Mohammed

2014-01-01

We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks (P < 0.0001 and P = 0.007, resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles. PMID:25548428

Pretreatment with β-adrenergic receptor agonists facilitates induction of LTP and sharp wave ripple complexes in rodent hippocampus.

PubMed

Ul Haq, Rizwan; Anderson, Marlene; Liotta, Agustin; Shafiq, Maria; Sherkheli, Muhammad Azhar; Heinemann, Uwe

2016-12-01

Norepinephrine, is involved in the enhancement of learning and memory formation by regulating synaptic mechanisms through its ability to activate pre- and post-synaptic adrenergic receptors. Here we show that β-agonists of norepinephrine facilitate the induction of both associational LTP and sharp wave ripples (SPW-Rs) in acute slices of rat hippocampus in area CA3. Surprisingly, this facilitating effect persists when slices are only pretreated with β-receptor agonists followed by wash out and application of the unspecific β-adrenoreceptor (βAR) antagonist propranolol. During application of βAR agonists repeated stimulation resulted in facilitated induction of SPW-Rs. Since SPW-Rs are thought to be involved in memory replay we studied the effects of βAR-agonists on spontaneous SPW-Rs in murine hippocampus and found that amplitude and incidence of SPW-Rs increased. These effects involve cyclic-AMP and the activation of protein kinase A and suggest a supportive role in memory consolidation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Antioxidant effect of poleo and oregano essential oil on roasted sunflower seeds.

PubMed

Quiroga, Patricia R; Grosso, Nelson R; Nepote, Valeria

2013-12-01

The objective was to evaluate the stability of sensory and chemical parameters in roasted sunflower seeds supplemented with oregano and poleo essential oils; and the consumer acceptability of this product. Four samples were prepared: plain roasted sunflower seeds (Control = RS-C), and sunflower seeds added with oregano (RS-O) or poleo (RS-P) essential oils or BHT (RS-BHT). Consumer acceptance was determined on fresh samples. The overall acceptance averages were 6.13 for RS-C, 5.62 for RS-P, and 5.50 for RS-O (9-point hedonic scale). The addition of BHT showed greater protection against the oxidation process in the roasted sunflower seeds. Oregano essential oil exhibited a greater antioxidant effect during storage than poleo essential oil. Both essential oils (oregano and poleo) provided protection to the product, inhibiting the formation of undesirable flavors (oxidized and cardboard). The antioxidant activity that presents essential oils of oregano and poleo could be used to preserve roasted sunflower seeds. © 2013 Institute of Food Technologists®

Axonal GABAA receptors.

PubMed

Trigo, Federico F; Marty, Alain; Stell, Brandon M

2008-09-01

Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

Muscarinic Acetylcholine Receptor Localization and Activation Effects on Ganglion Response Properties

PubMed Central

Renna, Jordan M.; Amthor, Franklin R.; Keyser, Kent T.

2010-01-01

Purpose. The activation and blockade of muscarinic acetylcholine receptors (mAChRs) affects retinal ganglion cell light responses and firing rates. This study was undertaken to identify the full complement of mAChRs expressed in the rabbit retina and to assess mAChR distribution and the functional effects of mAChR activation and blockade on retinal response properties. Methods. RT-PCR, Western blot analysis, and immunohistochemistry were used to identify the complement and distribution of mAChRs in the rabbit retina. Extracellular electrophysiology was used to determine the effects of the activation or blockade of mAChRs on ganglion cell response properties. Results. RT-PCR of whole neural retina resulted in the amplification of mRNA transcripts for the m1 to m5 mAChR subtypes. Western blot and immunohistochemical analyses confirmed that all five mAChR subtypes were expressed by subpopulations of bipolar, amacrine, and ganglion cells in the rabbit retina, including subsets of cells in cholinergic and glycinergic circuits. Nonspecific muscarinic activation and blockade resulted in the class-specific modulation of maintained ganglion cell firing rates and light responses. Conclusions. The expression of mAChR subtypes on subsets of bipolar, amacrine, and ganglion cells provides a substrate for both enhancement and suppression of retinal responses via activation by cholinergic agents. Thus, the muscarinic cholinergic system in the retina may contribute to the modulation of complex stimuli. Understanding the distribution and function of mAChRs in the retina has the potential to provide important insights into the visual changes that are caused by decreased ACh in the retinas of Alzheimer's patients and the potential visual effects of anticholinergic treatments for ocular diseases. PMID:20042645

Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

PubMed

Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

2016-08-01

The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

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…

Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.; Zheng, Yun-Min; Levin, Robert; Wang, Yong-Xiao

2016-01-01

ABSTRACT Contraction and relaxation of urinary bladder smooth muscle cells (UBSMCs) represent the important physiological functions of the bladder. Contractile responses in UBSMCs are regulated by a number of ion channels including big-conductance Ca2+- activated K+ (BK) channels. Great progress has been made in studies of BK channels in UBSMCs. The intent of this review is to summarize recent exciting findings with respect to the functional interactions of BK channels with muscarinic receptors, ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs) as well as their functional importance under normal and pathophysiological conditions. BK channels are highly expressed in UBSMCs. Activation of muscarinic M3 receptors inhibits the BK channel activity, facilitates opening of voltage-dependent Ca2+ (CaV) channels, and thereby enhances excitability and contractility of UBSMCs. Signaling molecules and regulatory mechanisms involving RyRs and IP3Rs have a significant effect on functions of BK channels and thereby regulate cellular responses in UBSMCs under normal and pathophysiological conditions including overactive bladders. Moreover, BK channels may represent a novel target for the treatment of bladder dysfunctions. PMID:27101440

Association of Common Genetic Variants in the MAP4K4 Locus with Prediabetic Traits in Humans

PubMed Central

Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Guilherme, Adilson; Grallert, Harald; Schulze, Matthias B.; Boeing, Heiner; Stefan, Norbert; Fritsche, Andreas; Czech, Michael P.; Häring, Hans-Ulrich

2012-01-01

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is expressed in all diabetes-relevant tissues and mediates cytokine-induced insulin resistance. We investigated whether common single nucleotide polymorphisms (SNPs) in the MAP4K4 locus associate with glucose intolerance, insulin resistance, impaired insulin release, or elevated plasma cytokines. The best hit was tested for association with type 2 diabetes. Subjects (N = 1,769) were recruited from the Tübingen Family (TÜF) study for type 2 diabetes and genotyped for tagging SNPs. In a subgroup, cytokines were measured. Association with type 2 diabetes was tested in a prospective case-cohort study (N = 2,971) derived from the EPIC-Potsdam study. Three SNPs (rs6543087, rs17801985, rs1003376) revealed nominal and two SNPs (rs11674694, rs11678405) significant associations with 2-hour glucose levels. SNPs rs6543087 and rs11674694 were also nominally associated with decreased insulin sensitivity. Another two SNPs (rs2236936, rs2236935) showed associations with reduced insulin release, driven by effects in lean subjects only. Three SNPs (rs11674694, rs13003883, rs2236936) revealed nominal associations with IL-6 levels. SNP rs11674694 was significantly associated with type 2 diabetes. In conclusion, common variation in MAP4K4 is associated with insulin resistance and β-cell dysfunction, possibly via this gene’s role in inflammatory signalling. This variation’s impact on insulin sensitivity may be more important since its effect on insulin release vanishes with increasing BMI. PMID:23094072

