Binarity and Variable Stars in the Open Cluster NGC 2126

NASA Astrophysics Data System (ADS)

Chehlaeh, Nareemas; Mkrtichian, David; Kim, Seung-Lee; Lampens, Patricia; Komonjinda, Siramas; Kusakin, Anatoly; Glazunova, Ljudmila

2018-04-01

We present the results of an analysis of photometric time-series observations for NGC 2126 acquired at the Thai National Observatory (TNO) in Thailand and the Mount Lemmon Optical Astronomy Observatory (LOAO) in USA during the years 2004, 2013 and 2015. The main purpose is to search for new variable stars and to study the light curves of binary systems as well as the oscillation spectra of pulsating stars. NGC 2126 is an intermediate-age open cluster which has a population of stars inside the δ Scuti instability strip. Several variable stars are reported including three eclipsing binary stars, one of which is an eclipsing binary star with a pulsating component (V551 Aur). The Wilson-Devinney technique was used to analyze its light curves and to determine a new set of the system’s parameters. A frequency analysis of the eclipse-subtracted light curve was also performed. Eclipsing binaries which are members of open clusters are capable of delivering strong constraints on the cluster’s properties which are in turn useful for a pulsational analysis of their pulsating components. Therefore, high-resolution, high-quality spectra will be needed to derive accurate component radial velocities of the faint eclipsing binaries which are located in the field of NGC 2126. The new Devasthal Optical Telescope, suitably equipped, could in principle do this.

Binary Model for the Heartbeat Star System KIC 4142768

NASA Astrophysics Data System (ADS)

Manuel, Joseph; Hambleton, Kelly

2018-01-01

Heartbeat stars are a class of eccentric (e > 0.2) binary systems that undergo strong tidal forces. These tidal forces cause the shape of each star and the temperature across the stellar surfaces to change. This effect also generates variations in the light curve in the form of tidally-induced pulsations, which are theorized to have a significant effect on the circularization of eccentric orbits (Zahn, 1975). Using the binary modeling software PHOEBE (Prša & Zwitter 2005) on the Kepler photometric data and Keck radial velocity data for the eclipsing, heartbeat star KIC 4142768, we have determined the fundamental parameters including masses and radii. The frequency analysis of the residual data has surprisingly revealed approximately 29 pulsations with 8 being Delta Scuti pulsations, 10 being Gamma Doradus pulsations, and 11 being tidally-induced pulsations. After subtracting an initial binary model from the original, detrended photometric data, we analyzed the pulsation frequencies in the residual data. We then were able to disentangle the identified pulsations from the original data in order to conduct subsequent binary modeling. We plan to continue this study by applying asteroseismology to KIC 4142768. Through our continued investigation, we hope to extract information about the star’s internal structure and expect this will yield additional, interesting results.

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

Statistical Properties of Galactic δ Scuti Stars: Revisited

NASA Astrophysics Data System (ADS)

Chang, S.-W.; Protopapas, P.; Kim, D.-W.; Byun, Y.-I.

2013-05-01

We present statistical characteristics of 1578 δ Scuti stars including nearby field stars and cluster member stars within the Milky Way. We obtained 46% of these stars (718 stars) from work by Rodríguez and collected the remaining 54% of stars (860 stars) from other literature. We updated the entries with the latest information of sky coordinates, color, rotational velocity, spectral type, period, amplitude, and binarity. The majority of our sample is well characterized in terms of typical period range (0.02-0.25 days), pulsation amplitudes (<0.5 mag), and spectral types (A-F type). Given this list of δ Scuti stars, we examined relations between their physical properties (i.e., periods, amplitudes, spectral types, and rotational velocities) for field stars and cluster members, and confirmed that the correlations of properties are not significantly different from those reported in Rodríguez's work. All the δ Scuti stars are cross-matched with several X-ray and UV catalogs, resulting in 27 X-ray and 41 UV-only counterparts. These counterparts are interesting targets for further study because of their uniqueness in showing δ Scuti-type variability and X-ray/UV emission at the same time. The compiled catalog can be accessed through the Web interface http://stardb.yonsei.ac.kr/DeltaScuti.

The nature of EU Pegasi: An Algol-type binary with a δ Scuti-type component

NASA Astrophysics Data System (ADS)

Yang, Yuangui; Yuan, Huiyu; Dai, Haifeng; Zhang, Xiliang

2018-03-01

The comprehensive photometry and spectroscopy for the neglected eclipsing binary EU Pegasi are presented. We determine its spectral type to be A3V. With the W-D program, the photometric solution was deduced from the four-color light curves. The results imply that EU Peg is a detached binary with a mass ratio of q = 0.3105(± 0.0011), whose components nearly fill their Roche lobes. The low-amplitude pulsation occurs around the secondary eclipse, which may be attributed to the more massive component. Three frequencies are preliminarily explored by the Fourier analysis. The pulsating frequency at f1 = 34.1 c d-1 is a p-mode pulsation. The orbital period may be undergoing a secular decrease, superimposed by a cyclic variation. The period decreases at a rate of dP/dt = -7.34 ± 1.06 d yr-1, which may be attributed to mass loss from the system due to stellar wind. The cyclic oscillation, with Pmod = 31.0 ± 1.4 yr and A = 0.0054 ± 0.0010 d, may be caused by the light-time effect due to the assumed third body. With its evolution, the pulsating binary EU Peg will evolve from the detached configuration to the semi-detached case.

Four new Delta Scuti stars

NASA Technical Reports Server (NTRS)

Schutt, R. L.

1991-01-01

Four new Delta Scuti stars are reported. Power, modified into amplitude, spectra, and light curves are used to determine periodicities. A complete frequency analysis is not performed due to the lack of a sufficient time base in the data. These new variables help verify the many predictions that Delta Scuti stars probably exist in prolific numbers as small amplitude variables. Two of these stars, HR 4344 and HD 107513, are possibly Am stars. If so, they are among the minority of variable stars which are also Am stars.

Estrellas variables en campos de cúmulos abiertos galácticos detectadas en el relevamiento VVV

NASA Astrophysics Data System (ADS)

Palma, T.; Dékany, I.; Clariá, J. J.; Minniti, D.; Alonso-García, J. A.; Ramírez Alegría, S.; Bonatto, C.

2016-08-01

The present project constitutes a massive search for variable stars in the field of open clusters projected on highly reddened regions of the galactic disk and bulge. This search is being performed using -, - and -band observations of the near-infrared variability Survey Vista variables in the Via Lactea. We present the first results obtained in four open clusters projected on the Galactic bulge. The new variables discovered in the current work, 182 in total, are classified on the basis of their light curves and their locations in the corresponding color-magnitude diagrams. Among the newly discovered variable stars, Cepheids, RR Lyrae, Scuti, eclipsing binaries and other types have been found.

Asteroseismology of hybrid δ Scuti-γ Doradus pulsating stars

NASA Astrophysics Data System (ADS)

Sánchez Arias, J. P.; Córsico, A. H.; Althaus, L. G.

2017-01-01

Context. Hybrid δ Scuti-γ Doradus pulsating stars show acoustic (p) oscillation modes typical of δ Scuti variable stars, and gravity (g) pulsation modes characteristic of γ Doradus variable stars simultaneously excited. Observations from space missions such as MOST, CoRoT, and Kepler have revealed a large number of hybrid δ Scuti-γ Doradus pulsators, thus paving the way for an exciting new channel of asteroseismic studies. Aims: We perform detailed asteroseismological modelling of five hybrid δ Scuti-γ Doradus stars. Methods: A grid-based modeling approach was employed to sound the internal structure of the target stars using stellar models ranging from the zero-age main sequence to the terminal-age main sequence, varying parameters such as stellar mass, effective temperature, metallicity and core overshooting. Their adiabatic radial (ℓ = 0) and non-radial (ℓ = 1,2,3) p and g mode periods were computed. Two model-fitting procedures were used to search for asteroseismological models that best reproduce the observed pulsation spectra of each target star. Results: We derive the fundamental parameters and the evolutionary status of five hybrid δ Scuti-γ Doradus variable stars recently observed by the CoRoT and Kepler space missions: CoRoT 105733033, CoRoT 100866999, KIC 11145123, KIC 9244992, and HD 49434. The asteroseismological model for each star results from different criteria of model selection, in which we take full advantage of the richness of periods that characterises the pulsation spectra for this kind of star.

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

Chang, S.-W.; Kim, D.-W.; Byun, Y.-I.

We present statistical characteristics of 1578 {delta} Scuti stars including nearby field stars and cluster member stars within the Milky Way. We obtained 46% of these stars (718 stars) from work by Rodriguez and collected the remaining 54% of stars (860 stars) from other literature. We updated the entries with the latest information of sky coordinates, color, rotational velocity, spectral type, period, amplitude, and binarity. The majority of our sample is well characterized in terms of typical period range (0.02-0.25 days), pulsation amplitudes (<0.5 mag), and spectral types (A-F type). Given this list of {delta} Scuti stars, we examined relationsmore » between their physical properties (i.e., periods, amplitudes, spectral types, and rotational velocities) for field stars and cluster members, and confirmed that the correlations of properties are not significantly different from those reported in Rodriguez's work. All the {delta} Scuti stars are cross-matched with several X-ray and UV catalogs, resulting in 27 X-ray and 41 UV-only counterparts. These counterparts are interesting targets for further study because of their uniqueness in showing {delta} Scuti-type variability and X-ray/UV emission at the same time. The compiled catalog can be accessed through the Web interface http://stardb.yonsei.ac.kr/DeltaScuti.« less

The EPOCH Project. I. Periodic variable stars in the EROS-2 LMC database

NASA Astrophysics Data System (ADS)

Kim, Dae-Won; Protopapas, Pavlos; Bailer-Jones, Coryn A. L.; Byun, Yong-Ik; Chang, Seo-Won; Marquette, Jean-Baptiste; Shin, Min-Su

2014-06-01

The EPOCH (EROS-2 periodic variable star classification using machine learning) project aims to detect periodic variable stars in the EROS-2 light curve database. In this paper, we present the first result of the classification of periodic variable stars in the EROS-2 LMC database. To classify these variables, we first built a training set by compiling known variables in the Large Magellanic Cloud area from the OGLE and MACHO surveys. We crossmatched these variables with the EROS-2 sources and extracted 22 variability features from 28 392 light curves of the corresponding EROS-2 sources. We then used the random forest method to classify the EROS-2 sources in the training set. We designed the model to separate not only δ Scuti stars, RR Lyraes, Cepheids, eclipsing binaries, and long-period variables, the superclasses, but also their subclasses, such as RRab, RRc, RRd, and RRe for RR Lyraes, and similarly for the other variable types. The model trained using only the superclasses shows 99% recall and precision, while the model trained on all subclasses shows 87% recall and precision. We applied the trained model to the entire EROS-2 LMC database, which contains about 29 million sources, and found 117 234 periodic variable candidates. Out of these 117 234 periodic variables, 55 285 have not been discovered by either OGLE or MACHO variability studies. This set comprises 1906 δ Scuti stars, 6607 RR Lyraes, 638 Cepheids, 178 Type II Cepheids, 34 562 eclipsing binaries, and 11 394 long-period variables. catalog of these EROS-2 LMC periodic variable stars is available at http://stardb.yonsei.ac.kr and at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/566/A43

Multimode delta Scuti stars in the open cluster NGC 7062

NASA Astrophysics Data System (ADS)

Freyhammer, L. M.; Arentoft, T.; Sterken, C.

2001-03-01

The central field of NGC 7062 was observed intensively with the main goal of finding delta Scuti stars suitable for use in asteroseismological tests of stellar structure and evolution theory. BV time series photometry was obtained for this northern open cluster, which has a large population of stars inside the delta Scuti instability strip, making it a probable host of several such variables. We report findings of 15 pulsating stars, including at least 13 delta Scuti stars. Ten variables oscillate in two or more frequencies. Only one of these variables was known before, for which we detected 9 frequencies. Five probable variables are mentioned, and period analysis is given for all 20 stars. Based on observations obtained at the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisíca de Canarias.

The Molybdenum titanium Phase Diagram Evaluated from Ab initio Calculations

DTIC Science & Technology

2016-10-07

thermodynamic properties of this binary system are not well known and two conflicting descriptions of the β-phase stability have been presented in the...computational thermodynamics CALPHAD approach [13] and the Thermo-Calc software [14]. These studies led to two conflicting descriptions of the stability of...energy calculations, with an energy cutoff separating core and valence states of -6 Ry. 2.2. Thermodynamic modeling The formation enthalpy of a

uvby photometry of theta Tucanae

NASA Astrophysics Data System (ADS)

Sterken, C.; Spoon, H.

2017-12-01

theta Tucanae (HR 139, V=6.11, A7 IV) is a binary with a delta Scuti primary that was the subject of several photometric monitoring campaigns during the 1970s and again in the 1990s. The data presented in this paper were collected during an observing campaign from mid-September to the end of October 1993 at ESO La Silla, Chile, using the simultaneous Stroemgren uvby photometer at the SAT telescope during 25 partial nights. We present a time series of 1432 four-colour extinction-corrected magnitudes in the SAT instrumental system. This collection of data forms a homogeneous and contiguous dataset, obtained in one single instrumental setup, at one single observing site using one single observing protocol, and with centralized data reduction.

Technical Communications in Urban Operations (Les communications techniques en operations urbaines)

DTIC Science & Technology

2010-09-01

SCUTI – Scuola Trasmissioni ed Informatica dell’Esercito Italiano Via dei Genieri, 287, 00143-Roma Cecchignola Email: Mario.DiStefano@selex...comms.com Lt. Fabrizio LAMBIASE SCUTI – Scuola Trasmissioni ed Informatica dell’Esercito Italiano Via dei Genieri, 287, 00143 Roma Cecchignola

A Preliminary Survey of Short Time-Scale Optical Variables with ROTSE

NASA Astrophysics Data System (ADS)

McKay, T.; Akerlof, C.; Balsano, R.; Bloch, J.; Casperson, D.; Gisler, G.; Kehoe, R.; Lee, B.; Marshall, S.; Rykoff, E.; Smith, D. A.; Szymanski, J.; Wren, J.; ROTSE Collaboration

2000-12-01

We have performed a preliminary optical survey of short timescale variability with the ROTSE-I telephoto array. The data sample is divided into two parts. The first is a survey of 256 square degrees ( 120k sources) imaged every 80 s for a cumulative 20 hrs to a sensitivity of approximately magnitude 15.5. The second is a similarly sensitive survey of 512 square degrees ( 250k sources) imaged every 80 s (with 7 minute gaps) for a total of approximately 60 hrs. A further 0.4 mag. increase in sensitivity is obtained by co-adding these frames in pairs. We have identified a variety of new variable stars in this sample, including many Delta Scuti stars and contact binaries. Preliminary characterization of these sources will be presented.

THE TAIWAN-AMERICAN OCCULTATION SURVEY PROJECT STELLAR VARIABILITY. I. DETECTION OF LOW-AMPLITUDE {delta} SCUTI STARS

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

Kim, D.-W.; Protopapas, P.; Alcock, C.

2010-02-15

We analyzed data accumulated during 2005 and 2006 by the Taiwan-American Occultation Survey (TAOS) in order to detect short-period variable stars (periods of {approx}<1 hr) such as {delta} Scuti. TAOS is designed for the detection of stellar occultation by small-size Kuiper Belt Objects and is operating four 50 cm telescopes at an effective cadence of 5 Hz. The four telescopes simultaneously monitor the same patch of the sky in order to reduce false positives. To detect short-period variables, we used the fast Fourier transform algorithm (FFT) in as much as the data points in TAOS light curves are evenly spaced.more » Using FFT, we found 41 short-period variables with amplitudes smaller than a few hundredths of a magnitude and periods of about an hour, which suggest that they are low-amplitude {delta} Scuti stars. The light curves of TAOS {delta} Scuti stars are accessible online at the Time Series Center Web site (http://timemachine.iic.harvard.edu)« less

Searching for δ Scuti-type pulsation and characterising northern pre-main-sequence field stars

NASA Astrophysics Data System (ADS)

Díaz-Fraile, D.; Rodríguez, E.; Amado, P. J.