Mechanical Properties and Seawater Behavior of Nitronic 50 (22Cr-13Ni- 5Mn) Plate

DTIC Science & Technology

1976-01-01

Bal - balance misc - miscellaneous cfh - cubic feet per hour mpy - mils per year c/m - cycles per minute my - millivolts CVN - Charpy V-notch No...High-Cycle Fatigue Specimens F_gure 6 - Drawings; Low-Cycle Fatigue Specimens Figure 7 - Curve; Charpy V-Notch Impact Toughness Versus Temperature...for Nitronic 50 Base Plate FiGure 8 - Curve; Charpy V-Notch Toughness Versus Tempera- ture for Nitrcnic 50 Weldments Figure 9 - Photographs; Fracture

An Argument for Consolidation: The ANZUS Carrier Task Force

DTIC Science & Technology

2012-06-05

the USN, assisting U.S. and NATO forces in Operation SLIPPER 18 by providing MSO (including counter piracy and counter-terrorism) as part of the...continues to be a key foreign policy objective of AUS.” 33 At AUSMIN 2010 (AUS-US Ministerial Consultations), the principal forum for bilateral...force tailored specifically to meet the concerns of the IP at a shared price and draw up a force-structure framework. In addition to the CVN, a

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

DTIC Science & Technology

2010-04-01

Aircraft Carrier Homeporting In Mayport,” available online at http://www.defenselink.mil/releases/release.aspx?releaseid= 12600. 4 Department of Defense...miles is the straight-line distance between the two locations, as calculated by the “How Fair Is It?” online distance calculator available at http...Fair Is It?” online distance calculator available at http://www.indo.com/cgi-bin/dist. 13 Department of the Navy, Report on Strategic Plan for

The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells.

PubMed

Lee, Yu-Nee; Nechushtan, Hovav; Figov, Navah; Razin, Ehud

2004-02-01

The involvement of microphthalmia transcription factor (MITF) in the function of mast cells, melanocytes, and osteoclasts has recently started to be investigated in depth. In a previous study, we found Hint to be associated with MITF in mast cells and showed that it suppresses MITF's transcriptional activity. Here, we have found that lysyl-tRNA synthetase (LysRS) is also associated with MITF and forms a multicomplex with MITF and Hint. We have also shown that Ap4A, an endogenous molecule consisting of two adenosine linked by four phosphate which is known to be synthesized by LysRS, is accumulated intracellularily above 700 microM in IgE-Ag-activated mast cells, binds to Hint, liberates MITF, and thus leads to the activation of MITF-dependent gene expression. This implies that LysRS plays a key role via Ap4A as an important signaling molecule in MITF transcriptional activity.

Systematically convergent basis sets for transition metals. I. All-electron correlation consistent basis sets for the 3d elements Sc-Zn

NASA Astrophysics Data System (ADS)

Balabanov, Nikolai B.; Peterson, Kirk A.

2005-08-01

Sequences of basis sets that systematically converge towards the complete basis set (CBS) limit have been developed for the first-row transition metal elements Sc-Zn. Two families of basis sets, nonrelativistic and Douglas-Kroll-Hess (-DK) relativistic, are presented that range in quality from triple-ζ to quintuple-ζ. Separate sets are developed for the description of valence (3d4s) electron correlation (cc-pVnZ and cc-pVnZ-DK; n =T,Q, 5) and valence plus outer-core (3s3p3d4s) correlation (cc-pwCVnZ and cc-pwCVnZ-DK; n =T,Q, 5), as well as these sets augmented by additional diffuse functions for the description of negative ions and weak interactions (aug-cc-pVnZ and aug-cc-pVnZ-DK). Extensive benchmark calculations at the coupled cluster level of theory are presented for atomic excitation energies, ionization potentials, and electron affinities, as well as molecular calculations on selected hydrides (TiH, MnH, CuH) and other diatomics (TiF, Cu2). In addition to observing systematic convergence towards the CBS limits, both 3s3p electron correlation and scalar relativity are calculated to strongly impact many of the atomic and molecular properties investigated for these first-row transition metal species.

Discovery of 36 eclipsing EL CVn binaries found by the Palomar Transient Factory

NASA Astrophysics Data System (ADS)

van Roestel, J.; Kupfer, T.; Ruiz-Carmona, R.; Groot, P. J.; Prince, T. A.; Burdge, K.; Laher, R.; Shupe, D. L.; Bellm, E.

2018-04-01

We report on the discovery and analysis of 36 new eclipsing EL CVn-type binaries, consisting of a core helium-composition pre-white dwarf (pre-He-WD) and an early-type main-sequence companion. This more than doubles the known population of these systems. We have used supervised machine learning methods to search 0.8 million light curves from the Palomar Transient Factory (PTF), combined with Sloan Digital Sky Survey (SDSS), Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) and Two-Micron All-Sky Survey (2MASS) colours. The new systems range in orbital periods from 0.46 to 3.8 d and in apparent brightness from ˜14 to 16 mag in the PTF R or g΄ filters. For 12 of the systems, we obtained radial velocity curves with the Intermediate Dispersion Spectrograph at the Isaac Newton Telescope. We modelled the light curves, radial velocity curves and spectral energy distributions to determine the system parameters. The radii (0.3-0.7 R⊙) and effective temperatures (8000-17 000 K) of the pre-He-WDs are consistent with stellar evolution models, but the masses (0.12-0.28 M⊙) show more variance than models have predicted. This study shows that using machine learning techniques on large synoptic survey data is a powerful way to discover substantial samples of binary systems in short-lived evolutionary stages.

Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease.