2014-08-01

Context. Pre-main-sequence (PMS) stars are objects evolving from the birthline to the zero-age main sequence (ZAMS). Given a mass range near the ZAMS, the temperatures and luminosities of PMS and main-sequence stars are very similar. Moreover, their evolutionary tracks intersect one another causing some ambiguity in the determination of their evolutionary status. In this context, the detection and study of pulsations in PMS stars is crucial for differentiating between both types of stars by obtaining information of their interiors via asteroseismic techniques. Aims: A photometric variability study of a sample of northern field stars, which previously classified as either PMS or Herbig Ae/Be objects, has been undertaken with the purpose of detecting δ Scuti-type pulsations. Determination of physical parameters for these stars has also been carried out to locate them on the Hertzsprung-Russell diagram and check the instability strip for this type of pulsators. Methods: Multichannel photomultiplier and CCD time series photometry in the uvby Strömgren and BVI Johnson bands were obtained during four consecutive years from 2007 to 2010. The light curves have been analysed, and a variability criterion has been established. Among the objects classified as variable stars, we have selected those which present periodicities above 4 d-1, which was established as the lowest limit for δ Scuti-type pulsations in this investigation. Finally, these variable stars have been placed in a colour-magnitude diagram using the physical parameters derived with the collected uvbyβ Strömgren-Crawford photometry. Results: Five PMS δ Scuti- and three probable β Cephei-type stars have been detected. Two additional PMS δ Scuti stars are also confirmed in this work. Moreover, three new δ Scuti- and two γ Doradus-type stars have been detected among the main-sequence objects used as comparison or check stars.

RED GIANTS IN ECLIPSING BINARY AND MULTIPLE-STAR SYSTEMS: MODELING AND ASTEROSEISMIC ANALYSIS OF 70 CANDIDATES FROM KEPLER DATA

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

Gaulme, P.; McKeever, J.; Rawls, M. L.

2013-04-10

Red giant stars are proving to be an incredible source of information for testing models of stellar evolution, as asteroseismology has opened up a window into their interiors. Such insights are a direct result of the unprecedented data from space missions CoRoT and Kepler as well as recent theoretical advances. Eclipsing binaries are also fundamental astrophysical objects, and when coupled with asteroseismology, binaries provide two independent methods to obtain masses and radii and exciting opportunities to develop highly constrained stellar models. The possibility of discovering pulsating red giants in eclipsing binary systems is therefore an important goal that could potentiallymore » offer very robust characterization of these systems. Until recently, only one case has been discovered with Kepler. We cross-correlate the detected red giant and eclipsing-binary catalogs from Kepler data to find possible candidate systems. Light-curve modeling and mean properties measured from asteroseismology are combined to yield specific measurements of periods, masses, radii, temperatures, eclipse timing variations, core rotation rates, and red giant evolutionary state. After using three different techniques to eliminate false positives, out of the 70 systems common to the red giant and eclipsing-binary catalogs we find 13 strong candidates (12 previously unknown) to be eclipsing binaries, one to be a non-eclipsing binary with tidally induced oscillations, and 10 more to be hierarchical triple systems, all of which include a pulsating red giant. The systems span a range of orbital eccentricities, periods, and spectral types F, G, K, and M for the companion of the red giant. One case even suggests an eclipsing binary composed of two red giant stars and another of a red giant with a {delta}-Scuti star. The discovery of multiple pulsating red giants in eclipsing binaries provides an exciting test bed for precise astrophysical modeling, and follow-up spectroscopic observations of many of the candidate systems are encouraged. The resulting highly constrained stellar parameters will allow, for example, the exploration of how binary tidal interactions affect pulsations when compared to the single-star case.« less

A Study of Chemical Composition of δ Scuti-Type Stars Based on the Observations with the BTA and RTT-150

NASA Astrophysics Data System (ADS)

Galeev, A. I.; Berdnikova, V. M.; Ivanova, D. V.; Kudryavtsev, D. O.; Shimanskaya, N. N.; Shimansky, V. V.; Balashova, M. O.

2017-06-01

The results of a study of a sample of δ Scuti-type stars obtained from the observations with the BTA and RTT-150 are presented. Based on photometric data, we measured and analyzed the fundamental parameters of all the studied stars. For eight stars (for two of them for the first time), the fundamental parameters of the atmospheres (Teff, log g, [Fe/H]) and the chemical composition for 29 elements in the LTE-approximation are received using spectroscopic observations. The chemical composition analysis demonstrates both the solar abundances of chemical elements and the anomalies of chemical composition typical of Am stars in the studied sample of δ Scuti-type stars.

The moderately interacting Algol-type eclipsing binary RY Geminorum

NASA Technical Reports Server (NTRS)

Plavec, Mirek J.; Dobias, Jan J.

1987-01-01

Ultraviolet spectra of the Algol-type semidetached system RY Geminorum, whose components can be described as A0 V and K0 IV, have been matched to the ultraviolet spectrum by Kurucz (1979) model atmospheres, and a best fit is found for T(eff) = 9150 K. Comparison with standard star spectra requires that this value be raised to 9400 K. The color excess of the system is determined to be no more than E(B-V) = 0.03 mag; the distance to the system is about 360 pc. The masses are approximately 2.36 and 0.38 solar masses, and the radii are 2.5 and 5.8 solar radii, respectively. The separation of the two centers is 26 solar radii. Evidence for a circumstellar line absorption is found in optical and ultraviolet spectrograms, and evidence is found in IUE spectra taken in partial eclipse for circumstellar emission lines of the type detected previously in the WS Serpentis stars and in several semidetected systems of the Algol type.

High-resolution spectroscopy and abundance analysis of δ Scuti stars near the γ Doradus instability strip

NASA Astrophysics Data System (ADS)

Kahraman Aliçavuş, F.; Niemczura, E.; Polińska, M.; Hełminiak, K. G.; Lampens, P.; Molenda-Żakowicz, J.; Ukita, N.; Kambe, E.

2017-10-01

δ Scuti stars are remarkable objects for asteroseismology. In spite of decades of investigations, there are still important questions about these pulsating stars to be answered, such as their positions in log Teff-log g diagram, or the dependence of the pulsation modes on atmospheric parameters and rotation. Therefore, we performed a detailed spectroscopic study of 41 δ Scuti stars. The selected objects are located near the γ Doradus instability strip to make a reliable comparison between both types of variables. Spectral classification, stellar atmospheric parameters (Teff, log g, ξ) and v sin I values were determined. The spectral types and luminosity classes of stars were found to be A1-F5 and III-V, respectively. The Teff ranges from 6600 to 9400 K, whereas the obtained log g values are from 3.4 to 4.3. The v sin I values were found between 10 and 222 km s-1. The derived chemical abundances of δ Scuti stars were compared to those of the non-pulsating stars and γ Doradus variables. It turned out that both δ Scuti and γ Doradus variables have similar abundance patterns, which are slightly different from the non-pulsating stars. These chemical differences can help us to understand why there are non-pulsating stars in classical instability strip. Effects of the obtained parameters on pulsation period and amplitude were examined. It appears that the pulsation period decreases with increasing Teff. No significant correlations were found between pulsation period, amplitude and v sin I.

The type specimens of Tenthredo Linnaeus, 1758 (Hymenoptera: Tenthredinidae) deposited in the Hungarian Natural History Museum.

PubMed

Taeger, Andreas

2013-01-01

The type specimens of Tenthredo sensu lato deposited in the Hungarian Natural History Museum (Budapest) are reviewed. The following synonyms are recognized and discussed: Rhogogastera aenescens Mocsáry, 1909, syn. nov. of Tenthredo (Temuledo) finschi finschi W.F. Kirby, 1882; Macrophya prasinipes Konow, 1891, syn. nov. of Macrophya caucasica (Mocsáry, 1880); Tenthredo concinnoides Malaise, 1945, syn. nov. of Tenthredo concinna Mocsáry, 1883; Tenthredo fulviventris Mocsáry, 1909, syn. nov. of Tenthredo (Tenthredella) crenata (Enslin, 1912); Tenthredo vespa inaffectata Muche, 1965, syn. nov. of Tenthredo (Tenthredo) vespa Retzius, 1783; Rhogogaster kaszabi Zombori, 1973, syn. nov. of Tenthredo (Eurogaster) aaliensis (Strand, 1898); Tenthredo kaszabi Muche, 1965, syn. nov. of Tenthredo (Eurogaster) mesomela Linné, 1758; Rhogogastera opacella Mocsáry, 1909, syn. nov. of Tenthredo (Eurogaster) stulta Jakowlew, 1891; Tenthredo tschinggischanensis Muche, 1965 syn. nov. of Tenthredo (Tenthredella) balteata Klug, 1817; Tenthredo unfasciata Mocsáry, 1909, syn. nov. of Tenthredo (Tenthredella) colon Klug, 1817; Tenthredella cucullata Enslin, 1912, syn. nov. of Tenthredo (Tenthredella) colon Klug, 1817. Macrophya caucasica (Mocsáry, 1880) is a new combination (comb. nov.) for Allantus caucasicus Mocsáry, 1880. Tenthredo semicolon Mol, is a replacement name (nom. nov.) for Tenthredo punctulata Konow, 1887, nom. praeocc., nec Klug, 1817. Tenthredo chanae Taeger & Shinohara spec. nov., a species close to Tenthredo concinna, is described from Taiwan. Lectotypes are designated and illustrated for the following 30 nominal taxa: Rhogogastera aenescens Mocsáry, 1909; Allantus albiventris Mocsáry, 1880; Allantus almasyanus Mocsáry, 1909; Macrophya binaculata Mocsáry, 1909; Allantus brachycerus Mocsáry, 1909; Allantus caucasicus Mocsáry, 1880; Allantus centrorufus Mocsáry, 1909; Tenthredo chyzeri Mocsáry, 1891; Tenthredo concinna Mocsáry, 1883; Tenthredo concinnoides Malaise, 1945; Allantus eburneus Mocsáry, 1909; Allantus eburneus Mocsáry, 1909; Allantus fulvicornis Mocsáry, 1909; Tenthredo fulvicornis Mocsáry, 1909; Allantus fulvipennis Mocsáry, 1909; Tenthredo fulviventris Mocsáry, 1909; Tenthredo gribodoi Konow, 1898; Allantus lateralis Mocsáry, 1909; Allantus limbiferus Mocsáry, 1891; Allantus moestus Mocsáry, 1883; Rhogogastera nigrita Mocsáry, 1909; Allantus obesus Mocsáry, 1880; Macrophya prasinipes Konow, 1891; Tenthredo punctulata Konow, 1887; Allantus rufipes Mocsáry, 1909; Allantus sabariensis Mocsáry, 1880; Allantus sanguinolentus Mocsáry, 1909; Allantus temulus var. scutellatus Mocsáry, 1909; Allantus testaceus Mocsáry, 1909; Allantus variabilis Mocsáry, 1909. The first records of Tenthredo concinna for Vietnam and Nepal are given.

The EB factory project. I. A fast, neural-net-based, general purpose light curve classifier optimized for eclipsing binaries

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

Paegert, Martin; Stassun, Keivan G.; Burger, Dan M.

2014-08-01

We describe a new neural-net-based light curve classifier and provide it with documentation as a ready-to-use tool for the community. While optimized for identification and classification of eclipsing binary stars, the classifier is general purpose, and has been developed for speed in the context of upcoming massive surveys such as the Large Synoptic Survey Telescope. A challenge for classifiers in the context of neural-net training and massive data sets is to minimize the number of parameters required to describe each light curve. We show that a simple and fast geometric representation that encodes the overall light curve shape, together withmore » a chi-square parameter to capture higher-order morphology information results in efficient yet robust light curve classification, especially for eclipsing binaries. Testing the classifier on the ASAS light curve database, we achieve a retrieval rate of 98% and a false-positive rate of 2% for eclipsing binaries. We achieve similarly high retrieval rates for most other periodic variable-star classes, including RR Lyrae, Mira, and delta Scuti. However, the classifier currently has difficulty discriminating between different sub-classes of eclipsing binaries, and suffers a relatively low (∼60%) retrieval rate for multi-mode delta Cepheid stars. We find that it is imperative to train the classifier's neural network with exemplars that include the full range of light curve quality to which the classifier will be expected to perform; the classifier performs well on noisy light curves only when trained with noisy exemplars. The classifier source code, ancillary programs, a trained neural net, and a guide for use, are provided.« less

Unexpected series of regular frequency spacing of δ Scuti stars in the non-asymptotic regime. II. Sample-Echelle diagrams and rotation

DOE PAGES

Paparo, M.; Benko, J. M.; Hareter, M.; ...

2016-06-17

A sequence search method was developed for searching for regular frequency spacing in δ Scuti stars by visual inspection (VI) and algorithmic search. The sample contains 90 δ Scuti stars observed by CoRoT. An example is given to represent the VI. The algorithm (SSA) is described in detail. The data treatment of the CoRoT light curves, the criteria for frequency filtering, and the spacings derived by two methods (i.e., three approaches: VI, SSA, and FT) are given for each target. Echelle diagrams are presented for 77 targets for which at least one sequence of regular spacing was identified. Comparing the spacing and the shifts between pairs of echelle ridges revealed that at least one pair of echelle ridges is shifted to midway between the spacing for 22 stars. The estimated rotational frequencies compared to the shifts revealed rotationally split doublets, triplets, and multiplets not only for single frequencies, but for the complete echelle ridges in 31 δ Scuti stars. Furthermore, using several possible assumptions for the origin of the spacings, we derived the large separation (more » $${\\rm{\\Delta }}\

Unexpected series of regular frequency spacing of δ Scuti stars in the non-asymptotic regime. II. Sample-Echelle diagrams and rotation

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

Paparo, M.; Benko, J. M.; Hareter, M.

A sequence search method was developed for searching for regular frequency spacing in δ Scuti stars by visual inspection (VI) and algorithmic search. The sample contains 90 δ Scuti stars observed by CoRoT. An example is given to represent the VI. The algorithm (SSA) is described in detail. The data treatment of the CoRoT light curves, the criteria for frequency filtering, and the spacings derived by two methods (i.e., three approaches: VI, SSA, and FT) are given for each target. Echelle diagrams are presented for 77 targets for which at least one sequence of regular spacing was identified. Comparing the spacing and the shifts between pairs of echelle ridges revealed that at least one pair of echelle ridges is shifted to midway between the spacing for 22 stars. The estimated rotational frequencies compared to the shifts revealed rotationally split doublets, triplets, and multiplets not only for single frequencies, but for the complete echelle ridges in 31 δ Scuti stars. Furthermore, using several possible assumptions for the origin of the spacings, we derived the large separation (more » $${\\rm{\\Delta }}\

VizieR Online Data Catalog: BVI photometry of LMC bar variables (Di Fabrizio+, 2005)

NASA Astrophysics Data System (ADS)

di Fabrizio, L.; Clementini, G.; Maio, M.; Bragaglia, A.; Carretta, E.; Gratton, R.; Montegriffo, P.; Zoccali, M.

2005-01-01

We present the Johnson-Cousins B,V and I time series data obtained for 162 variable stars (135 RR Lyrae, 4 candidate Anomalous Cepheids, 11 Classical Cepheids, 11 eclipsing binaries and 1 delta Scuti star) in two 13x13 square arcmin areas close to the bar of the Large Magellanic Cloud. The photometric observations presented in this paper were carried out at the 1.54m Danish telescope located in La Silla, Chile, on the nights 4-7 January 1999, UT, and 23-24 January 2001, UT, respectively. In the paper we give coordinates, finding charts, periods, epochs, amplitudes, and mean quantities (intensity- and magnitude-averaged luminosities) of the variables with full coverage of the light variations, along with a discussion of the pulsation properties of the RR Lyrae stars in the sample. (8 data files).

Impact of gaps in the asteroseismic characterization of pulsating stars. I. The efficiency of pre-whitening

NASA Astrophysics Data System (ADS)

Pascual-Granado, J.; Suárez, J. C.; Garrido, R.; Moya, A.; Hernández, A. García; Rodón, J. R.; Lares-Martiz, M.

2018-06-01

Context. It is known that the observed distribution of frequencies in CoRoT and Kepler δ Scuti stars has no parallelism with any theoretical model. Pre-whitening is a widespread technique in the analysis of time series with gaps from pulsating stars located in the classical instability strip, such as δ Scuti stars. However, some studies have pointed out that this technique might introduce biases in the results of the frequency analysis. Aims: This work aims at studying the biases that can result from pre-whitening in asteroseismology. The results will depend on the intrinsic range and distribution of frequencies of the stars. The periodic nature of the gaps in CoRoT observations, only in the range of the pulsational frequency content of the δ Scuti stars, is shown to be crucial to determining their oscillation frequencies, the first step in performing asteroseismology of these objects. Hence, here we focus on the impact of pre-whitening on the asteroseismic characterization of δ Scuti stars. Methods: We select a sample of 15 δ Scuti stars observed by the CoRoT satellite, for which ultra-high-quality photometric data have been obtained by its seismic channel. In order to study the impact on the asteroseismic characterization of δ Scuti stars we perform the pre-whitening procedure on three datasets: gapped data, linearly interpolated data, and data with gaps interpolated using Autoregressive and Moving Average models (ARMA). Results: The different results obtained show that at least in some cases pre-whitening is not an efficient procedure for the deconvolution of the spectral window. Therefore, in order to reduce the effect of the spectral window to a minimum, in addition to performing a pre-whitening of the data, it is necessary to interpolate with an algorithm that is aimed to preserve the original frequency content. Tables 5-49 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/614/A40

Classification of ROTSE Variable Stars using Machine Learning

NASA Astrophysics Data System (ADS)

Wozniak, P. R.; Akerlof, C.; Amrose, S.; Brumby, S.; Casperson, D.; Gisler, G.; Kehoe, R.; Lee, B.; Marshall, S.; McGowan, K. E.; McKay, T.; Perkins, S.; Priedhorsky, W.; Rykoff, E.; Smith, D. A.; Theiler, J.; Vestrand, W. T.; Wren, J.; ROTSE Collaboration

2001-12-01

We evaluate several Machine Learning algorithms as potential tools for automated classification of variable stars. Using the ROTSE sample of ~1800 variables from a pilot study of 5% of the whole sky, we compare the effectiveness of a supervised technique (Support Vector Machines, SVM) versus unsupervised methods (K-means and Autoclass). There are 8 types of variables in the sample: RR Lyr AB, RR Lyr C, Delta Scuti, Cepheids, detached eclipsing binaries, contact binaries, Miras and LPVs. Preliminary results suggest a very high ( ~95%) efficiency of SVM in isolating a few best defined classes against the rest of the sample, and good accuracy ( ~70-75%) for all classes considered simultaneously. This includes some degeneracies, irreducible with the information at hand. Supervised methods naturally outperform unsupervised methods, in terms of final error rate, but unsupervised methods offer many advantages for large sets of unlabeled data. Therefore, both types of methods should be considered as promising tools for mining vast variability surveys. We project that there are more than 30,000 periodic variables in the ROTSE-I data base covering the entire local sky between V=10 and 15.5 mag. This sample size is already stretching the time capabilities of human analysts.

AR Sco: the first white dwarf pulsar?

NASA Astrophysics Data System (ADS)

Gaensicke, Boris

2015-10-01

AR Sco was mis-classified in 1971 as a pulsating delta-Scuti star, and has received little attention until now. In May this year, we became aware of the truly unique nature of this object: besides a two-magnitude modulation on the 3.56h orbital period, we detected a coherent 2min variability from the optical into the radio, and a spectacular infrared excess across the WISE bands. Our optical spectroscopy reveals a late-type companion star, clearly identifying AR Sco as a compact binary. While most of its observational characteristics are reminiscent of neutron star or black hole binaries, the 2min modulation is archetypical of the spin period of a strongly magnetic white dwarf. We believe that AR Sco is the first white dwarf radio pulsar, where the combination of a large field and rapid rotation results in the acceleration of relativisitic particles that blast the inner hemisphere of the M-dwarf companion, akin to the well-known milli-second pulsars. The ultimate proof of our hypothesis relies on the unambiguous identification of the white dwarf, which will be achieved through the detection of Zeeman-split Ly alpha absorption in the requested COS/G140L observations.

New variable stars discovered in the fields of three Galactic open clusters using the VVV survey

NASA Astrophysics Data System (ADS)

Palma, T.; Minniti, D.; Dékány, I.; Clariá, J. J.; Alonso-García, J.; Gramajo, L. V.; Ramírez Alegría, S.; Bonatto, C.

2016-11-01

This project is a massive near-infrared (NIR) search for variable stars in highly reddened and obscured open cluster (OC) fields projected on regions of the Galactic bulge and disk. The search is performed using photometric NIR data in the J-, H- and Ks- bands obtained from the Vista Variables in the Vía Láctea (VVV) Survey. We performed in each cluster field a variability search using Stetson's variability statistics to select the variable candidates. Later, those candidates were subjected to a frequency analysis using the Generalized Lomb-Scargle and the Phase Dispersion Minimization algorithms. The number of independent observations range between 63 and 73. The newly discovered variables in this study, 157 in total in three different known OCs, are classified based on their light curve shapes, periods, amplitudes and their location in the corresponding color-magnitude (J -Ks ,Ks) and color-color (H -Ks , J - H) diagrams. We found 5 possible Cepheid stars which, based on the period-luminosity relation, are very likely type II Cepheids located behind the bulge. Among the newly discovered variables, there are eclipsing binaries, δ Scuti, as well as background RR Lyrae stars. Using the new version of the Wilson & Devinney code as well as the "Physics Of Eclipsing Binaries" (PHOEBE) code, we analyzed some of the best eclipsing binaries we discovered. Our results show that these studied systems turn out to be ranging from detached to double-contact binaries, with low eccentricities and high inclinations of approximately 80°. Their surface temperatures range between 3500 K and 8000 K.

Pulsation, binarity and close frequency spacing in $delta Scuti ta$ Scuti stars: BQ and BW Cancri. Results of the STEPHI VI campaign in Praesepe Cluster

NASA Astrophysics Data System (ADS)

Alvarez, M.; Hernandez, M. M.; Michel, E.; Jiang, S. Y.; Belmonte, J. A.; Chevreton, M.; Massacrier, G.; Liu, Y. Y.; Li, Z. P.; Goupil, M. J.; Cortes, T. Roca; Mangeney, A.; Dolez, N.; Valtier, J. C.; Vidal, I.; Sperl, M.; Talon, S.

1998-12-01

New pulsation modes in two delta Scuti stars of Praesepe cluster, BQ and BW Cnc, have been detected during the STEPHI VI campaign in 1995. In particular, 3 frequencies for BQ Cnc and 9 frequencies for BW Cnc have been found above a 99% confidence level. The possibility of the presence of a g-mode present in BQ Cnc is discussed, considering its binarity. The effect of mutual interference between very close detected frequencies in BW Cnc during the observations, is also considered. This last effect reveals the necessity of long-period observing runs, in order to avoid its influence in the final number of detected modes. In such situation, studies of secular amplitude changes can be strongly affected.

Population of the lower part of the instability strip: Delta Scuti stars and dwarf Cepheids (or AI Velorum)

NASA Technical Reports Server (NTRS)

Auvergne, M.; Baglin, A.; Lecontel, J. M.; Valtier, J. C.

1980-01-01

Some of the properties of the atmospheric variations in delta Scuti stars were investigated with emphasis on the amplitude and the shape of both light curves and radial velocity curves. It is shown that these curves are small and rapidly variable in the case of dwarf Scuti stars; for the evolved stars the situation is more complex. The relation between variables and nonvariables, and also the results on abundances in the atmospheres of these stars were surveyed with respect to the hydrodynamics of their envelopes. The abundance anomalies of Am stars were qualitatively examined. The coexistence of abundance anomalies and variability among giants were also studied. Attempts were made to relate the variability to the hydrogen ionization zone in an envelope deprived of helium. Specific results are reported.

Imperatoxin a enhances Ca(2+) release in developing skeletal muscle containing ryanodine receptor type 3.

PubMed Central

Nabhani, Thomas; Zhu, Xinsheng; Simeoni, Ilenia; Sorrentino, Vincenzo; Valdivia, Héctor H; García, Jesús

2002-01-01

Most adult mammalian skeletal muscles contain only one isoform of ryanodine receptor (RyR1), whereas neonatal muscles contain two isoforms (RyR1 and RyR3). Membrane depolarization fails to evoke calcium release in muscle cells lacking RyR1, demonstrating an essential role for this isoform in excitation-contraction coupling. In contrast, the role of RyR3 is unknown. We studied the participation of RyR3 in calcium release in wild type (containing both RyR1 and RyR3 isoforms) and RyR3-/- (containing only RyR1) myotubes in the presence or absence of imperatoxin A (IpTxa), a high-affinity agonist of ryanodine receptors. IpTxa significantly increased the amplitude and the rate of release only in wild-type myotubes. Calcium currents, recorded simultaneously with the transients, were not altered with IpTxa treatment. [(3)H]ryanodine binding to RyR1 or RyR3 was significantly increased in the presence of IpTxa. Additionally, IpTxa modified the gating and conductance level of single RyR1 or RyR3 channels when studied in lipid bilayers. Our data show that IpTxa can interact with both RyRs and that RyR3 is functional in myotubes and it can amplify the calcium release signal initiated by RyR1, perhaps through a calcium-induced mechanism. In addition, our data indicate that when RyR3-/- myotubes are voltage-clamped, the effect of IpTxa is not detected because RyR1s are under the control of the dihydropyridine receptor. PMID:11867448

VizieR Online Data Catalog: RV of candidate hybrid variable stars (Lampens+, 2018)

NASA Astrophysics Data System (ADS)

Lampens, P.; Fremat, Y.; Vermeylen, L.; Sodor, A.; Skarka, M.; De Cat, P.; Bognar, Zs.; de Nutte, R.; Dumortier, L.; Escorza, A.; Oomen, G. M.; van de Steene, G.; Kamath, D.; Laverick, M.; Samadi, A.; Triana, S.; Lehmann, H.

2017-09-01

We present the individual radial velocity measurements of 50 candidate delta Scuti - gamma Doradus hybrid stars and one delta Scuti star from the Kepler mission collected with the Hermes and Ace spectrographs over a time span of months to years. The radial velocities were measured using spectrum synthesis and a two-dimensional cross-correlation technique in the case of double- and triple-lined systems. (5 data files).

The effect of tides on self-driven stellar pulsations

NASA Astrophysics Data System (ADS)

Balona, L. A.

2018-06-01

In addition to rotation, a tidal force in a binary introduces another axis of symmetry joining the two centres of mass. If the stars are in circular orbit and synchronous rotation, a pulsation with spherical harmonic degree l is split into l + 1 frequencies. In the observer's frame of reference, these in turn are further split into equidistant frequencies spaced by multiples of the orbital frequency. In the periodogram of a pulsating star, tidal action can be seen as low-amplitude equidistant splitting of each oscillation mode which are not harmonics of the orbital frequency. This effect is illustrated using Kepler observations of the heartbeat variable, KIC 4142768, which is also a δ Scuti star. Even though the theory is only applicable to circular orbits, the expected equidistant splitting is clearly seen in all four of the highest amplitude modes. This results in amplitude variability of each pulsation mode with a period equal to the orbital period.

A radio-pulsing white dwarf binary star.

PubMed

Marsh, T R; Gänsicke, B T; Hümmerich, S; Hambsch, F-J; Bernhard, K; Lloyd, C; Breedt, E; Stanway, E R; Steeghs, D T; Parsons, S G; Toloza, O; Schreiber, M R; Jonker, P G; van Roestel, J; Kupfer, T; Pala, A F; Dhillon, V S; Hardy, L K; Littlefair, S P; Aungwerojwit, A; Arjyotha, S; Koester, D; Bochinski, J J; Haswell, C A; Frank, P; Wheatley, P J

2016-09-15

White dwarfs are compact stars, similar in size to Earth but approximately 200,000 times more massive. Isolated white dwarfs emit most of their power from ultraviolet to near-infrared wavelengths, but when in close orbits with less dense stars, white dwarfs can strip material from their companions and the resulting mass transfer can generate atomic line and X-ray emission, as well as near- and mid-infrared radiation if the white dwarf is magnetic. However, even in binaries, white dwarfs are rarely detected at far-infrared or radio frequencies. Here we report the discovery of a white dwarf/cool star binary that emits from X-ray to radio wavelengths. The star, AR Scorpii (henceforth AR Sco), was classified in the early 1970s as a δ-Scuti star, a common variety of periodic variable star. Our observations reveal instead a 3.56-hour period close binary, pulsing in brightness on a period of 1.97 minutes. The pulses are so intense that AR Sco's optical flux can increase by a factor of four within 30 seconds, and they are also detectable at radio frequencies. They reflect the spin of a magnetic white dwarf, which we find to be slowing down on a 10 7 -year timescale. The spin-down power is an order of magnitude larger than that seen in electromagnetic radiation, which, together with an absence of obvious signs of accretion, suggests that AR Sco is primarily spin-powered. Although the pulsations are driven by the white dwarf's spin, they mainly originate from the cool star. AR Sco's broadband spectrum is characteristic of synchrotron radiation, requiring relativistic electrons. These must either originate from near the white dwarf or be generated in situ at the M star through direct interaction with the white dwarf's magnetosphere.

Functional nonequality of the cardiac and skeletal ryanodine receptors.

PubMed

Nakai, J; Ogura, T; Protasi, F; Franzini-Armstrong, C; Allen, P D; Beam, K G

1997-02-04

Dihydropyridine receptors (DHPRs), which are voltage-gated Ca2+ channels, and ryanodine receptors (RyRs), which are intracellular Ca2+ release channels, are expressed in diverse cell types, including skeletal and cardiac muscle. In skeletal muscle, there appears to be reciprocal signaling between the skeletal isoforms of both the DHPR and the RyR (RyR-1), such that Ca2+ release activity of RyR-1 is controlled by the DHPR and Ca2+ channel activity of the DHPR is controlled by RyR-1. Dyspedic skeletal muscle cells, which do not express RyR-1, lack excitation-contraction coupling and have an approximately 30-fold reduction in L-type Ca2+ current density. Here we have examined the ability of the predominant cardiac and brain RyR isoform, RyR-2, to substitute for RyR-1 in interacting with the skeletal DHPR. When RyR-2 is expressed in dyspedic muscle cells, it gives rise to spontaneous intracellular Ca2+ oscillations and supports Ca2+ entry-induced Ca2+ release. However, unlike RyR-1, the expressed RyR-2 does not increase the Ca2+ channel activity of the DHPR, nor is the gating of RyR-2 controlled by the skeletal DHPR. Thus, the ability to participate in skeletal-type reciprocal signaling appears to be a unique feature of RyR-1.

Spectroscopy of γ Doradus stars

NASA Astrophysics Data System (ADS)

Brunsden, E.; Pollard, K. R.; Cottrell, P. L.; Wright, D. J.; De Cat, P.; Kilmartin, P. M.

2014-02-01

The musician programme at the University of Canterbury has been successfully identifying pulsation modes in many γ Doradus stars using hundreds of ground-based spectroscopic observations. This paper describes some of the successful mode identifications and emerging patterns of the programme. The hybrid γ Doradus/δ Scuti star HD 49434 remains an enigma, despite the analysis of more than 1700 multi-site high-resolution spectra. A new result for this star is apparently distinct line-profile variations for the γ Doradus and δ Scuti frequencies.

The fourfold way of the genetic code.