PubMed

Lüscher, Christian; Huber, Kimberly M

2010-02-25

Many excitatory synapses express Group 1, or Gq coupled, metabotropic glutamate receptors (Gp1 mGluRs) at the periphery of their postsynaptic density. Activation of Gp1 mGluRs typically occurs in response to strong activity and triggers long-term plasticity of synaptic transmission in many brain regions, including the neocortex, hippocampus, midbrain, striatum, and cerebellum. Here we focus on mGluR-induced long-term synaptic depression (LTD) and review the literature that implicates Gp1 mGluRs in the plasticity of behavior, learning, and memory. Moreover, recent studies investigating the molecular mechanisms of mGluR-LTD have discovered links to mental retardation, autism, Alzheimer's disease, Parkinson's disease, and drug addiction. We discuss how mGluRs lead to plasticity of neural circuits and how the understanding of the molecular mechanisms of mGluR plasticity provides insight into brain disease.

Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.

PubMed

Cribb, Lachlan; Murphy, Jenifer; Froud, Amy; Oliver, Georgina; Bousman, Chad A; Ng, Chee H; Sarris, Jerome

2017-05-29

Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the pathophysiology of MDD.

Micro RNA-146a But Not IRAK1 is Associated with Rheumatoid Arthritis in the Tunisian Population.

PubMed

Hassine, Hana Ben; Boumiza, Asma; Sghiri, Rim; Baccouche, Khadija; Boussaid, Imen; Atig, Ahlem; Shakoor, Zahid; Bouajina, Elyes; Zemni, Ramzi

2017-02-01

Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR. Its gene expression is regulated by the micro-RNA (miR)-146a. We investigated the role of IRAK1 single-nucleotide polymorphism (SNP) rs3027898 (IRAK1 rs3027898) and miR-146a SNP rs2910164 (miR-146a rs2910164) in Tunisian patients with RA and their association with C reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibodies, and erosion. In a cohort of 172 adult RA patients and 224 matched controls, IRAK1 rs3027898 genotyping was determined by mutagenically separated polymerase chain reaction (MS-PCR) with newly designed primers, and miR-146a rs2910164 genotyping was determined by fragment length polymorphism PCR-restriction (RFLP-PCR). The IRAK1 rs3027898 A allele was detected in 67% of RA patients and 70% of controls indicating that it is not associated with RA in codominant, dominant, or recessive models even after stratification by age and gender. The miR-146a rs2910164 G allele was detected in 76% of RA patients and 68% of controls, thus the C allele confers some protection based on a dominant model [CC+GC (odds ratio (95% confidence interval) = 0.6 (0.3-0.9), p = 0.03)]. No association with CRP, RF, anti-CCP, or erosion was found for either SNPs. The IRAK1 rs3027898 was not associated with RA, whereas C allele of miR-146a rs2910164 was found to be protective. Functional studies are required to investigate the exact role of miR-146a rs2910164 during RA.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

PubMed

López-Rodríguez, Rosario; Hernández-Bartolomé, Ángel; Borque, María Jesús; Rodríguez-Muñoz, Yolanda; Martín-Vílchez, Samuel; García-Buey, Luisa; González-Moreno, Leticia; Real-Martínez, Yolanda; Muñoz de Rueda, Paloma; Salmerón, Javier; Vidal-Castiñeira, José Ramón; López-Larrea, Carlos; Rodrigo, Luis; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

2017-01-01

Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome.

PubMed

Fabio, Rosa Angela; Billeci, Lucia; Crifaci, Giulia; Troise, Emilia; Tortorella, Gaetano; Pioggia, Giovanni

2016-01-01

Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters. The aim of this study was to investigate whether behaviors and brain activity were modified by training in RS. The modifications were assessed in two phases: (a) after a short-term training (STT) session, i.e., after 30 min of training and (b) after long-term training (LTT), i.e., after 5 days of training. Thirty-four girls with RS were divided into two groups: a training group (21 girls) who underwent the LTT and a control group (13 girls) that did not undergo LTT. The gaze and quantitative EEG (QEEG) data were recorded during the administration of the tasks. A gold-standard eye-tracker and a wearable EEG equipment were used. Results suggest that the participants in the STT task showed a habituation effect, decreased beta activity and increased right asymmetry. The participants in the LTT task looked faster and longer at the target, and show increased beta activity and decreased theta activity, while a leftward asymmetry was re-established. The overall result of this study indicates a positive effect of long-term cognitive training on brain and behavioral parameters in subject with RS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic variants in the vitamin D pathway and breast cancer disease-free survival

PubMed Central

Brewster, Abenaa M.

2013-01-01

Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients. PMID:23180655

Single-Nucleotide Polymorphisms of FAS and FASL Genes and Risk of Idiopathic Aplastic Anemia.

PubMed

Rehman, Sadia; Saba, Nusrat; Naz, Madiha; Ahmed, Parvez; Munir, Saeeda; Sajjad, Sumaira; Tabassum, Sobia; Naseem, Lubna

2018-04-03

FAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities. Several single-nucleotide polymorphisms (SNPs) of FAS/FASL system can result in aberrant apoptosis, which can cause different cancers and autoimmune diseases. Aplastic anemia (AA) is an autoimmune dysfunction characterized by peripheral blood pancytopenia associated with hypoplasia of bone marrow. The aim of this study was to screen Pakistani AA patients and controls for two Fas SNPs rs2234767 and rs1800682 and two FASLG SNPs rs763110 and rs5030772. Genotyping of 392 DNA samples was done by Tetra-ARMS polymerase chain reaction. Genotypic frequencies of Fas rs1800682 and FASLG rs5030772 showed significance difference in their distribution in both controls and patients, while Fas rs2234767 and FASLG rs763110 SNPs had no such difference. Carriers of rs1800682 AG+GG had a very odd ratio of 4.63, with 95% confidence interval (CI) of 3.01-7.11, while individuals with FASLG rs5030772 AG+GG were more common in controls than patients with OR 0.53 and 95% CI of 0.34-0.83. Cumulative effects of these SNPs were analyzed, and they showed almost similar trends; however, Fas rs2234767 and FASLG rs763110 genotypes in combination with Fas rs1800682 and FASLG rs5030772 demonstrated significant association. This study provided information that endorsed the involvement of FAS/FASL system SNPs in the pathogenesis of AA; further studies should be designed to understand the exact role of SNPs that can help in early diagnosis and treatment.

Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome.

PubMed

Latuskiewicz-Potemska, Joanna; Chmura-Skirlinska, Antonina; Gurbiel, Ryszard J; Smolewska, Elzbieta

2016-08-01

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

PubMed

Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

2016-01-01

Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines.

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

PubMed

Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

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. © 2014 Blackwell Verlag GmbH.

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels

PubMed Central

Zhu, Yi-bing; Huang, Rong-dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = —0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

Embodying a cognitive model in a mobile robot

NASA Astrophysics Data System (ADS)

Benjamin, D. Paul; Lyons, Damian; Lonsdale, Deryle

2006-10-01

The ADAPT project is a collaboration of researchers in robotics, linguistics and artificial intelligence at three universities to create a cognitive architecture specifically designed to be embodied in a mobile robot. There are major respects in which existing cognitive architectures are inadequate for robot cognition. In particular, they lack support for true concurrency and for active perception. ADAPT addresses these deficiencies by modeling the world as a network of concurrent schemas, and modeling perception as problem solving. Schemas are represented using the RS (Robot Schemas) language, and are activated by spreading activation. RS provides a powerful language for distributed control of concurrent processes. Also, The formal semantics of RS provides the basis for the semantics of ADAPT's use of natural language. We have implemented the RS language in Soar, a mature cognitive architecture originally developed at CMU and used at a number of universities and companies. Soar's subgoaling and learning capabilities enable ADAPT to manage the complexity of its environment and to learn new schemas from experience. We describe the issues faced in developing an embodied cognitive architecture, and our implementation choices.

The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood.

PubMed

Nam, Dae Cheol; Ha, Yu Mi; Park, Min Kyu; Cho, Sung Kweon

2016-08-01

Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.

APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases.

PubMed

Zhang, Rui-Nan; Zheng, Rui-Dan; Mi, Yu-Qiang; Zhou, Da; Shen, Feng; Chen, Guang-Yu; Zhu, Chan-Yan; Pan, Qin; Fan, Jian-Gao

2016-08-01

The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese. Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped. Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p < 0.01) between groups of NAFLD and control. After adjusting for sex, age, serum triglycerides, total cholesterol, body mass index, and the PNPLA3 rs738409 polymorphism, the APOC3 rs2070666 A allele was an independent risk factor for NAFLD with an odds ratio (OR) of 3.683 and 95 % confidence interval (CI) of 1.037-13.084. The APOC3 rs2070666 A allele was linked to the fourth quartile of the controlled attenuation parameter values (OR 2.769, 95 % CI 1.002-7.651) in 131 subjects, and also linked to the significant histological steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients. The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

Requirement of extracellular Ca2+ binding to specific amino acids for heat‐evoked activation of TRPA1

PubMed Central

Kurganov, Erkin; Saito, Shigeru; Tanaka Saito, Claire

2017-01-01

Key points We found that extracellular Ca2+, but not other divalent cations (Mg2+ and Ba2+) or intracellular Ca2+, is involved in heat‐evoked activation of green anole (ga) TRPA1.Heat‐evoked activation of chicken (ch) and rat snake (rs) TRPA1 does not depend solely on extracellular Ca2+.Neutralization of acidic amino acids on the outer surface of TRPA1 by extracellular Ca2+ is important for heat‐evoked large activation of gaTRPA1, chTRPA1 and rsTRPA1. Abstract Transient receptor potential ankyrin 1 (TRPA1) is a homotetrameric non‐selective cation‐permeable channel that has six transmembrane domains and cytoplasmic N‐ and C‐termini. The N‐terminus is characterized by an unusually large number of ankyrin repeats. Although the 3‐dimensional structure of human TRPA1 has been determined, and TRPA1 channels from insects to birds are known to be activated by heat stimulus, the mechanism for temperature‐dependent TRPA1 activation is unclear. We previously reported that extracellular Ca2+, but not intracellular Ca2+, plays an important role in heat‐evoked TRPA1 activation in green anole lizards (gaTRPA1). Here we focus on extracellular Ca2+‐dependent heat sensitivity of gaTRPA1 by comparing gaTRPA1 with heat‐activated TRPA1 channels from rat snake (rsTRPA1) and chicken (chTRPA1). In the absence of extracellular Ca2+, rsTRPA1 and chTRPA1 are activated by heat and generate small inward currents. A comparison of extracellular amino acids in TRPA1 identified three negatively charged amino acid residues (glutamate and aspartate) near the outer pore vestibule that are involved in heat‐evoked TRPA1 activation in the presence of extracellular Ca2+. These results suggest that neutralization of acidic amino acids by extracellular Ca2+ is important for heat‐evoked activation of gaTRPA1, chTRPA1, and rsTRPA1, which could clarify mechanisms of heat‐evoked channel activation. PMID:28194754

TRPV1 Gene Polymorphisms Are Associated with Type 2 Diabetes by Their Interaction with Fat Consumption in the Korean Genome Epidemiology Study.

PubMed

Park, Sunmin; Zhang, Xin; Lee, Na Ra; Jin, Hyun-Seok

2016-01-01

Different transient receptor potential vanilloid 1 (TRPV1) variants may be differently activated by noxious stimuli. We investigated how TRPV1 variants modulated the prevalence of type 2 diabetes and specific gene-nutrient interactions. Among 8,842 adults aged 40-69 years in the Korean Genome Epidemiology Study, the associations between TRPV1 genotypes and the prevalence of type 2 diabetes as well as their gene-nutrient interactions were investigated after adjusting for the covariates of age, gender, residence area, body mass index, daily energy intake, and total activity. The TRPV1 rs161364 and rs8065080 minor alleles lowered HOMA-IR and the risk of type 2 diabetes after adjusting for covariates. There were gene-nutrient interactions between TRPV1 variants rs161364 and rs8065080 and preference for oily taste, intake of oily foods, and fat intake after adjusting for covariates. Among subjects with the minor alleles of TRPV1 rs161364 and rs8065080, the group with a high preference for oily foods had a lower odds ratio for type 2 diabetes. Consistent with the preference for taste, among subjects with the minor alleles, the group with high fat intake from oily foods also exhibited a lower risk of type 2 diabetes than subjects with the major alleles. People with the minor alleles of the TRPV1 single nucleotide polymorphisms rs161364 and rs8065080 have a lower risk of diabetes with a high-fat diet, but people with the major alleles are at a higher risk of type 2 diabetes when consuming high-fat diets. The majority of people should be careful about a high fat intake. © 2016 S. Karger AG, Basel.

Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

PubMed Central

Chadha, Sanya; Mallampudi, N. Arjunreddy; Mohapatra, Debendra K.

2017-01-01

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target. PMID:28875178

Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity.

PubMed

Chadha, Sanya; Mallampudi, N Arjunreddy; Mohapatra, Debendra K; Madhubala, Rentala

2017-01-01

Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase ( Ld LysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. Ld LysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas Ld LysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized Ld LysRS-1. Recombinant Ld LysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The Ld LysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. Ld LysRS-1 appears to be an essential gene, as a chromosomal knockout of Ld LysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC 50 ], 4.19 µM) and intracellular amastigotes (IC 50 , 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using Ld LysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant Ld LysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases ( Ld LysRS) are present in this parasite. Ld LysRS-1 is closer to apicomplexans and eukaryotes, whereas Ld LysRS-2 is closer to bacteria. Here, we have characterized Ld LysRS-1 of L. donovani . Ld LysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore Ld LysRS-1 as a potential drug target.