PubMed

Jiménez-Montaño, Miguel Angel

2009-11-01

We describe a compact representation of the genetic code that factorizes the table in quartets. It represents a "least grammar" for the genetic language. It is justified by the Klein-4 group structure of RNA bases and codon doublets. The matrix of the outer product between the column-vector of bases and the corresponding row-vector V(T)=(C G U A), considered as signal vectors, has a block structure consisting of the four cosets of the KxK group of base transformations acting on doublet AA. This matrix, translated into weak/strong (W/S) and purine/pyrimidine (R/Y) nucleotide classes, leads to a code table with mixed and unmixed families in separate regions. A basic difference between them is the non-commuting (R/Y) doublets: AC/CA, GU/UG. We describe the degeneracy in the canonical code and the systematic changes in deviant codes in terms of the divisors of 24, employing modulo multiplication groups. We illustrate binary sub-codes characterizing mutations in the quartets. We introduce a decision-tree to predict the mode of tRNA recognition corresponding to each codon, and compare our result with related findings by Jestin and Soulé [Jestin, J.-L., Soulé, C., 2007. Symmetries by base substitutions in the genetic code predict 2' or 3' aminoacylation of tRNAs. J. Theor. Biol. 247, 391-394], and the rearrangements of the table by Delarue [Delarue, M., 2007. An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices. RNA 13, 161-169] and Rodin and Rodin [Rodin, S.N., Rodin, A.S., 2008. On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases. Heredity 100, 341-355], respectively.

Regulation of the Cardiac Muscle Ryanodine Receptor by O2 Tension and S-Nitrosoglutathione†

PubMed Central

Sun, Junhui; Yamaguchi, Naohiro; Xu, Le; Eu, Jerry P.; Stamler, Jonathan S.; Meissner, Gerhard

2009-01-01

The cardiac and skeletal muscle sarcoplasmic reticulum ryanodine receptor Ca2+ release channels contain thiols that are potential targets of endogenously produced reactive oxygen and nitrogen intermediates. Previously, we showed that the skeletal muscle ryanodine receptor (RyR1) has O2-sensitive thiols; only when these thiols are in the reduced state (pO2 ~ 10 mmHg) can physiological concentrations of NO (nanomolar) activate RyR1. Here, we report that cardiac muscle ryanodine receptor (RyR2) activity also depends on pO2, but unlike RyR1, RyR2 was not activated or S-nitrosylated directly by NO. Rather, activation and S-nitrosylation of RyR2 required S-nitrosoglutathione. The effects of peroxynitrite were indiscriminate on RyR1 and RyR2. Our results indicate that both RyR1 and RyR2 are pO2-responsive yet point to different mechanisms by which NO and S-nitrosoglutathione influence cardiac and skeletal muscle sarcoplasmic reticulum Ca2+ release. PMID:19053230

A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

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

Zhang, Xuenong; Wei, Han; Liu, Ziwei

Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed thatmore » RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death.« less

Type-3 ryanodine receptors mediate hypoxia-, but not neurotransmitter-induced calcium release and contraction in pulmonary artery smooth muscle cells.

PubMed

Zheng, Yun-Min; Wang, Qing-Song; Rathore, Rakesh; Zhang, Wan-Hui; Mazurkiewicz, Joseph E; Sorrentino, Vincenzo; Singer, Harold A; Kotlikoff, Michael I; Wang, Yong-Xiao

2005-04-01

In this study we examined the expression of RyR subtypes and the role of RyRs in neurotransmitter- and hypoxia-induced Ca2+ release and contraction in pulmonary artery smooth muscle cells (PASMCs). Under perforated patch clamp conditions, maximal activation of RyRs with caffeine or inositol triphosphate receptors (IP3Rs) with noradrenaline induced equivalent increases in [Ca2+]i and Ca2+-activated Cl- currents in freshly isolated rat PASMCs. Following maximal IP3-induced Ca2+ release, neither caffeine nor chloro-m-cresol induced a response, whereas prior application of caffeine or chloro-m-cresol blocked IP3-induced Ca2+ release. In cultured human PASMCs, which lack functional expression of RyRs, caffeine failed to affect ATP-induced increases in [Ca2+]i in the presence and absence of extracellular Ca2+. The RyR antagonists ruthenium red, ryanodine, tetracaine, and dantrolene greatly inhibited submaximal noradrenaline- and hypoxia-induced Ca2+ release and contraction in freshly isolated rat PASMCs, but did not affect ATP-induced Ca2+ release in cultured human PASMCs. Real-time quantitative RT-PCR and immunofluorescence staining indicated similar expression of all three RyR subtypes (RyR1, RyR2, and RyR3) in freshly isolated rat PASMCs. In freshly isolated PASMCs from RyR3 knockout (RyR3-/-) mice, hypoxia-induced, but not submaximal noradrenaline-induced, Ca2+ release and contraction were significantly reduced. Ruthenium red and tetracaine can further inhibit hypoxic increase in [Ca2+]i in RyR3-/- mouse PASMCs. Collectively, our data suggest that (a) RyRs play an important role in submaximal noradrenaline- and hypoxia-induced Ca2+ release and contraction; (b) all three subtype RyRs are expressed; and (c) RyR3 gene knockout significantly inhibits hypoxia-, but not submaximal noradrenaline-induced Ca2+ and contractile responses in PASMCs.

Near-infrared variability study of the central 2.3 arcmin × 2.3 arcmin of the Galactic Centre - I. Catalogue of variable sources

NASA Astrophysics Data System (ADS)

Dong, Hui; Schödel, Rainer; Williams, Benjamin F.; Nogueras-Lara, Francisco; Gallego-Cano, Eulalia; Gallego-Calvente, Teresa; Wang, Q. Daniel; Morris, Mark R.; Do, Tuan; Ghez, Andrea

2017-09-01

We used 4-yr baseline Hubble Space Telescope/Wide Field Camera 3 IR observations of the Galactic Centre in the F153M band (1.53 μm) to identify variable stars in the central ∼2.3 arcmin × 2.3 arcmin field. We classified 3845 long-term (periods from months to years) and 76 short-term (periods of a few days or less) variables among a total sample of 33 070 stars. For 36 of the latter ones, we also derived their periods (<3 d). Our catalogue not only confirms bright long period variables and massive eclipsing binaries identified in previous works but also contains many newly recognized dim variable stars. For example, we found δ Scuti and RR Lyrae stars towards the Galactic Centre for the first time, as well as one BL Her star (period < 1.3 d). We cross-correlated our catalogue with previous spectroscopic studies and found that 319 variables have well-defined stellar types, such as Wolf-Rayet, OB main sequence, supergiants and asymptotic giant branch stars. We used colours and magnitudes to infer the probable variable types for those stars without accurately measured periods or spectroscopic information. We conclude that the majority of unclassified variables could potentially be eclipsing/ellipsoidal binaries and Type II Cepheids. Our source catalogue will be valuable for future studies aimed at constraining the distance, star formation history and massive binary fraction of the Milky Way nuclear star cluster.

Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

NASA Technical Reports Server (NTRS)

Clancy, J. S.; Takeshima, H.; Hamilton, S. L.; Reid, M. B.

1999-01-01

Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

FUSE Observations of the Active Interacting Binary RY Persei

NASA Astrophysics Data System (ADS)

Peters, G. J.; Polidan, R. S.

2003-12-01

RY Per (HD 17034, B4 V + F7 II-III, P=6.86 d) is a massive interacting binary (6.25 M⊙ + 1.60 M⊙, Olson & Plavec 1997, AJ, 113, 425) that displays a variable weak accretion disk that emits in Hα (Barai, et al., preprint). FUSE observations of this system, carried through in 2002 October at phases 0.20, 0.57, and 0.97 and during its total eclipse on 2002 December 8 are presented. The totality data were binned into two phase intervals: 0.0056-0.9976 (after second contact) and 0.0052-0.0089 (just before third contact). Both eclipse observations reveal broad, prominent emission lines of N III (UV1, λ λ 990-992 Å), O VI (UV1, λ λ 1032,1038 Å), N II (UV1, λ λ 1084-1086 Å), Si III (UV5, λ λ 1108,1109,1113 Å), Si IV(UV3, λ λ 1122,1138 Å), and Fe III (UV1, λ λ 1122-32 Å). Emission from C III (UV4, λ 1176 Å) seen during totality in FUSE observations of the Algol binaries V356 Sgr and TT Hya is conspicuously absent. C III (UV1, λ 977 Å) is also absent. This observation combined with the strong presence of N II, III emission suggests that material processed through the CNO cycle in the mass loser is now being transferred to the B star. The FUSE data imply that the emitting plasma is hot ( ˜100,000-300,000 K) and located above/below the orbital plane. The source of this apparent bipolar flow (also seen in V356 Sgr and TT Hya) may be the splash region detected near phase 0.5 in IUE observations of the N V resonance line, but absorption features from this region were not seen in the non-eclipse FUSE observations. A model for the circumstellar material in this system will be presented and the FUSE observations will be compared with those of V356 Sgr and TT Hya. GJP is grateful for support from NASA Grant NAG5-12253.

Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice.

PubMed

Huang, Fannie; Shan, Jian; Reiken, Steven; Wehrens, Xander H T; Marks, Andrew R

2006-02-28

The ryanodine receptor (RyR)/calcium-release channel on the sarcoplasmic reticulum mediates intracellular calcium release required for striated muscle contraction. RyR2, the predominant isoform in cardiac myocytes, comprises a macromolecular complex that includes calstabin2 (FKBP12.6). Calstabin2, an 11.8-kDa cis-trans peptidyl-prolyl isomerase (apparent molecular mass 12.6 kDa), stabilizes the closed state of the RyR2 channel, but the mechanism by which it achieves this regulation is not fully understood. Protein kinase A (PKA) phosphorylation of RyR2 decreases the affinity of calstabin2 for the RyR2 channel complex. In the present study we identified key aspartic acid residues on calstabin2 that are involved in binding to RyR2 and likely play a role in PKA phosphorylation-induced dissociation of calstabin2 from RyR2. We show that a mutant calstabin2 in which a key negatively charged residue (Asp-37) has been neutralized binds to a mutant RyR2 channel that mimics constitutively PKA-phosphorylated RyR2 (RyR2-S2808D). Furthermore, using wild-type and genetically altered murine models of heart failure induced by myocardial infarction, we show that manipulating the stoichiometry between calstabin2 and RyR2 can restore normal cardiac function in vivo.

The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes.

PubMed

Bovo, Elisa; Huke, Sabine; Blatter, Lothar A; Zima, Aleksey V

2017-03-01

Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca 2+ release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca 2+ ] and intra-SR [Ca 2+ ] SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies. cAMP (10μM) increased Ca 2+ spark frequency approximately two-fold. This effect was associated with an increase in SR Ca 2+ load from 0.84 to 1.24mM. PKA inhibitory peptide (PKI; 10μM) abolished the cAMP-dependent increase of SR Ca 2+ load and spark frequency. When SERCA was completely blocked by thapsigargin, cAMP did not affect RyR2-mediated Ca 2+ leak. The lack of a cAMP effect on RyR2 function can be explained by almost maximal phosphorylation of RyR2 at serine-2809 after sarcolemma permeabilization. This high RyR2 phosphorylation level is likely the consequence of a balance shift between protein kinase and phosphatase activity after permeabilization. When RyR2 phosphorylation at serine-2809 was reduced to its "basal" level (i.e. RyR2 phosphorylation level in intact myocytes) using kinase inhibitor staurosporine, SR Ca 2+ leak was significantly reduced. Surprisingly, further dephosphorylation of RyR2 with protein phosphatase 1 (PP1) markedly increased SR Ca 2+ leak. At the same time, phosphorylation of RyR2 at serine 2031 did not significantly change under identical experimental conditions. These results suggest that RyR2 phosphorylation by PKA has a complex effect on SR Ca 2+ leak in ventricular myocytes. At an intermediate level of RyR2 phosphorylation SR Ca 2+ leak is minimal. However, complete dephosphorylation and maximal phosphorylation of RyR2 increases SR Ca 2+ leak. Copyright © 2017 Elsevier Ltd. All rights reserved.

The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells.

PubMed

Wang, Shi Qiang; Stern, Michael D; Ríos, Eduardo; Cheng, Heping

2004-03-16

Intracellular Ca(2+) release in many types of cells is mediated by ryanodine receptor Ca(2+) release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca(2+) release events, Ca(2+) sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca(2+) release flux. Analysis of the quantal property of Ca(2+) sparks provided a view of unitary Ca(2+) current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca(2+)-induced Ca(2+) release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca(2+) signaling.

Convection and Overshoot in Models of Doradus and Scuti Stars

DOE PAGES

Lovekin, Catherine C.; Guzik, Joyce Ann

2017-10-27

We investigate the pulsation properties of stellar models that are representative of δ Scuti and γ Doradus variables. Here we have calculated a grid of stellar models from 1.2 to 2.2 M ⊙, including the effects of both rotation and convective overshoot using MESA, and we investigate the pulsation properties of these models using GYRE. We discuss the observable patterns in the frequency spacing for p modes and the period spacings for g modes. Using the observable patterns in the g mode period spacings, it may be possible to observationally constrain the convective overshoot and rotation of a model. Wemore » also calculate the pulsation constant (Q) for all models in our grid and investigate the variation with convective overshoot and rotation. The variation in the Q values of the radial modes can be used to place constraints on the convective overshoot and rotation of stars in this region. Finally, as a test case, we apply this method to a sample of 22 High-Amplitude δ Scuti stars (HADS) and provide estimates for the convective overshoot of the sample.« less

The δ Scuti pulsations of β Pictoris as observed by ASTEP from Antarctica

NASA Astrophysics Data System (ADS)

Mékarnia, D.; Chapellier, E.; Guillot, T.; Abe, L.; Agabi, A.; De Pra, Y.; Schmider, F.-X.; Zwintz, K.; Stevenson, K. B.; Wang, J. J.; Lagrange, A.-M.; Bigot, L.; Crouzet, N.; Fanteï-Caujolle, Y.; Christille, J.-M.; Kalas, P.

2017-12-01

Aims: The Antarctica Search for Transiting Extrasolar Planets (ASTEP), an automatized 400 mm telescope located at Concordia station in Antarctica, monitored β Pictoris continuously to detect any variability linked to the transit of the Hill sphere of its planet β Pictoris b. The long observation sequence, from March to September 2017, combined with the quality and high level duty cycle of our data, enables us to detect and analyse the δ Scuti pulsations of the star. Methods: Time series photometric data were obtained using aperture photometry by telescope defocussing. The 66 418 data points were analysed using the software package Period04. We only selected frequencies with amplitudes that exceed four times the local noise level in the amplitude spectrum. Results: We detect 31 δ Scuti pulsation frequencies, 28 of which are new detections. All the frequencies detected are in the interval 34.76-75.68 d-1. We also find that β Pictoris exhibits at least one pulsation mode that varies in amplitude over our monitoring duration of seven months.

Convection and Overshoot in Models of Doradus and Scuti Stars

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

Lovekin, Catherine C.; Guzik, Joyce Ann

We investigate the pulsation properties of stellar models that are representative of δ Scuti and γ Doradus variables. Here we have calculated a grid of stellar models from 1.2 to 2.2 M ⊙, including the effects of both rotation and convective overshoot using MESA, and we investigate the pulsation properties of these models using GYRE. We discuss the observable patterns in the frequency spacing for p modes and the period spacings for g modes. Using the observable patterns in the g mode period spacings, it may be possible to observationally constrain the convective overshoot and rotation of a model. Wemore » also calculate the pulsation constant (Q) for all models in our grid and investigate the variation with convective overshoot and rotation. The variation in the Q values of the radial modes can be used to place constraints on the convective overshoot and rotation of stars in this region. Finally, as a test case, we apply this method to a sample of 22 High-Amplitude δ Scuti stars (HADS) and provide estimates for the convective overshoot of the sample.« less

Turbulent Convection and Pulsation Stability of Stars

NASA Astrophysics Data System (ADS)

Xiong, Da-run

2017-10-01

The controversies about the excitation mechanism for low-temperature variables are reviewed: (1) Most people believe that γ Doradus variables are excited by the so-called convective blocking mechanism. Our researches show that the excitation of γ Doradus has no substantial difference from that of δ Scuti. They are two subgroups of a broader type of δ Stuti-γ Doradus stars: δ Scuti is the p-mode subgroup, while γ Doradus is the g-mode subgroup. (2) Most people believe that the solar and stellar solar-like oscillations are damped by convection, and they are driven by the so-called turbulent random excitation mechanism. Our researches show that convection is not solely a damping mechanism for stellar oscillations, otherwise it is unable to explain the Mira and Mira-like variables. By using our non-local and time-dependent theory of convection, we can reproduce not only the pulsationally unstable strip of δ Scuti and γ Doradus variables, but also the solar-like oscillation features of low-luminosity red giants and the Mira-like oscillation features of high-luminosity red giants.