Improved iodine radiolabels for monoclonal antibody therapy.

PubMed

Stein, Rhona; Govindan, Serengulam V; Mattes, M Jules; Chen, Susan; Reed, Linda; Newsome, Guy; McBride, Bill J; Griffiths, Gary L; Hansen, Hans J; Goldenberg, David M

2003-01-01

A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs. We recently reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a residualizing iodine label that overcame many of the limitations that had impeded the development of residualizing iodine for clinical use. To determine the factors governing the therapeutic index of the labeled MAb, as well as the factors required for production of radioiodinated MAb in high yield and with high specific activity, variations in the peptide structure of IMP-R1 were evaluated. A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and charge were compared. Radioiodinations of the peptides followed by conjugations to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished radioimmunoconjugates in good overall incorporations, with immunoreactivities comparable to that of directly radioiodinated RS7. Specific activities of up to 8 mCi/mg and yields > 80% have been achieved. In vitro processing experiments showed marked increases in radioiodine retention with all of the adducts; radioiodine retention at 45 h was up to 86% greater in cells than with directly iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I-RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies in nude mice bearing human lung tumor xenografts. All of the residualizing substrates exhibited significantly enhanced retention in tumor in comparison to directly radioiodinated RS7, but the nontarget uptakes differed significantly among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention and low normal organ uptake, as well as superior radiochemical properties. The therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7 were equivalent, and both agents yielded significantly improved control of tumor growth compared with conventional (131)I-labeled RS7.

Interactions between social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China.

PubMed

Zeng, Yi; Cheng, Lingguo; Zhao, Ling; Tan, Qihua; Feng, Qiushi; Chen, Huashuai; Shen, Ke; Li, Jianxin; Zhang, Fengyu; Cao, Huiqing; Gregory, Simon G; Yang, Ze; Gu, Jun; Tao, Wei; Tian, Xiao-Li; Hauser, Elizabeth R

2013-09-09

Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap. We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers. The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

PubMed

Matsuzaka, Camila T; Christofolini, Denise; Ota, Vanessa K; Gadelha, Ary; Berberian, Arthur A; Noto, Cristiano; Mazzotti, Diego R; Spindola, Leticia M; Moretti, Patricia N; Smith, Marilia A C; Melaragno, Maria I; Belangero, Sintia I; Bressan, Rodrigo A

2017-01-01

Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Association of BDNF Polymorphisms with the Risk of Epilepsy: a Multicenter Study.

PubMed

Sha'ari, Hidayati Mohd; Haerian, Batoul Sadat; Baum, Larry; Tan, Hui Jan; Rafia, Mohd Hanip; Kwan, Patrick; Cherny, Stacey S; Sham, Pak Chung; Gui, Hongsheng; Raymond, Azman Ali; Lim, Kheng Seang; Mohamed, Zahurin

2016-07-01

Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.

Effects of circadian clock genes and environmental factors on cognitive aging in old adults in a Taiwanese population.

PubMed

Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C; Kao, Chung-Feng; Tsai, Shih-Jen

2017-04-11

Previous animal studies have indicated associations between circadian clock genes and cognitive impairment . In this study, we assessed whether 11 circadian clockgenes are associated with cognitive aging independently and/or through complex interactions in an old Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to evaluate cognitive function. Our data showed associations between cognitive aging and single nucleotide polymorphisms (SNPs) in 4 key circadian clock genes, CLOCK rs3749473 (p = 0.0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and RORB rs10781247 (p = 7.9 x 10-5). We also found that interactions between CLOCK rs3749473, NPAS2 rs17655330, RORA rs13329238, and RORB rs10781247 affected cognitive aging (p = 0.007). Finally, we investigated the influence of interactions between CLOCK rs3749473, RORA rs13329238, and RORB rs10781247 with environmental factors such as alcohol consumption, smoking status, physical activity, and social support on cognitive aging (p = 0.002 ~ 0.01). Our study indicates that circadian clock genes such as the CLOCK, NPAS2, RORA, and RORB genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-environment interactions.

Macrophage Migration Inhibitory Factor (MIF) Gene Promotor Polymorphism Is Associated with Increased Fibrosis in Biliary Atresia Patients, but Not with Disease Susceptibility.

PubMed

Sadek, Khaled H; Ezzat, Sameera; Abdel-Aziz, Samira A; Alaraby, Hanaa; Mosbeh, Asmaa; Abdel-Rahman, Mohamed H

2017-09-01

Two polymorphisms, rs755622 and rs5844572, in the promoter region of the macrophage migration inhibitory factor (MIF) gene influence the basal and/or induced transcriptional activity and have been linked to several inflammatory and autoimmune diseases. The aim of this study was to investigate the association between these two polymorphisms and disease susceptibility in patients with biliary atresia (BA). Allele frequencies of rs755622 and rs5844572 were assessed in 60 Egyptian infants with a confirmed diagnosis of BA. DNA was extracted from archival material. For the rs755622, samples were tested using Taqman real-time PCR, and for the rs5844572, samples were tested using fluorescence-based genotyping. The allele frequency in the general population was assessed in 141 healthy adults from the same geographical location. No statistical differences were observed in the allele frequencies of either rs755622 or rs5844572 between BA patients and controls. The homozygous and heterozygous short repeats (5/5, or 5/X) of rs5844572 were observed more frequently (16/28, 57.1%) in BA patients with mild to moderate fibrosis compared with those with marked fibrosis (10/32, 31.3%). The difference was statistically significant (P  =  0.032). In conclusion, we observed no association between MIF rs755622 and rs5844572 polymorphisms and susceptibility to BA; however, the rs5844572 could be linked to the rate of progression of the disease and extent of fibrosis. © 2017 John Wiley & Sons Ltd/University College London.

Five endometrial cancer risk loci identified through genome-wide association analysis.

PubMed

Cheng, Timothy Ht; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica Mj; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Consortium, Chibcha; Jun Li, Mulin; Yip, Shun H; Wang, Junwen; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Dunlop, Malcolm; Houlston, Richard; Palles, Claire; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Cunningham, Julie M; Pharoah, Paul D P; Dunning, Alison M; Edwards, Stacey L; Easton, Douglas F; Tomlinson, Ian; Spurdle, Amanda B

2016-06-01

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

PubMed Central

Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C. H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

2017-01-01

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. PMID:28165464

Remote sensing science for the Nineties; Proceedings of IGARSS '90 - 10th Annual International Geoscience and Remote Sensing Symposium, University of Maryland, College Park, May 20-24, 1990. Vols. 1, 2, & 3

NASA Technical Reports Server (NTRS)

1990-01-01

Various papers on remote sensing (RS) for the nineties are presented. The general topics addressed include: subsurface methods, radar scattering, oceanography, microwave models, atmospheric correction, passive microwave systems, RS in tropical forests, moderate resolution land analysis, SAR geometry and SNR improvement, image analysis, inversion and signal processing for geoscience, surface scattering, rain measurements, sensor calibration, wind measurements, terrestrial ecology, agriculture, geometric registration, subsurface sediment geology, radar modulation mechanisms, radar ocean scattering, SAR calibration, airborne radar systems, water vapor retrieval, forest ecosystem dynamics, land analysis, multisensor data fusion. Also considered are: geologic RS, RS sensor optical measurements, RS of snow, temperature retrieval, vegetation structure, global change, artificial intelligence, SAR processing techniques, geologic RS field experiment, stochastic modeling, topography and Digital Elevation model, SAR ocean waves, spaceborne lidar and optical, sea ice field measurements, millimeter waves, advanced spectroscopy, spatial analysis and data compression, SAR polarimetry techniques. Also discussed are: plant canopy modeling, optical RS techniques, optical and IR oceanography, soil moisture, sea ice back scattering, lightning cloud measurements, spatial textural analysis, SAR systems and techniques, active microwave sensing, lidar and optical, radar scatterometry, RS of estuaries, vegetation modeling, RS systems, EOS/SAR Alaska, applications for developing countries, SAR speckle and texture.

Metabotropic glutamate receptors in auditory processing

PubMed Central

Lu, Yong

2014-01-01

As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for treatment of brain disorders. Here, I review the studies on mGluRs in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus has been well characterized, while data for other auditory nuclei await more systematic investigations at both the light and electron microscopy levels. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the lower auditory brainstem in both mammals and birds. These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted. PMID:24909898

Functional Analysis of a Novel Genome-Wide Association Study Signal in SMAD3 That Confers Protection From Coronary Artery Disease.

PubMed

Turner, Adam W; Martinuk, Amy; Silva, Anada; Lau, Paulina; Nikpay, Majid; Eriksson, Per; Folkersen, Lasse; Perisic, Ljubica; Hedin, Ulf; Soubeyrand, Sebastien; McPherson, Ruth

2016-05-01

A recent genome-wide association study meta-analysis identified an intronic single nucleotide polymorphism in SMAD3, rs56062135C>T, the minor allele (T) which associates with protection from coronary artery disease. Relevant to atherosclerosis, SMAD3 is a key contributor to transforming growth factor-β pathway signaling. Here, we seek to identify ≥1 causal coronary artery disease-associated single nucleotide polymorphisms at the SMAD3 locus and characterize mechanisms whereby the risk allele(s) contribute to coronary artery disease risk. By genetic and epigenetic fine mapping, we identified a candidate causal single nucleotide polymorphism rs17293632C>T (D', 0.97; r(2), 0.94 with rs56062135) in intron 1 of SMAD3 with predicted functional effects. We show that the sequence encompassing rs17293632 acts as a strong enhancer in human arterial smooth muscle cells. The common allele (C) preserves an activator protein (AP)-1 site and enhancer function, whereas the protective (T) allele disrupts the AP-1 site and significantly reduces enhancer activity (P<0.001). Pharmacological inhibition of AP-1 activity upstream demonstrates that this allele-specific enhancer effect is AP-1 dependent (P<0.001). Chromatin immunoprecipitation experiments reveal binding of several AP-1 component proteins with preferential binding to the (C) allele. We show that rs17293632 is an expression quantitative trait locus for SMAD3 in blood and atherosclerotic plaque with reduced expression of SMAD3 in carriers of the protective allele. Finally, siRNA knockdown of SMAD3 in human arterial smooth muscle cells increases cell viability, consistent with an antiproliferative role. The coronary artery disease-associated rs17293632C>T single nucleotide polymorphism represents a novel functional cis-acting element at the SMAD3 locus. The protective (T) allele of rs17293632 disrupts a consensus AP-1 binding site in a SMAD3 intron 1 enhancer, reduces enhancer activity and SMAD3 expression, altering human arterial smooth muscle cell proliferation. © 2016 American Heart Association, Inc.

Enhancement of Protective Effects of Radix Scutellariae on UVB-induced Photo Damage in Human HaCaT Keratinocytes.

PubMed

Wang, Yu-Shuai; Cho, Jin-Gyeong; Hwang, Eun-Son; Yang, Jung-Eun; Gao, Wei; Fang, Min-Zhe; Zheng, Sheng-Dao; Yi, Tae-Hoo

2018-04-01

Radix Scutellariae (RS) has long been used in the treatment of inflammatory and allergic diseases. Its main flavonoids, baicalin (BG) and wogonoside (WG), can be hydrolyzed into their corresponding aglycones, baicalein (B) and wogonin (W). In this study, we developed a safe and effective method of transforming these glycosides using Peclyve PR. The transformation rate of BG and WG reached 98.5 and 98.1%, respectively, with 10% enzyme at 40 °C for 60 h. Furthermore, we compared the anti-photoaging activity of RS before and after enzyme treatment, as well as their respective main components, in UVB-irradiated HaCaT cells. Results found that enzyme-treated RS (ERS) appeared to be much better at preventing UVB-induced photoaging than RS. ERS significantly inhibited the upregulation of matrix metalloproteinase-1 and IL-6 caused by UVB radiation by inactivating the MAPK/AP-1 and NF-κB/IκB-α signaling pathways. ERS treatment also recovered UVB-induced reduction of procollagen type I by activating the TGF-β/Smad pathway. In addition, ERS exhibited an excellent antioxidant activity, which could increase the expression of cytoprotective antioxidants such as HO-1 and NQ-O1, by facilitating Nrf2 nuclear transfer. These findings demonstrated that the photoprotective effects of RS were significantly improved by enzyme-modified biotransformation.