Convection and Overshoot in Models of γ Doradus and δ Scuti Stars

NASA Astrophysics Data System (ADS)

Lovekin, C. C.; Guzik, J. A.

2017-11-01

We investigate the pulsation properties of stellar models that are representative of δ Scuti and γ Doradus variables. We have calculated a grid of stellar models from 1.2 to 2.2 M ⊙, including the effects of both rotation and convective overshoot using MESA, and we investigate the pulsation properties of these models using GYRE. We discuss the observable patterns in the frequency spacing for p modes and the period spacings for g modes. Using the observable patterns in the g mode period spacings, it may be possible to observationally constrain the convective overshoot and rotation of a model. We also calculate the pulsation constant (Q) for all models in our grid and investigate the variation with convective overshoot and rotation. The variation in the Q values of the radial modes can be used to place constraints on the convective overshoot and rotation of stars in this region. As a test case, we apply this method to a sample of 22 High-Amplitude δ Scuti stars (HADS) and provide estimates for the convective overshoot of the sample.

Searching for new white dwarf pulsators for TESS observations at Konkoly Observatory

NASA Astrophysics Data System (ADS)

Bognár, Zs; Kalup, Cs; Sódor, Á.; Charpinet, S.; Hermes, J. J.

2018-07-01

We present the results of our survey searching for new white dwarf pulsators for observations by the TESS space telescope. We collected photometric time-series data on 14 white dwarf variable candidates at Konkoly Observatory, and found two new bright ZZ Ceti stars, namely EGGR 120 and WD 1310+583. We performed a Fourier analysis of the datasets. In the case of EGGR 120, which was observed on one night only, we found one significant frequency at 1332μHz with 2.3 mmag amplitude. We successfully observed WD 1310+583 on eight nights, and determined 17 significant frequencies in the whole dataset. Seven of them seem to be independent pulsation modes between 634 and 2740μHz, and we performed preliminary asteroseismic investigations of the star utilizing six of these periods. We also identified three new light variables on the fields of white dwarf candidates: an eclipsing binary, a candidate delta Scuti/beta Cephei and a candidate W UMa-type star.

PHOTOMETRY OF VARIABLE STARS FROM DOME A, ANTARCTICA

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

Wang Lingzhi; Macri, Lucas M.; Krisciunas, Kevin

Dome A on the Antarctic plateau is likely one of the best observing sites on Earth thanks to the excellent atmospheric conditions present at the site during the long polar winter night. We present high-cadence time-series aperture photometry of 10,000 stars with i < 14.5 mag located in a 23 deg{sup 2} region centered on the south celestial pole. The photometry was obtained with one of the CSTAR telescopes during 128 days of the 2008 Antarctic winter. We used this photometric data set to derive site statistics for Dome A and to search for variable stars. Thanks to the nearlymore » uninterrupted synoptic coverage, we found six times as many variables as previous surveys with similar magnitude limits. We detected 157 variable stars, of which 55% were unclassified, 27% were likely binaries, and 17% were likely pulsating stars. The latter category includes {delta} Scuti, {gamma} Doradus, and RR Lyrae variables. One variable may be a transiting exoplanet.« less

Differential expression of ryanodine receptor isoforms after spinal cord injury.

PubMed

Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

2017-11-01

Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Catecholamime Interactions with the Cardiac Ryanodine Receptor

NASA Astrophysics Data System (ADS)

Klipp, Robert Carl

The cardiac ryanodine receptor (RyR2) is a Ca2+ ion channel found in the sarcoplasmic reticulum (SR), an intracellular membranous Ca2+ storage system. It is well known that a destabilization of RyR2 can lead to a Ca2+ flux out of the SR, which results in an overload of intracellular Ca2+; this can also lead to arrhythmias and heart failure. The catecholamines play a large role in the regulation of RyR2; stimulation of the beta-adrenergic receptor on the cell membrane can lead to a hyperphosphorylation of RyR2, making it more leaky to Ca2+. We have previously shown that strong electron donors will inhibit RyR2. It is hypothesized that the catecholamines, sharing a similar structure with other proven inhibitors of RyR2, will also inhibit RyR2. Here we confirm this hypothesis and show for the first time that the catecholamines, isoproterenol and epinephrine, act as strong electron donors and inhibit RyR2 activity at the single channel level. This data suggests that the catecholamines can influence RyR2 activity at two levels. This offers promising insight into the potential development of a new class of drugs to treat heart failure and arrhythmia; ones that can both prevent the hyperphosphorylation of RyR2 by blocking the beta-adrenergic receptor, but can also directly inhibit the release of Ca2+ from RyR2.

Bioinformatic mapping and production of recombinant N-terminal domains of human cardiac ryanodine receptor 2

PubMed Central

Bauerová-Hlinková, Vladena; Hostinová, Eva; Gašperík, Juraj; Beck, Konrad; Borko, Ľubomír; Lai, F. Anthony; Zahradníková, Alexandra; Ševčík, Jozef

2010-01-01

We report the domain analysis of the N-terminal region (residues 1–759) of the human cardiac ryanodine receptor (RyR2) that encompasses one of the discrete RyR2 mutation clusters associated with catecholaminergic polymorphic ventricular tachycardia (CPVT1) and arrhythmogenic right ventricular dysplasia (ARVD2). Our strategy utilizes a bioinformatics approach complemented by protein expression, solubility analysis and limited proteolytic digestion. Based on the bioinformatics analysis, we designed a series of specific RyR2 N-terminal fragments for cloning and overexpression in Escherichia coli. High yields of soluble proteins were achieved for fragments RyR21–606·His6, RyR2391–606·His6, RyR2409–606·His6, Trx·RyR2384–606·His6, Trx·RyR2391-606·His6 and Trx·RyR2409–606·His6. The folding of RyR21–606·His6 was analyzed by circular dichroism spectroscopy resulting in α-helix and β-sheet content of ∼23% and ∼29%, respectively, at temperatures up to 35 °C, which is in agreement with sequence based secondary structure predictions. Tryptic digestion of the largest recombinant protein, RyR21–606·His6, resulted in the appearance of two specific subfragments of ∼40 and 25 kDa. The 25 kDa fragment exhibited greater stability. Hybridization with anti-His6·Tag antibody indicated that RyR21–606·His6 is cleaved from the N-terminus and amino acid sequencing of the proteolytic fragments revealed that digestion occurred after residues 259 and 384, respectively. PMID:20045464

Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes

PubMed Central

Petrovič, Pavol; Valent, Ivan; Cocherová, Elena; Pavelková, Jana

2015-01-01

The role of cardiac ryanodine receptor (RyR) gating in the initiation and propagation of calcium waves was investigated using a mathematical model comprising a stochastic description of RyR gating and a deterministic description of calcium diffusion and sequestration. We used a one-dimensional array of equidistantly spaced RyR clusters, representing the confocal scanning line, to simulate the formation of calcium sparks. Our model provided an excellent description of the calcium dependence of the frequency of diastolic calcium sparks and of the increased tendency for the production of calcium waves after a decrease in cytosolic calcium buffering. We developed a hypothesis relating changes in the propensity to form calcium waves to changes of RyR gating and tested it by simulation. With a realistic RyR gating model, increased ability of RyR to be activated by Ca2+ strongly increased the propensity for generation of calcium waves at low (0.05–0.1-µM) calcium concentrations but only slightly at high (0.2–0.4-µM) calcium concentrations. Changes in RyR gating altered calcium wave formation by changing the calcium sensitivity of spontaneous calcium spark activation and/or the average number of open RyRs in spontaneous calcium sparks. Gating changes that did not affect RyR activation by Ca2+ had only a weak effect on the propensity to form calcium waves, even if they strongly increased calcium spark frequency. Calcium waves induced by modulating the properties of the RyR activation site could be suppressed by inhibiting the spontaneous opening of the RyR. These data can explain the increased tendency for production of calcium waves under conditions when RyR gating is altered in cardiac diseases. PMID:26009544

Chemical composition of δ Scuti stars: 1. AO CVn, CP Boo, KW Aur

NASA Astrophysics Data System (ADS)

Galeev, A. I.; Ivanova, D. V.; Shimansky, V. V.; Bikmaev, I. F.

2012-11-01

We used high-resolution echelle spectra acquired with the 1.5-m Russian-Turkish Telescope to determine the fundamental atmospheric parameters and abundances of 30 chemical elements for three δ Scuti stars: AOCVn, CP Boo, and KWAur. The chemical compositions we find for these stars are similar to those for Am-star atmospheres, though some anomalies of up to 0.6-0.7 dex are observed for light and heavy elements. We consider the effect of the adopted stellar parameters (effective temperature, log g, microturbulent velocity) and the amplitude of pulsational variations on the derived elemental abundances.

Characterization of Ryanodine Receptor Type 1 Single Channel Activity Using “On-Nucleus” Patch Clamp

PubMed Central

Wagner, Larry E.; Groom, Linda A.; Dirksen, Robert T.; Yule, David I.

2014-01-01

In this study, we provide the first description of the biophysical and pharmacological properties of ryanodine receptor type 1 (RyR1) expressed in a native membrane using the on-nucleus configuration of the patch clamp technique. A stable cell line expressing rabbit RyR1 was established (HEK-RyR1) using the FLP-in 293 cell system. In contrast to untransfected cells, RyR1 expression was readily demonstrated by immunoblotting and immunocytochemistry in HEK-RyR1 cells. In addition, the RyR1 agonists 4-CMC and caffeine activated Ca2+ release that was inhibited by high concentrations of ryanodine. On nucleus patch clamp was performed in nuclei prepared from HEK-RyR1 cells. Raising the [Ca2+] in the patch pipette resulted in the appearance of a large conductance cation channel with well resolved kinetics and the absence of prominent subconductance states. Current versus voltage relationships were ohmic and revealed a chord conductance of ~750 pS or 450 pS in symmetrical 250 mM KCl or CsCl, respectively. The channel activity was markedly enhanced by caffeine and exposure to ryanodine resulted in the appearance of a subconductance state with a conductance ~40 % of the full channel opening with a Po near unity. In total, these properties are entirely consistent with RyR1 channel activity. Exposure of RyR1 channels to cyclic ADP ribose (cADPr), nicotinic acid adenine dinucleotide phosphate (NAADP) or dantrolene did not alter the single channel activity stimulated by Ca2+, and thus, it is unlikely these molecules directly modulate RyR1 channel activity. In summary, we describe an experimental platform to monitor the single channel properties of RyR channels. We envision that this system will be influential in characterizing disease-associated RyR mutations and the molecular determinants of RyR channel modulation. PMID:24972488

Establishment of a rat hepatoma-derived cell line proliferating in D-phenylalanine medium and expressing D-amino-acid oxidase.

PubMed

Yoda, N; Konno, R; Nagashima, S

2001-01-01

A cell line (R-Y121B.DF) has been established from a cell line (R-Y121B) derived from a rat hepatoma line (H4-II-E). The R-Y121B.DF cells have been continuously cultured in a serum-free modified Eagle's minimum essential medium in which L-phenylalanine was replaced by D-phenylalanine. They had D-amino-acid oxidase (DAO) activity which is essential for the growth in the medium containing D-amino acids. The enzyme activity of the R-Y121B.DF cells was approximately one-fourth of that of the rat liver. Northern hybridization using a DAO cDNA probe detected a hybridizing signal in the R-Y121B.DF cells and the rat liver but not in the parental R-Y121B and H4-II-E cells. Reverse transcription-polymerase chain reaction using DAO-specific primers amplified a DNA fragment of the expected size in the R-Y121B.DF cells but not in the R-Y121B and H4-II-E cells. This fragment was confirmed to be DAO cDNA by nucleotide sequencing. Western blotting showed that DAO protein was present in the R-Y121B.DF cells and the rat liver but not in the R-Y121B and H4-II-E cells. Southern hybridization showed that the DAO gene structure was not different among the R-Y121B.DF cells, R-Y121B cells, H4-II-E cells, and the rat liver. These results indicate that the R-Y121B.DF is a unique cell line which proliferates in the medium containing D-phenylalanine and explicitly expresses DAO. This line is useful for the study of DAO in vitro.

DISCOVERY OF 14 NEW SLOWLY PULSATING B STARS IN THE OPEN CLUSTER NGC 7654

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

Luo, Y. P.; Han, Z. W.; Zhang, X. B.

2012-02-10

We carried out time-series BV CCD photometric observations of the open cluster NGC 7654 (Messier 52) to search for variable stars. Eighteen slowly pulsating B (SPB) stars have been detected, among which 14 candidates are newly discovered, three known ones are confirmed, and a previously found {delta} Scuti star is also identified as an SPB candidate. Twelve SPBs are probable cluster members based on membership analysis. This makes NGC 7654 the richest galactic open cluster in terms of SPB star content. It is also a new discovery that NGC 7654 hosts three {gamma} Dor star candidates. We found that allmore » these stars (18 SPB and 3 {gamma} Dor stars) have periods longer than their corresponding fundamental radial mode. With such a big sample of g-mode pulsators in a single cluster, it is clear that multi-mode pulsation is more common in the upper part of the main sequence than in the lower part. All the stars span a narrow strip on the period-luminosity plane, which also includes the {gamma} Dor stars at the low-luminosity extension. This result implies that there may be a single period-luminosity relation applicable to all g-mode main-sequence pulsators. As a by-product, three EA-type eclipsing binaries and an EW-type eclipsing binary are also discovered.« less

Structural mapping of divergent regions in the type 1 ryanodine receptor using fluorescence resonance energy transfer

PubMed Central

Mahalingam, Mohana; Girgenrath, Tanya; Svensson, Bengt; Thomas, David D.; Cornea, Razvan L.; Fessenden, James D.

2014-01-01

Summary Ryanodine receptors (RyR) release Ca2+ to initiate striated muscle contraction. Three highly divergent regions in the RyR protein sequence (DR1, DR2, DR3) are proposed to confer isoform-specific functional properties to the RyRs. We used cell-based fluorescence resonance energy transfer (FRET) measurements to localize these DRs to the cryo-electron microscopic (EM) map of the skeletal muscle RyR isoform (RyR1). FRET donors were targeted to RyR1 using five different FKBP12.6 variants labeled with Alexa Fluor 488. FRET was then measured to Cy3NTA or Cy5NTA, FRET acceptors targeted to decahistidine tags introduced within the DRs. DR2 and DR3 were localized to separate positions within the “clamp” region of the RyR1 cryo-EM map, which is presumed to interface with Cav1.1. DR1 was localized to the “handle” region, near the regulatory calmodulin binding site on the RyR. These localizations provide new insights into the roles of DRs in RyR allosteric regulation during excitation-contraction coupling. PMID:25132084

Unexpected series of regular frequency spacing of δ Scuti stars in the non-asymptotic regime - I. The methodology

DOE PAGES

Paparo, M.; Benko, J. M.; Hareter, M.; ...

2016-05-11

In this study, a sequence search method was developed to search the regular frequency spacing in δ Scuti stars through visual inspection and an algorithmic search. We searched for sequences of quasi-equally spaced frequencies, containing at least four members per sequence, in 90 δ Scuti stars observed by CoRoT. We found an unexpectedly large number of independent series of regular frequency spacing in 77 δ Scuti stars (from one to eight sequences) in the non-asymptotic regime. We introduce the sequence search method presenting the sequences and echelle diagram of CoRoT 102675756 and the structure of the algorithmic search. Four sequencesmore » (echelle ridges) were found in the 5–21 d –1 region where the pairs of the sequences are shifted (between 0.5 and 0.59 d –1) by twice the value of the estimated rotational splitting frequency (0.269 d –1). The general conclusions for the whole sample are also presented in this paper. The statistics of the spacings derived by the sequence search method, by FT (Fourier transform of the frequencies), and the statistics of the shifts are also compared. In many stars more than one almost equally valid spacing appeared. The model frequencies of FG Vir and their rotationally split components were used to formulate the possible explanation that one spacing is the large separation while the other is the sum of the large separation and the rotational frequency. In CoRoT 102675756, the two spacings (2.249 and 1.977 d –1) are in better agreement with the sum of a possible 1.710 d –1 large separation and two or one times, respectively, the value of the rotational frequency.« less

Understanding the dynamical structure of pulsating stars: The Baade-Wesselink projection factor of the δ Scuti stars AI Velorum and β Cassiopeiae

NASA Astrophysics Data System (ADS)

Guiglion, G.; Nardetto, N.; Mathias, P.; Domiciano de Souza, A.; Poretti, E.; Rainer, M.; Fokin, A.; Mourard, D.; Gieren, W.

2013-02-01

Aims: The Baade-Wesselink method of distance determination is based on the oscillations of pulsating stars. The key parameter of this method is the projection factor used to convert the radial velocity into the pulsation velocity. Our analysis was aimed at deriving for the first time the projection factor of δ Scuti stars, using high-resolution spectra of the high-amplitude pulsator AI Vel and of the fast rotator β Cas. Methods: The geometric component of the projection factor (i.e. p0) was calculated using a limb-darkening model of the intensity distribution for AI Vel, and a fast-rotator model for β Cas. Then, using SOPHIE/OHP data for β Cas and HARPS/ESO data for AI Vel, we compared the radial velocity curves of several spectral lines forming at different levels in the atmosphere and derived the velocity gradient associated to the spectral-line-forming regions in the atmosphere of the star. This velocity gradient was used to derive a dynamical projection factor p. Results: We find a flat velocity gradient for both stars and finally p = p0 = 1.44 for AI Vel and p = p0 = 1.41 for β Cas. By comparing Cepheids and δ Scuti stars, these results bring valuable insights into the dynamical structure of pulsating star atmospheres. They suggest that the period-projection factor relation derived for Cepheids is also applicable to δ Scuti stars pulsating in a dominant radial mode. This work uses observations made with the HARPS instrument at the 3.6 m telescope (La Silla, Chile) in the framework of the LP185.D-0056 and with the SOPHIE instrument at OHP (France).

Unexpected series of regular frequency spacing of δ Scuti stars in the non-asymptotic regime - I. The methodology

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

Paparo, M.; Benko, J. M.; Hareter, M.

In this study, a sequence search method was developed to search the regular frequency spacing in δ Scuti stars through visual inspection and an algorithmic search. We searched for sequences of quasi-equally spaced frequencies, containing at least four members per sequence, in 90 δ Scuti stars observed by CoRoT. We found an unexpectedly large number of independent series of regular frequency spacing in 77 δ Scuti stars (from one to eight sequences) in the non-asymptotic regime. We introduce the sequence search method presenting the sequences and echelle diagram of CoRoT 102675756 and the structure of the algorithmic search. Four sequencesmore » (echelle ridges) were found in the 5–21 d –1 region where the pairs of the sequences are shifted (between 0.5 and 0.59 d –1) by twice the value of the estimated rotational splitting frequency (0.269 d –1). The general conclusions for the whole sample are also presented in this paper. The statistics of the spacings derived by the sequence search method, by FT (Fourier transform of the frequencies), and the statistics of the shifts are also compared. In many stars more than one almost equally valid spacing appeared. The model frequencies of FG Vir and their rotationally split components were used to formulate the possible explanation that one spacing is the large separation while the other is the sum of the large separation and the rotational frequency. In CoRoT 102675756, the two spacings (2.249 and 1.977 d –1) are in better agreement with the sum of a possible 1.710 d –1 large separation and two or one times, respectively, the value of the rotational frequency.« less

KIC 6048106: an Algol-type eclipsing system with long-term magnetic activity and hybrid pulsations - I. Binary modelling

NASA Astrophysics Data System (ADS)

Samadi Ghadim, A.; Lampens, P.; Jassur, M.

2018-03-01

The A-F-type stars and pulsators (δ Scuti-γ Dor) are in a critical regime where they experience a transition from radiative to convective transport of energy in their envelopes. Such stars can pulsate in both gravity and acoustic modes. Hence, the knowledge of their fundamental parameters along with their observed pulsation characteristics can help in improving the stellar models. When residing in a binary system, these pulsators provide more accurate and less model-dependent stellar parameters than in the case of their single counterparts. We present a light-curve model for the eclipsing system KIC 6048106 based on the Kepler photometry and the code PHOEBE. We aim to obtain accurate physical parameters and tough constraints for the stellar modelling of this intermediate-mass hybrid pulsator. We performed a separate modelling of three light-curve segments which show a distinct behaviour due to a difference in activity. We also analysed the Kepler Eclipse Time Variations (ETVs). KIC 6048106 is an Algol-type binary with F5-K5 components, a near-circular orbit and a 1.56-d period undergoing variations of the order of Δ P/P˜eq 3.60× 10^{-7} in 287 ± 7 d. The primary component is a main-sequence star with M1 = 1.55 ± 0.11 M⊙, R1 = 1.57 ± 0.12 R⊙. The secondary is a much cooler subgiant with M2 = 0.33 ± 0.07 M⊙, R2 = 1.77 ± 0.16 R⊙. Many small near-polar spots are active on its surface. The second quadrature phase shows a brightness modulation on a time-scale 290 ± 7 d, in good agreement with the ETV modulation. This study reveals a stable binary configuration along with clear evidence of a long-term activity of the secondary star.

[RyR-bound FKBP12.6 and the modulation].

PubMed

Yano, M; Matsuzaki, M

2001-06-01

In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+) -ATPase is believed to be a major determinant. Recently, a novel mechanism of cardiac dysfunction in heart failure has been reported on the basis of the following findings:1) PKA hyperphosphorylation of RyR causes a dissociation of FKBP12.6 from RyR, resulting in the abnormal single-channel properties (increased Ca(2+) sensitivity for activation and elevated channel activity associated with destabilization of RyR (Marx et al, Cell 101:365, 2000), 2) a prominent abnormal Ca(2+) leak occurs through RyR, following a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR (Yano M et al, Circulation 102:2131, 2000). This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Functionally heterogenous ryanodine receptors in avian cerebellum.

PubMed

Sierralta, J; Fill, M; Suárez-Isla, B A

1996-07-19

The functional heterogeneity of the ryanodine receptor (RyR) channels in avian cerebellum was defined. Heavy endoplasmic reticulum microsomes had significant levels of ryanodine and inositol 1,4,5-trisphosphate binding. Scatchard analysis and kinetic studies indicated the existence of at least two distinct ryanodine binding sites. Ryanodine binding was calcium-dependent but was not significantly enhanced by caffeine. Incorporation of microsomes into planar lipid bilayers revealed ion channels with pharmacological features (calcium, magnesium, ATP, and caffeine sensitivity) similar to the RyR channels found in mammalian striated muscle. Despite a wide range of unitary conductances (220-500 picosiemens, symmetrical cesium methanesulfonate), ryanodine locked both channels into a characteristic slow gating subconductance state, positively identifying them as RyR channels. Two populations of avian RyR channels were functionally distinguished by single channel calcium sensitivity. One population was defined by a bell-shaped calcium sensitivity analogous to the skeletal muscle RyR isoform (type I). The calcium sensitivity of the second RyR population was sigmoidal and analogous to the cardiac muscle RyR isoform (type II). These data show that there are at least two functionally distinct RyR channel populations in avian cerebellum. This leads to the possibility that these functionally distinct RyR channels are involved in different intracellular calcium signaling pathways.

Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the balance right.

PubMed

Currie, Susan

2009-06-01

Phosphorylation of the cardiac ryanodine receptor (RyR2) is a key mechanism regulating sarcoplasmic reticulum (SR) Ca2+ release. Differences in opinion have arisen over the importance assigned to specific phosphorylation sites on RyR2, over the kinase (s) suggested to directly phosphorylate RyR2 and surrounding the possibility that altered phosphorylation of RyR2 is associated with contractile dysfunction observed in heart failure. Ca2+/calmodulin dependent protein kinase II (CaMKII) can phosphorylate RyR2 and modulate its activity. This phosphorylation positively modulates cardiac inotropic function but in extreme situations such as heart failure, elevated CaMKII activity can adversely increase Ca2+ release from the SR and lead to arrhythmogenesis. Although other kinases can phosphorylate RyR2, most notably cAMP-dependent protein kinase (PKA), evidence for a key role of CaMKII in mediating RyR2-dependent Ca2+ release is emerging. Future challenges include (i) fully identifying mechanisms of CaMKII interaction with the RyR2 complex and (ii) given the ubiquitous expression of CaMKII, developing selective strategies to modulate RyR2-targeted CaMKII activity and allow improved understanding of its role in normal and diseased heart.

Molecular characterization and expression profiling of ryanodine receptor gene in the pink stem borer, Sesamia inferens (Walker).

PubMed

Wu, Shun-Fan; Zhao, Dan-Dan; Huang, Jing-Mei; Zhao, Si-Qi; Zhou, Li-Qi; Gao, Cong-Fen

2018-04-01

The susceptibilities of three field populations of pink stem borer (PSB), Sesamia inferens (walker) to diamide insecticides, chlorantraniliprole and flubendiamide, were evaluated in this study. The results showed that these PSB field populations were still sensitive to the two diamide insecticides after many years of exposure. To further understand PSB and diamide insecticide, the full-length ryanodine receptor (RyR) cDNA (named as SiRyR), the molecular target of diamide insecticides was cloned from PSB and characterized. The SiRyR gene contains an open reading frame of 15,420 nucleotides, encoding 5140 amino acid residues, which shares 77% to 98% sequence identity with RyR homologous of other insects. All hallmarks of RyR proteins are conserved in the SiRyR protein, including the conserved C-terminal domain with the consensus calcium-biding EF-hands (calcium-binding motif), the six transmembrane domains, as well as mannosyltransferase, IP3R and RyR (pfam02815) (MIR) domains. Real-time qPCR analysis revealed that the highest mRNA expression levels of SiRyR were observed in pupa and adults, especially in males. SiRyR was expressed at the highest level in thorax, and the lowest level in wing. The full genetic characterization of SiRyR could provide useful information for future functional expression studies and for discovery of new insecticides with selective insecticidal activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Dependency of Calcium Alternans on Ryanodine Receptor Refractoriness

PubMed Central

Alvarez-Lacalle, Enric; Cantalapiedra, Inma R.; Peñaranda, Angelina; Cinca, Juan; Hove-Madsen, Leif; Echebarria, Blas

2013-01-01

Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive. Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR2 activation and inactivation. Bi-dimensional maps were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping protocol was used to determine whether alternans was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regions of RyR2 gating parameters where SR calcium loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of alternans both mechanisms contribute. At low inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low activation rates it was caused by alternation in the level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identifying domains where SR calcium load or RyR2 refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due to slow recovery from inactivation can be the cause of calcium alternans even when alternation in SR calcium load is present. PMID:23390511

Streptozotocin-induced diabetes increases disulfide bond formation on cardiac ryanodine receptor (RyR2).

PubMed

Bidasee, Keshore R; Nallani, Karuna; Besch, Henry R; Dincer, U Deniz

2003-06-01

In a previous study, we showed that after 6 weeks of streptozotocin-induced diabetes (6D), expression of type 2 ryanodine receptor calcium-release channels (RyR2) did not change significantly in rat hearts. However, the ability of this protein to bind [3H]ryanodine was compromised. Loss in activity therefore resulted from diabetes-induced increases in post-translational modifications on RyR2. In the present study, the effects of diabetes on one type of modification, namely, changes in oxidative state of reactive sulfhydryls was investigated. RyR2 protein from 6D bound 42.3 +/- 7.6 less [3H]ryanodine than RyR2 from controls (6C). The loss in binding was minimized with 2 weeks of insulin treatment initiated after 4 weeks of diabetes (77.8 +/- 5.5% of 6C). Pretreating RyR2 from 6D with 2 mM dithiothreitol in vitro increases [3H]ryanodine binding by 60.8 +/- 5.3%. Dithiothreitol pretreatment of RyR2 from 6C increased [3H]ryanodine binding by 16.8 +/- 4.3%. The reagent pyrocoll interacts with distinct classes of free sulfhydryl groups on 6C RyR2 to induce two major effects. At concentrations < or = 10 microM, it deactivates RyR2 (decreases [3H]ryanodine binding), whereas at higher concentrations it activates them (increases [3H]ryanodine binding). This reagent was unable to activate RyR2 from 6D. Although RyR2 from insulin-treated animals was deactivated by low concentrations of pyrocoll, it was only partially activated at higher concentrations. These data suggest that the dysfunction of RyR2 induced by diabetes may be due in part to formation of disulfide bonds between adjacent sulfhydryl groups and that these changes were attenuated with insulin treatment.

Coupled gating of skeletal muscle ryanodine receptors is modulated by Ca2+, Mg2+, and ATP

PubMed Central

Porta, Maura; Diaz-Sylvester, Paula L.; Neumann, Jake T.; Escobar, Ariel L.; Fleischer, Sidney

2012-01-01

Coupled gating (synchronous openings and closures) of groups of skeletal muscle ryanodine receptors (RyR1), which mimics RyR1-mediated Ca2+ release underlying Ca2+ sparks, was first described by Marx et al. (Marx SO, Ondrias K, Marks AR. Science 281: 818–821, 1998). The nature of the RyR1-RyR1 interactions for coupled gating still needs to be characterized. Consequently, we defined planar lipid bilayer conditions where ∼25% of multichannel reconstitutions contain mixtures of coupled and independently gating RyR1. In ∼10% of the cases, all RyRs (2–10 channels; most frequently 3–4) gated in coupled fashion, allowing for quantification. Our results indicated that coupling required cytosolic solutions containing ATP/Mg2+ and high (50 mM) luminal Ca2+ (Calum) or Sr2+ solutions. Bursts of coupled activity (events) started and ended abruptly, with all channels activating/deactivating within ∼300 μs. Coupled RyR1 were heterogeneous, where highly active RyR1 (“drivers”) seemed open during the entire coupled event (Po = 1), while other RyR1s (“followers”) displayed abundant flickering and smaller amplitude. Drivers mean open time increased with cytosolic Ca2+ (Cacyt) or caffeine, whereas followers flicker frequency was Cacyt independent and more sensitive to inhibition by cytosolic Mg2+. Coupled events were insensitive to varying lumen-to-cytosol Ca2+ fluxes from ∼1 to 8 pA, which does not corroborate coupling of neighboring RyR1 by local Ca2+-induced Ca2+ release. However, coupling requires specific Calum sites, as it was lost when Calum was replaced by luminal Ba2+ or Mg2+. In summary, coupled events reveal complex interactions among heterogeneous RyR1, differentially modulated by cytosolic ATP/Mg2+, Cacyt, and Calum, which under cell-like ionic conditions may parallel synchronous RyR1 gating during Ca2+ sparks. PMID:22785120

Localization of PKA Phosphorylation Site, Serine-2030, in the Three-Dimensional Structure of Cardiac Ryanodine Receptor

PubMed Central

Jones, Peter P.; Meng, Xing; Xiao, Bailong; Cai, Shitian; Bolstad, Jeff; Wagenknecht, Terence; Liu, Zheng; Chen, S. R. Wayne

2009-01-01

Protein kinase A (PKA)-dependent phosphorylation of the cardiac Ca2+ release channel/ryanodine receptor (RyR2) is believed to directly dissociate FKBP12.6 from the channel, causing abnormal channel activation and Ca2+ release. To gain insight into the structural basis of the regulation of RyR2 by PKA, we determined the three-dimensional location of the PKA site S2030. Green fluorescent protein (GFP) was inserted into the wild type (wt) RyR2 and RyR2 mutant, A4860G, after T2023. The resultant GFP-RyR2 fusion proteins, RyR2T2023-GFP and RyR2(A4860G)T2023-GFP, were expressed in HEK293 cells and functionally characterized. Ca2+ release assays revealed that both GFP-RyR2 fusion proteins formed caffeine- and ryanodine-sensitive Ca2+ release channels. Further analyses using [3H]ryanodine binding demonstrated that the insertion of GFP into RyR2 wt after T2023 reduced the sensitivity of the channel to activation by Ca2+ or caffeine. RyR2(A4860G)T2023-GFP was found to be structurally more stable than RyR2T2023-GFP and was subsequently used as a basis for three-dimensional reconstruction. Cryo-electron microscopy and single particle image processing of the purified RyR2(A4860G)T2023-GFP protein revealed the location of the inserted GFP, and hence the S2030 PKA site in domain 4, a region that may be involved in signal transduction between the transmembrane and cytoplasmic domains. Like the S2808 PKA site reported previously, the S2030 site is not located close to the FKBP12.6 binding site mapped previously, indicating that neither of these PKA sites is directly involved in FKBP12.6 binding. Based on the three-dimensional localizations of a number of residues or regions, a model for the subunit organization in the structure of RyR2 is proposed. PMID:17967164