Local Control Models of Cardiac Excitation–Contraction Coupling

PubMed Central

Stern, Michael D.; Song, Long-Sheng; Cheng, Heping; Sham, James S.K.; Yang, Huang Tian; Boheler, Kenneth R.; Ríos, Eduardo

1999-01-01

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation–contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation–contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution. PMID:10051521

Coincident postsynaptic activity gates presynaptic dopamine release to induce plasticity in Drosophila mushroom bodies

PubMed Central

Ueno, Kohei; Suzuki, Ema; Naganos, Shintaro; Ofusa, Kyoko; Horiuchi, Junjiro; Saitoe, Minoru

2017-01-01

Simultaneous stimulation of the antennal lobes (ALs) and the ascending fibers of the ventral nerve cord (AFV), two sensory inputs to the mushroom bodies (MBs), induces long-term enhancement (LTE) of subsequent AL-evoked MB responses. LTE induction requires activation of at least three signaling pathways to the MBs, mediated by nicotinic acetylcholine receptors (nAChRs), NMDA receptors (NRs), and D1 dopamine receptors (D1Rs). Here, we demonstrate that inputs from the AL are transmitted to the MBs through nAChRs, and inputs from the AFV are transmitted by NRs. Dopamine signaling occurs downstream of both nAChR and NR activation, and requires simultaneous stimulation of both pathways. Dopamine release requires the activity of the rutabaga adenylyl cyclase in postsynaptic MB neurons, and release is restricted to MB neurons that receive coincident stimulation. Our results indicate that postsynaptic activity can gate presynaptic dopamine release to regulate plasticity. DOI: http://dx.doi.org/10.7554/eLife.21076.001 PMID:28117664

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons

PubMed Central

Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi

2017-01-01

Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549

Orbitofrontal Cortical Neurons Encode Expectation-Driven Initiation of Reward-Seeking

PubMed Central

Aston-Jones, Gary

2014-01-01

Adaptive execution and inhibition of behavior are guided by the activity of neuronal populations across multiple frontal cortical areas. The rodent medial prefrontal cortex has been well studied with respect to these behaviors, influencing behavioral execution/inhibition based on context. Other frontal regions, in particular the orbitofrontal cortex (OFC), are critical in directing behavior to obtain rewards, but the relationship between OFC neuronal activity and response execution or inhibition has been poorly characterized. In particular, little is known about OFC with respect to extinction learning, an important example of context-guided response inhibition. Here, we recorded the activity of OFC neurons while rats performed a discriminative-stimulus (DS)-driven sucrose-seeking task followed by multiple days of extinction of the DS. OFC neuronal activity was maximally responsive (1) to reward-predicting stimuli (RS) that triggered a lever press (i.e., lever-response initiation) and (2) during reward-well approach in pursuit of sucrose (i.e., well-response initiation). RS presentation that was not followed by a lever press or RS presentation during extinction produced weak activation, as did nonrewarded stimulus (NS) presentation regardless of response (press or withhold) or session (DS-sucrose or extinction). Activity related to nonrewarded well entry was minor, and activity was significantly inhibited during reward consumption. Finally, OFC neuronal activity switched selectivity to track rewarded behaviors when the RS/NS contingencies were reversed. Thus, rather than signaling variables related to extinction or response inhibition, activity in OFC was strongest at the initiation of multiple components of reward-seeking behavior, most prominently when valid reward-predicting cues drove these behaviors. PMID:25080585

Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons.

PubMed

Nakahata, Yoshihisa; Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Kuriu, Toshihiko; Hirata, Hiromi; Moorhouse, Andrew J; Ishibashi, Hitoshi; Nabekura, Junichi

2017-01-01

Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo . While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca 2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system.

Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

PubMed

Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

2013-11-01

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE. Copyright © 2013 by the American College of Rheumatology.

Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans.

PubMed

Laffer, Cheryl L; Elijovich, Fernando; Eckert, George J; Tu, Wanzhu; Pratt, J Howard; Brown, Nancy J

2014-07-01

An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742 (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3 ± 7.3/-3.2 ± 4.0 vs. +6.8 ± 7.9/+4.8 ± 8.6 mm Hg, P < .01/<.05). The aldosterone response to spironolactone was also blunted in the CC genotype. In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Beyond genome-wide scan: Association of a cis-regulatory NCR3 variant with mild malaria in a population living in the Republic of Congo.

PubMed

Baaklini, Sabrina; Afridi, Sarwat; Nguyen, Thy Ngoc; Koukouikila-Koussounda, Felix; Ndounga, Mathieu; Imbert, Jean; Torres, Magali; Pradel, Lydie; Ntoumi, Francine; Rihet, Pascal

2017-01-01

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.

Platelet monoamine oxidase type B, MAOB intron 13 and MAOA-uVNTR polymorphism and symptoms of post-traumatic stress disorder.

PubMed

Svob Strac, Dubravka; Kovacic Petrovic, Zrnka; Nikolac Perkovic, Matea; Umolac, Danica; Nedic Erjavec, Gordana; Pivac, Nela

2016-07-01

Post-traumatic stress disorder (PTSD), a disorder that develops following exposure to traumatic experience(s), is frequently associated with agitation, aggressive behavior and psychotic symptoms. Monoamine oxidase (MAO) degrades different biogenic amines and regulates mood, emotions and behavior, and has a role in the pathophysiology of various neuropsychiatric disorders. The aim of the study was to investigate the association between different symptoms occurring in PTSD [PTSD symptom severity assessed by the Clinician Administered PTSD Scale (CAPS), agitation and selected psychotic symptoms assessed by the Positive and Negative Syndrome Scale (PANSS)] and platelet MAO-B activity and/or genetic variants of MAOB rs1799836 and MAOA-uVNTR polymorphisms in 249 Croatian male veterans with PTSD. Our study revealed slightly higher platelet MAO-B activity in veterans with PTSD with more severe PTSD symptoms and in veterans with agitation, and significantly higher platelet MAO-B activity in veterans with more pronounced psychotic symptoms compared to veterans with less pronounced psychotic symptoms. Platelet MAO-B activity was associated with smoking but not with age. Genetic variants of MAOB rs1799836 and MAOA-uVNTR were not associated with agitation and selected psychotic symptoms in veterans with PTSD. A marginally significant association was found between MAOB rs1799836 polymorphism and severity of PTSD symptoms, but it was not confirmed since carriers of G or A allele of MAOB rs1799836 did not differ in their total CAPS scores. These findings suggest an association of platelet MAO-B activity, but a lack of association of MAOB rs1799836 and MAOA-uVNTR, with selected psychotic symptoms in ethnically homogenous veterans with PTSD.

Hα spectroscopy and BV photometry of RT Lacertae

NASA Astrophysics Data System (ADS)

Frasca, A.; Çakırlı, Ö.; Catalano, S.; Ibanoǧlu, C.; Marilli, E.; Evren, S.; Taş, G.