Localization of an NH2-Terminal Disease-Causing Mutation Hotspot to the “Clamp” Region in the Three-Dimensional Structure of the Cardiac Ryanodine Receptor

PubMed Central

Wang, Ruiwu; Chen, Wenqian; Cai, Shitian; Zhang, Jing; Bolstad, Jeff; Wagenknecht, Terence; Liu, Zheng; Chen, S. R. Wayne

2009-01-01

A region between residues 414 and 466 in the cardiac ryanodine receptor (RyR2) harbors more than half of the known NH2-terminal mutations associated with cardiac arrhythmias and sudden death. To gain insight into the structural basis of this NH2-terminal mutation hotspot, we have determined its location in the three-dimensional structure of RyR2. Green fluorescent protein (GFP), used as a structural marker, was inserted into the middle of this mutation hotspot after Ser-437 in the RyR2 sequence. The resultant GFP-RyR2 fusion protein, RyR2S437-GFP, was expressed in HEK293 cells and characterized using Ca2+ release, [3H]ryanodine binding, and single cell Ca2+ imaging studies. These functional analyses revealed that RyR2S437-GFP forms a caffeine-and ryanodine-sensitive Ca2+ release channel that possesses Ca2+- and caffeine-dependence of activation indistinguishable from that of wild type (wt) RyR2. HEK293 cells expressing RyR2S437-GFP displayed a propensity for store-overload induced Ca2+ release similar to that in cells expressing RyR2-wt. The three-dimensional structure of the purified RyR2S437-GFP was reconstructed using cryo-electron microscopy and single particle image processing. Subtraction of the three-dimensional reconstructions of RyR2-wt and RyR2S437-GFP revealed the location of the inserted GFP, and hence the NH2-terminal mutation hotspot, in a region between domains 5 and 9 in the clamp-shaped structure. This location is close to a previously mapped central disease-causing mutation site located in a region between domains 5 and 6. These results, together with findings from previous studies, suggest that the proposed interactions between the NH2-terminal and central regions of RyR2 are likely to take place between domains 5 and 6, and that the clamp-shaped structure, which shows substantial conformational differences between the closed and open states, is highly susceptible to disease-causing mutations. PMID:17452324

Calcium-Dependent Energetics of Calmodulin Domain Interactions with Regulatory Regions of the Ryanodine Receptor Type 1 (RyR1)

PubMed Central

Newman, Rhonda A.; Sorensen, Brenda R.; Kilpatrick, Adina M.; Shea, Madeline A.

2014-01-01

Calmodulin (CaM) plays a vital role in calcium homeostasis by allosterically modulating intracellular calcium channels including the homo-tetrameric human Ryanodine Receptor Type 1 (hRyR1). Apo (calcium-free) CaM activates hRyR1 while calcium-saturated CaM inhibits it. Two CaM-binding regions (residues 1975–1999 and 3614–3643) identified in each RyR1 monomer were proposed to allow CaM to bridge adjacent RyR1 subunits. We explored the distinct roles of CaM domains by using fluorescence anisotropy to determine the affinity of CaM1–148 (full-length), CaM1–80 (N-domain) and CaM76–148 (C-domain) for peptides encompassing hRyR1 residues 1975–1999 or 3614–3643. Both CaM1–148 and CaM76–148 associated in a calcium-independent manner with similar affinities for hRyR1(3614–3643)p while CaM1–80 required calcium and bound ~250-fold more weakly. Association of CaM1–148, CaM1–80 and CaM76–148 with hRyR1(1975–1999)p was much less favorable than with hRyR1(3614–3643)p; differences between the two CaM domains were smaller. Equilibrium calcium titrations monitored by steady-state fluorescence demonstrated that both hRyR1 peptides increased the calcium-binding affinity of both CaM domains. These thermodynamic properties support a prior model in which the CaM C-domain associates with RyR1(3614–3643) at low levels of calcium, positioning CaM to rapidly respond to calcium efflux. However, the affinity of the N-domain of CaM for hRyR1(1975–1999)p is insufficient to explain a model in which CaM bridges adjacent RyR1 subunits within the tetramer. This indicates that other protein factors or properties of the tertiary or quaternary structure of hRyR1 contribute to the energetics of CaM-mediated regulation. PMID:25145833

Ryanodine Receptor Calcium Leak in Circulating B-Lymphocytes as a Biomarker in Heart Failure.

PubMed

Kushnir, Alexander; Santulli, Gaetano; Reiken, Steven R; Coromilas, Ellie; Godfrey, Sarah J; Brunjes, Danielle L; Colombo, Paolo C; Yuzefpolskaya, Melana; Sokol, Seth I; Kitsis, Richard N; Marks, Andrew R

2018-03-28

Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2 + is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2 + release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2 + leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2 + release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2 + leak, contributing to myopathy and weakness. Circulating B-lymphocytes express RyR1 and catecholamine responsive signaling cascades, making them a potential surrogate for defects in intracellular Ca2 + handling due to leaky RyR channels in CHF. Methods -Whole blood was collected from patients with CHF, CHF status-post left-ventricular assist devices (LVAD), and controls. Blood was also collected from mice with ischemic CHF, ischemic CHF + S107 (a drug that specifically reduces RyR channel Ca2 + leak), and WT controls. Channel macromolecular complex was assessed by immunostaining RyR1 immunoprecipitated from lymphocyte enriched preparations. RyR1 Ca2 + leak was assessed using flow cytometry to measure Ca2 + fluorescence in B-lymphocytes, in the absence and presence of RyR1 agonists that empty RyR1 Ca2 + stores within the endoplasmic reticulum (ER). Results -Circulating B-lymphocytes from humans and mice with CHF exhibited remodeled RyR1 and decreased ER Ca2 + stores, consistent with chronic intracellular Ca2 + leak. This Ca2 + leak correlated with circulating catecholamine levels. The intracellular Ca2 + leak was significantly reduced in mice treated with the Rycal S107. CHF patients treated with LVAD exhibited a heterogeneous response. Conclusions -In CHF, B-lymphocytes exhibit remodeled leaky RyR1 channels and decreased ER Ca2 + stores consistent with chronic intracellular Ca2 + leak. RyR1 mediated Ca2 + leak in B-lymphocytes assessed using flow cytometry provides a surrogate measure of intracellular Ca2 + handling and systemic sympathetic burden, presenting a novel biomarker for monitoring response to pharmacologic and mechanical CHF therapy.

RR Lyrae, Delta Scuti, SX Phoenicis stars and Baade-Wesselink method. I - Photometric and radial velocity measurements of four field stars - RR Cet, DX Del, BS AQR and DY Peg

NASA Astrophysics Data System (ADS)

Meylan, G.; Burki, G.; Rufener, F.; Mayor, M.; Burnet, M.; Ischi, E.

1986-04-01

Simultaneous measurements in the Geneva seven-color photometry and in radial velocities with the spectrophotometer CORAVEL for two RR Lyrae, one Delta Scuti and one SX Phoenicis field star were obtained in order to apply the Baade-Wesselink method to these kinds of variable stars. As a first step, the data regarding the RR Cet, DX Del, BS Aqr, and DY Peg are presented. The target of this study will consist in determining the physical parameters (temperature, gravity, metal content, mass, luminosity) and distances of these stars.

Core overshoot and convection in δ Scuti and γ Doradus stars

NASA Astrophysics Data System (ADS)

Lovekin, Catherine; Guzik, Joyce A.

2017-09-01

The effects of rotation on pulsation in δ Scuti and γ Doradus stars are poorly understood. Stars in this mass range span the transition from convective envelopes to convective cores, and realistic models of convection are thus a key part of understanding these stars. In this work, we use 2D asteroseismic modelling of 5 stars observed with the Kepler spacecraft to provide constraints on the age, mass, rotation rate, and convective core overshoot. We use Period04 to calculate the frequencies based on short cadence Kepler observations of five γ Doradus and δ Scuti stars. We fit these stars with rotating models calculated using MESA and adiabatic pulsation frequencies calculated with GYRE. Comparison of these models with the pulsation frequencies of three stars observed with Kepler allowed us to place constraints on the age, mass, and rotation rate of these stars. All frequencies not identified as possible combinations were compared to theoretical frequencies calculated using models including the effects of rotation and overshoot. The best fitting models for all five stars are slowly rotating at the best fitting age and have moderate convective core overshoot. In this work, we will discuss the results of the frequency extraction and fitting process.

Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition.

PubMed

Willemse, Hermia; Theodoratos, Angelo; Smith, Paul N; Dulhunty, Angela F

2016-02-01

The skeletal muscle ryanodine receptor Ca(2+) release channel (RyR1), essential for excitation-contraction (EC) coupling, demonstrates a known developmentally regulated alternative splicing in the ASI region. We now find unexpectedly that the expression of the splice variants is closely related to fiber type in adult human lower limb muscles. We examined the distribution of myosin heavy chain isoforms and ASI splice variants in gluteus minimus, gluteus medius and vastus medialis from patients aged 45 to 85 years. There was a strong positive correlation between ASI(+)RyR1 and the percentage of type 2 fibers in the muscles (r = 0.725), and a correspondingly strong negative correlation between the percentages of ASI(+)RyR1 and percentage of type 1 fibers. When the type 2 fiber data were separated into type 2X and type 2A, the correlation with ASI(+)RyR1 was stronger in type 2X fibers (r = 0.781) than in type 2A fibers (r = 0.461). There was no significant correlation between age and either fiber-type composition or ASI(+)RyR1/ASI(-)RyR1 ratio. The results suggest that the reduced expression of ASI(-)RyR1 during development may reflect a reduction in type 1 fibers during development. Preferential expression of ASI(-) RyR1, having a higher gain of in Ca(2+) release during EC coupling than ASI(+)RyR1, may compensate for the reduced terminal cisternae volume, fewer junctional contacts and reduced charge movement in type 1 fibers.

Association of cardiac myosin binding protein-C with the ryanodine receptor channel: putative retrograde regulation?

PubMed

Stanczyk, Paulina J; Seidel, Monika; White, Judith; Viero, Cedric; George, Christopher H; Zissimopoulos, Spyros; Lai, F Anthony

2018-06-21

The cardiac muscle ryanodine receptor-Ca 2+ release channel (RyR2) constitutes the sarcoplasmic reticulum (SR) Ca 2+ efflux mechanism that initiates myocyte contraction, while cardiac myosin binding protein-C (cMyBP-C) mediates regulation of acto-myosin cross-bridge cycling. In this report, we provide the first evidence for the presence of direct interaction between these two proteins, forming a RyR2:cMyBP-C complex. The C-terminus of cMyBP-C binds with the RyR2 N-terminus in mammalian cells and is not mediated by a fibronectin-like domain. Notably, we detected complex formation between both recombinant cMyBP-C and RyR2, as well as with the native proteins in cardiac tissue. Cellular Ca 2+ dynamics in HEK293 cells is altered upon co-expression of cMyBP-C and RyR2, with lowered frequency of RyR2-mediated spontaneous Ca 2+ oscillations, suggesting cMyBP-C exerts a potential inhibitory effect on RyR2-dependent Ca 2+ release. Discovery of a functional RyR2 association with cMyBP-C provides direct evidence for a putative mechanistic link between cytosolic soluble cMyBP-C and SR-mediated Ca 2+ release, via RyR2. Importantly, this interaction may have clinical relevance to the observed cMyBP-C and RyR2 dysfunction in cardiac pathologies, such as hypertrophic cardiomyopathy. © 2018. Published by The Company of Biologists Ltd.

High-Throughput Screens to Discover Small-Molecule Modulators of Ryanodine Receptor Calcium Release Channels

PubMed Central

Rebbeck, Robyn T.; Essawy, Maram M.; Nitu, Florentin R.; Grant, Benjamin D.; Gillispie, Gregory D.; Thomas, David D.; Bers, Donald M.; Cornea, Razvan L.

2017-01-01

Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca2+ channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca2+ regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca2+], increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes and neurological disorders. This leaky state of the RyR is an attractive target for pharmacological agents to treat such pathologies. Our FRET-based HTS detects RyR binding of accessory proteins calmodulin or FKBP12.6. Under conditions that mimic a pathological state, we carried out a screen of the 727-compound NIH Clinical Collection, which yielded six compounds that reproducibly changed FRET by >3SD. Dose-response of FRET and [3H]ryanodine binding readouts reveal that five hits reproducibly alter RyR1 structure and activity. One compound increased FRET and inhibited RyR1, which was only significant at nM [Ca2+], and accentuated without CaM present. These properties characterize a compound that could mitigate RyR1 leak. An excellent z′-factor and the tight correlation between structural and functional readouts validate this first HTS method to identify RyR modulators. PMID:27760856

Heterogeneous gene expression and functional activity of ryanodine receptors in resistance and conduit pulmonary as well as mesenteric artery smooth muscle cells.

PubMed

Zheng, Yun-Min; Wang, Qing-Song; Liu, Qing-Hua; Rathore, Rakesh; Yadav, Vishal; Wang, Yong-Xiao

2008-01-01

Hypoxia causes heterogeneous contractile responses in resistance and conduit pulmonary as well as systemic (mesenteric) artery smooth muscle cells (RPASMCs, CPASMCs and MASMCs), but the underlying mechanisms are largely unknown. In this study, we aimed to investigate whether the gene expression and functional activity of ryanodine receptors (RyRs) would be different in these 3 cell types. RyR mRNA expression, Ca(2+) sparks and [Ca(2+)](i) were measured by real-time quantitative RT-PCR, laser scanning confocal microscopy and wide-field fluorescence microscopy, respectively. All 3 RyR subtype (RyR1, RyR2 and RyR3) mRNAs are expressed in RPASMCs, CPASMCs and MASMCs, but their expression levels are different. Spontaneous Ca(2+) sparks (functional events of RyRs) show distinct frequency, amplitude, duration, size and kinetics in these 3 cell types. Similarly, activation of RyRs by caffeine, 4-chloro-m-cresol or high K(+) induces differential Ca(2+) release. Moreover, hypoxia-induced increase in [Ca(2+)](i) is largest in MASMCs relative to CPSAMCs and smallest in RPASMCs. This study provides comprehensive evidence that RyRs are heterogeneous in gene expression and functional activity in RPASMCs, CPASMCs and MASMCs, which may contribute to the diversity of excitation-contraction coupling and hypoxic Ca(2+) responses in different vascular smooth muscle cells. Copyright 2008 S. Karger AG, Basel.

The RY/Sph element mediates transcriptional repression of maturation genes from late maturation to early seedling growth.

PubMed

Guerriero, Gea; Martin, Nathalie; Golovko, Anna; Sundström, Jens F; Rask, Lars; Ezcurra, Ines

2009-11-01

In orthodox seeds, the transcriptional activator ABI3 regulates two major stages in embryo maturation: a mid-maturation (MAT) stage leading to accumulation of storage compounds, and a late maturation (LEA) stage leading to quiescence and desiccation tolerance. Our aim was to elucidate mechanisms for transcriptional shutdown of MAT genes during late maturation, to better understand phase transition between MAT and LEA stages. Using transgenic and transient approaches in Nicotiana, we examined activities of two ABI3-dependent reporter genes driven by multimeric RY and abscisic acid response elements (ABREs) from a Brassica napus napin gene, termed RY and ABRE, where the RY reporter requires ABI3 DNA binding. Expression of RY peaks during mid-maturation and drops during late maturation, mimicking the MAT gene program, and in Arabidopsis thaliana RY elements are over-represented in MAT, but not in LEA, genes. The ABI3 transactivation of RY is inhibited by staurosporine, by a PP2C phosphatase, and by a repressor of maturation genes, VAL1/HSI2. The RY element mediates repression of MAT genes, and we propose that transcriptional shutdown of the MAT program during late maturation involves inhibition of ABI3 DNA binding by dephosphorylation. Later, during seedling growth, VAL1/HSI2 family repressors silence MAT genes by binding RY elements.