2002-06-01

Contemporaneous spectroscopic and photometric B V observations of the RS CVn type eclipsing binary RT Lacertae were performed in summer 2000. The photometric observations were obtained at the Ege University Observatory, while the spectroscopic ones were carried out at Catania Astrophysical Observatory in the spectral range 5860-6700 Å. We obtained a high quality radial velocity curve of the system that allowed us to give more accurate values of the orbital parameters. A steady decrease of the barycentric velocity from 1920 to 2000 has been pointed out and has been discussed in the context of a third body hypothesis. Through the subtraction of a ``synthetic'' spectrum, built up with spectra of inactive standard stars, we detected Hα excess emission which fills in the photospheric absorption profiles of both components. With the exception of a few spectra, taken close to the eclipses, in which some extra absorption or a faint double-peaked broad emission appears, there is no further evidence of circumstellar matter in this system, as suggested in previous works. The hotter and more massive star appears also as the more active at a chromospheric level, since it has a Hα flux about ten times greater than the companion, on average. Rotational modulation of the Hα emission has been detected in both stars. The hemisphere of the more massive star facing the observer at phase 0fp75 appears brighter (in Hα ) than that seen at phase 0fp25 , while for the less massive G9 IV star the maximum Hα emission is seen around phase 0fp0-0fp1 . From the analysis of the contemporaneous light curve (Lanza et al. \\cite{Lanza2001}), the more massive G5 IV star results to be more active than the companion at a photospheric level, in agreement with the chromospheric behaviour observed in Hα . In addition, the starspots of the G5 IV star are mainly located in the Hα brighter hemisphere, suggesting a close spatial association of spots and plages in this star. The G9 IV star displays instead the maximum Hα emission at the phase of maximum visibility of the smaller spotted area found from the light-curve analysis. The minimum Hα emission occurs when the more heavily spotted region is visible. Based on observations collected at Catania Astrophysical Observatory, Italy, and at Ege University Observatory, Turkey. Table 1 only available 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/388/298

A Limited Flight Test Investigation of Pilot-Induced Oscillation Due to Elevator Rate Limiting (HAVE LIMITS)

DTIC Science & Technology

1997-06-01

c10ioid@ #-w odor n .Oprsiw ri rpw,20503.nDvi ,tws ot 1. AG__USE u NLY (~tLeswblit) 2. RCEPORNTODATE 3 REPORToTYYE A55W? O~flCCCOV9ISRO June 1997 Final...discussed. The test analyses of the results. iii r - This page irwk’idonally left blnk. - 3 DI ivI ®I S EXE.CVnWV% This rmport prsets the results of a...I........................... 3 Verification of Ahtra• Modai

Fatigue and Fracture-Toughness Characterization of SAW and SMA A537 Class I Ship-Steel Weldments.

DTIC Science & Technology

1981-12-01

Charpy criterion and proposed NDT-DT criterion of Rolfe . Recommendations are made and further research is suggested to help clarify the assessment of...acceptable performance at -60aF. Likewise, at -60OF the NDT and DT data for these weldments marginally exceed the criteria proposed by Rolfe when the...exceed the CVN values equivalent to the 5/8 DT values required by Rolfe . The 5/8-inch dynamic-tear specimen is not recommended as a quality-control test

Spectroscopic study of the star Canum Venat (G0)

NASA Astrophysics Data System (ADS)

Mentese, H. H.

In this work the effective temperature and surface gravity of the star BetaCVn were determined by means of the theoretical profiles calculated by De Jager and Neven (1967-1968). The best agreement was obtained for T(eff) = 5940 K and log g = 4. The values of the excitation temperatures for Ti, Cr, Mn, and Fe were calculated and found to be very close to each other. The abundances of the elements were obtained by the growth curve method and found to be normal.

Joint Precision Approach and Landing System Nunn-McCurdy Breach Root Cause Analysis and Portfolio Assessment Metrics for DoD Weapons Systems. Volume 8

DTIC Science & Technology

2015-01-01

system that would help in adverse weather conditions. U.S. operations in Bosnia, which were run from a relatively austere airfield with limited air... operations beginning in 2013 (CVN21, Joint Strike Fighter, Joint Unmanned Combat Air System ). cAccording to multiple FAA ofcial planning documents...Positioning System Next Generation Operational Control System HMS Handheld, Manpack and Small Form Fit HUD Head up Display IAMD Integrated Air and

Swift observations of SDSS J141118.31+481257.6 during its first detected outburst

NASA Astrophysics Data System (ADS)

Sandoval, L. E. Rivera; Maccarone, T.

2018-05-01

We report Swift observations of the AM CVn-type system SDSS J141118.31+481257.6 (RA=14:11:18.31, Dec=+48:12:57.6) during its first ever recorded outburst. The system was detected by Tadashi Kojima on 2018-May-20 with a V magnitude of 12.6 +- 0.2 (http://ooruri.kusastro.kyoto-u.ac.jp/mailarchive/vsnet-alert/22176), an increase of 7 mags compared to any previous measurement in the same filter.

Marine Structural Steel Toughness Data Bank. Volume 3

DTIC Science & Technology

1991-08-28

Headings: Break? Did specimen fracture completely? CODIc Critical COD CODi Initial COD CVN Energy Charpy V Energy Crack lgth Crack Length Curve Curve...BS5762 -Standard Year Test Temp CODIc degC mm -30 0.57 -30 0.68 -30 . 1.26 not rporw(continued) Main Stutua To n ssDta:an Material BS4360 Gr50D Page...Initial JI. . . .. ._I. . . Maximum 1, ]max * Tearing Modulus ......... Standard Method ~P S5762 -Standard Year_______________ Test Tcmp CODIc degC mm

Effect of Thermal Treatment on the Mechanical and Toughness Properties of Extruded Sic sub w/Aluminum 6061 Metal Matrix Composite.

DTIC Science & Technology

1987-01-31

Charpy V-Notch_,,... i9,, STRACT (Continue on reverse if necessary and identify by block number) Mechanical, instrumented\\ Charpy V-potch (CVN) energy and...authors express their appreciation to Messrs. W. Willard and R. Gray for the fracture testing, Ensign M. Rennie for the instrumented Charpy V-notch...TO ALUMINUM GRAIN BOUNDARIES . . . . . . . . . 12 5 INSTRUMENTED CHARPY V-NOTCH LOAD AND ENERGY AGAINST TIME OUTPUTS FOR L-C ORIENTATION SiCwJAI 6061

Applying Risk Management to Reduce The Overall Time In Lay-Up While Increasing the Cost Effectiveness of a Nimitz (CVN 68) Class Aircraft Carrier in Dry Dock During the Execution Phase of a Refueling and Complex Overhaul

DTIC Science & Technology

2009-03-01

operational availability and modernization capability. 15. NUMBER OF PAGES 137 14. SUBJECT TERMS Systems Engineering Process, Risk Management...MASTER OF SCIENCE IN SYSTEMS ENGINEERING from the NAVAL POSTGRADUATE SCHOOL March 2009 Author: Kiah Bernard Rahming Approved by...Professor Gary O. Langford Thesis Advisor Dr. Paul V. Shebalin Second Reader Dr. David H. Olwell Chairman, Department of Systems