The VHCF experimental investigation of FV520B-I with surface roughness Ry

NASA Astrophysics Data System (ADS)

Wang, J. L.; Zhang, Y. L.; Ding, M. C.; Zhao, Q. C.

2018-05-01

Different surface roughness type (Ra and Ry) has different effect on the VHCF failure and life. Ra is widely employed as the quantitative expression of the surface roughness, but there are few fatigue failure mechanism analysis and experimental study under surface roughness Ry. The VHCF experiment is conducted out using the specimen with different surface roughness values. The surface roughness Ry is employed as the major research object to investigate the relationship and distribution tendency between the Ry, fatigue life and the distance between internal inclusion and surface, and a new VHCF failure character is proposed.

Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain

PubMed Central

Huang, Xiaojun; Liu, Ying; Wang, Ruiwu; Zhong, Xiaowei; Liu, Yingjie; Koop, Andrea; Chen, S. R. Wayne; Wagenknecht, Terence; Liu, Zheng

2013-01-01

Summary Calmodulin (CaM), a 16 kDa ubiquitous calcium-sensing protein, is known to bind tightly to the calcium release channel/ryanodine receptor (RyR), and modulate RyR function. CaM binding studies using RyR fragments or synthetic peptides have revealed the presence of multiple, potential CaM-binding regions in the primary sequence of RyR. In the present study, we inserted GFP into two of these proposed CaM-binding sequences and mapped them onto the three-dimensional structure of intact cardiac RyR2 by cryo-electron microscopy. Interestingly, we found that the two potential CaM-binding regions encompassing, Arg3595 and Lys4269, respectively, are in close proximity and are adjacent to the previously mapped CaM-binding sites. To monitor the conformational dynamics of these CaM-binding regions, we generated a fluorescence resonance energy transfer (FRET) pair, a dual CFP- and YFP-labeled RyR2 (RyR2R3595-CFP/K4269-YFP) with CFP inserted after Arg3595 and YFP inserted after Lys4269. We transfected HEK293 cells with the RyR2R3595-CFP/K4269-YFP cDNA, and examined their FRET signal in live cells. We detected significant FRET signals in transfected cells that are sensitive to the channel activator caffeine, suggesting that caffeine is able to induce conformational changes in these CaM-binding regions. Importantly, no significant FRET signals were detected in cells co-transfected with cDNAs encoding the single CFP (RyR2R3595-CFP) and single YFP (RyR2K4269-YFP) insertions, indicating that the FRET signal stemmed from the interaction between R3595–CFP and K4269–YFP that are in the same RyR subunit. These observations suggest that multiple regions in the RyR2 sequence may contribute to an intra-subunit CaM-binding pocket that undergoes conformational changes during channel gating. PMID:23868982

The elusive role of the SPRY2 domain in RyR1

PubMed Central

Willemse, Hermia; Mirza, Shamaruh; Gallant, Esther M; Board, Philip G

2011-01-01

The second of three SPRY domains (SPRY2, S1085-V1208) located in the skeletal muscle ryanodine receptor (RyR1) is contained within regions of RyR1 that influence EC coupling and bind to imperatoxin A, a toxin probe of RyR1 channel gating. We examined the binding of the F loop (P1107-A1121) in SPRY2 to the ASI/basic region in RyR1 (T3471-G3500, containing both alternatively spliced (ASI) residues and neighboring basic amino acids). We then investigated the possible influence of this interaction on excitation contraction (EC) coupling. A peptide with the F loop sequence and an antibody to the SPRY2 domain each enhanced RyR1 activity at low concentrations and inhibited at higher concentrations. A peptide containing the ASI/basic sequence bound to SPRY2 and binding decreased ∼10-fold following mutation or structural disruption of the basic residues. Binding was abolished by mutation of three critical acidic F loop residues. Together these results suggest that the ASI/basic and SPRY2 domains interact in an F loop regulatory module. Although a region that includes the SPRY2 domain influences EC coupling, as does the ASI/basic region, Ca2+ release during ligand- and depolarization-induced RyR1 activation were not altered by mutation of the three critical F loop residues following expression of mutant RyR1 in RyR1-null myotubes. Therefore the electrostatic regulatory interaction between the SPRY2 F loop residues (that bind to imperatoxin A) and the ASI/basic residues of RyR1 does not influence bi-directional DHPR-RyR1 signaling during skeletal EC coupling, possibly because the interaction is interrupted by the influence of factors present in intact muscle cells. PMID:21239886

ß-Adrenergic Stimulation Increases RyR2 Activity via Intracellular Ca2+ and Mg2+ Regulation

PubMed Central

Li, Jiao; Imtiaz, Mohammad S.; Beard, Nicole A.; Dulhunty, Angela F.; Thorne, Rick; vanHelden, Dirk F.; Laver, Derek R.

2013-01-01

Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs) by intracellular Ca2+ and Mg2+ and the role of these changes in SR Ca2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control) and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca2+] <1 µM, ß-adrenergic stimulation increased luminal Ca2+ activation of single RyR channels, decreased luminal Mg2+ inhibition and decreased inhibition of RyRs by mM cytoplasmic Mg2+. At cytoplasmic [Ca2+] >1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg2+ and Ca2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1) increasing the activating potency of Ca2+ binding to the luminal Ca2+ site and decreasing its affinity for luminal Mg2+ and 2) decreasing affinity of the low-affinity Ca2+/Mg2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter. PMID:23533585

Investigating the inter-subunit/subdomain interactions and motions relevant to disease mutations in the N-terminal domain of ryanodine receptors by molecular dynamics simulation.

PubMed

Zheng, Wenjun; Liu, Zheng

2017-09-01

The ryanodine receptors (RyR) are essential to calcium signaling in striated muscles, and numerous disease mutations have been identified in two RyR isoforms, RyR1 in skeletal muscle and RyR2 in cardiac muscle. A deep understanding of the activation/regulation mechanisms of RyRs has been hampered by the shortage of high-resolution structures and dynamic information for this giant tetrameric complex in different functional states. Toward elucidating the molecular mechanisms of disease mutations in RyRs, we performed molecular dynamics simulation of the N-terminal domain (NTD) which is not only the best-resolved structural component of RyRs, but also a hotspot of disease mutations. First, we simulated the tetrameric NTD of wild-type RyR1 and three disease mutants (K155E, R157Q, and R164Q) that perturb the inter-subunit interfaces. Our simulations identified a dynamic network of salt bridges involving charged residues at the inter-subunit/subdomain interfaces and disease-mutation sites. By perturbing this key network, the above three mutations result in greater flexibility with the highest inter-subunit opening probability for R157Q. Next, we simulated the monomeric NTD of RyR2 in the presence or absence of a central Cl - anion which is known to stabilize the interfaces between the three NTD subdomains (A, B, and C). We found that the loss of Cl - restructures the salt-bridge network near the Cl - -binding site, leading to rotations of subdomain A/B relative to subdomain C and enhanced mobility between the subdomains. This finding supports a mechanism for disease mutations in the NTD of RyR2 via perturbation of the Cl - binding. The rich structural and dynamic information gained from this study will guide future mutational and functional studies of the NTD of RyRs. Proteins 2017; 85:1633-1644. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia

PubMed Central

Cerrone, Marina; Noujaim, Sami F.; Tolkacheva, Elena G.; Talkachou, Arkadzi; O’Connell, Ryan; Berenfeld, Omer; Anumonwo, Justus; Pandit, Sandeep V.; Vikstrom, Karen; Napolitano, Carlo; Priori, Silvia G.; Jalife, José

2008-01-01

Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, polymorphic VT, and ventricular fibrillation. Catecholaminergic polymorphic VT is caused by enhanced Ca2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial and endocardial optical mapping, chemical subendocardial ablation with Lugol’s solution, and patch clamping in a knockin (RyR2/RyR2R4496C) mouse model to investigate the arrhythmogenic mechanisms in catecholaminergic polymorphic VT. In isolated hearts, spontaneous ventricular arrhythmias occurred in 54% of 13 RyR2/RyR2R4496C and in 9% of 11 wild-type (P=0.03) littermates perfused with Ca2+ and isoproterenol; 66% of 12 RyR2/RyR2R4496C and 20% of 10 wild-type hearts perfused with caffeine and epinephrine showed arrhythmias (P=0.04). Epicardial mapping showed that monomorphic VT, bidirectional VT, and polymorphic VT manifested as concentric epicardial breakthrough patterns, suggesting a focal origin in the His–Purkinje networks of either or both ventricles. Monomorphic VT was clearly unifocal, whereas bidirectional VT was bifocal. Polymorphic VT was initially multifocal but eventually became reentrant and degenerated into ventricular fibrillation. Endocardial mapping confirmed the Purkinje fiber origin of the focal arrhythmias. Chemical ablation of the right ventricular endocardial cavity with Lugol’s solution induced complete right bundle branch block and converted the bidirectional VT into monomorphic VT in 4 anesthetized RyR2/RyR2R4496C mice. Under current clamp, single Purkinje cells from RyR2/RyR2R4496C mouse hearts generated delayed afterdepolarization–induced triggered activity at lower frequencies and level of adrenergic stimulation than wild-type. Overall, the data demonstrate that the His–Purkinje system is an important source of focal arrhythmias in catecholaminergic polymorphic VT. PMID:17872467

Annotated type catalogue of the Chrysididae (Insecta, Hymenoptera) deposited in the collection of Radoszkowski in the Polish Academy of Sciences, Kraków

PubMed Central

Rosa, Paolo; Wiśniowski, Bogdan; Xu, Zai-fu

2015-01-01

Abstract A critical and annotated catalogue of 183 types of Hymenoptera Chrysididae belonging to 124 taxa housed in the Radoszkowski collection is given. Radoszkowski type material from other institutes has also been checked. Six lectotypes are designated in Kraków (ISEA-PAN): Chrysis acceptabilis Radoszkowski, 1891; Chrysis persica Radoczkowsky, 1881; Chrysis daphnis Mocsáry, 1889; Chrysis lagodechii Radoszkowski, 1889; Chrysis remota Mocsáry, 1889 and Chrysis vagans Radoszkowski, 1877. The lectotype of Brugmoia pellucida Radoszkowski, 1877 is designated in Moscow (MMU). Four new combinations are proposed: Philoctetes araraticus (Radoszkowski, 1890), comb. n.; Pseudomalus hypocrita (du Buysson, 1893), comb. n.; Chrysis eldari (Radoszkowski, 1893), comb. n.; and Chrysura mlokosewitzi (Radoszkowski, 1889), comb. n.. Ten new synonyms are given: Chrysis auropunctata Mocsáry, 1889, syn. n. of Chrysis angolensis Radoszkovsky, 1881; Chrysis chrysochlora Mocsáry, 1889, syn. n. and Chrysis viridans Radoszkowski, 1891, syn. n. of Chrysis keriensis Radoszkowski, 1887; Chrysis angustifrons var. ignicollis Trautmann, 1926, syn. n. of Chrysis eldari (Radoszkowski, 1893); Chrysis maracandensis var. simulatrix Radoszkowski, 1891, syn. n. of Chrysis maracandensis Radoszkowski, 1877; Chrysis pulchra Radoszkovsky, 1880, syn. n. of Spinolia dallatorreana (Mocsáry, 1896); Chrysis rubricollis du Buysson, 1900, syn. n. of Chrysis eldari (Radoszkowski, 1893); Chrysis subcoerulea Radoszkowski, 1891, syn. n. of Chrysis chlorochrysa Mocsáry, 1889; Chrysis therates Mocsáry, 1889, syn. n. of Chrysis principalis Smith, 1874; and Notozus komarowi Radoszkowski, 1893, syn. n. of Elampus obesus (Mocsáry, 1890). One species is revaluated: Chrysis chalcochrysa Mocsáry, 1887. Chrysis kizilkumiana Rosa is the new name for Chrysis uljanini Radoszkowski & Mocsáry, 1889 nec Radoszkowski, 1877. Pictures of seventy-seven type specimens are given. PMID:25829848

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.

PubMed

Bussiere, Renaud; Lacampagne, Alain; Reiken, Steven; Liu, Xiaoping; Scheuerman, Valerie; Zalk, Ran; Martin, Cécile; Checler, Frederic; Marks, Andrew R; Chami, Mounia

2017-06-16

Alteration of ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca 2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca 2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca 2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca 2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca 2+ leakage may be a therapeutic approach to treat AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+

PubMed Central

Rybalchenko, Volodymyr; Grillo, Michael A.; Gastinger, Matthew J.; Rybalchenko, Nataliya; Payne, Andrew J.; Koulen, Peter

2010-01-01

Ca2+ release from intracellular stores mediated by endoplasmic reticulum membrane ryanodine receptors (RyR) plays a key role in activating and synchronizing downstream Ca2+-dependent mechanisms, in different cells varying from apoptosis to nuclear transcription and development of defensive responses. Recently discovered, atypical “non-genomic” effects mediated by estrogen receptors (ER) include rapid Ca2+ release upon estrogen exposure in conditions implicitly suggesting involvement of RyRs. In the present study, we report various levels of co-localization between RyR type 2 (RyR2) and ER type β (ERβ) in the neuronal cell line HT-22, indicating a possible functional interaction. Electrophysiological analyses revealed a significant increase in single channel ionic currents generated by mouse brain RyRs after application of the soluble monomer of the long form ERβ (ERβ1). The effect was due to a strong increase in open probability of RyR higher open channel sublevels at cytosolic [Ca2+] concentrations of 100 nM, suggesting a synergistic action of ERβ1 and Ca2+ in RyR activation, and a potential contribution to Ca2+-induced Ca2+ release rather than to basal intracellular Ca2+ concentration level at rest. This RyR/ERβ interaction has potential effects on cellular physiology, including roles of shorter ERβ isoforms and modulation of the RyR/ERβ complexes by exogenous estrogens. PMID:19899956

Calexcitin interaction with neuronal ryanodine receptors.

PubMed Central

Nelson, T J; Zhao, W Q; Yuan, S; Favit, A; Pozzo-Miller, L; Alkon, D L

1999-01-01

Calexcitin (CE), a Ca2+- and GTP-binding protein, which is phosphorylated during memory consolidation, is shown here to co-purify with ryanodine receptors (RyRs) and bind to RyRs in a calcium-dependent manner. Nanomolar concentrations of CE released up to 46% of the 45Ca label from microsomes preloaded with 45CaCl2. This release was Ca2+-dependent and was blocked by antibodies against the RyR or CE, by the RyR inhibitor dantrolene, and by a seven-amino-acid peptide fragment corresponding to positions 4689-4697 of the RyR, but not by heparin, an Ins(1,4,5)P3-receptor antagonist. Anti-CE antibodies, in the absence of added CE, also blocked Ca2+ release elicited by ryanodine, suggesting that the CE and ryanodine binding sites were in relative proximity. Calcium imaging with bis-fura-2 after loading CE into hippocampal CA1 pyramidal cells in hippocampal slices revealed slow, local calcium transients independent of membrane depolarization. Calexcitin also released Ca2+ from liposomes into which purified RyR had been incorporated, indicating that CE binding can be a proximate cause of Ca2+ release. These results indicated that CE bound to RyRs and suggest that CE may be an endogenous modulator of the neuronal RyR. PMID:10393102

miRNAs regulated overexpression of ryanodine receptor is involved in chlorantraniliprole resistance in Plutella xylostella (L.)

PubMed Central

Li, Xiuxia; Guo, Lei; Zhou, Xuguo; Gao, Xiwu; Liang, Pei

2015-01-01

The amino acid mutations in ryanodine receptor (RyR) and elevated activity of detoxification enzymes have been associated with the diamide insecticide resistance in the diamondback moth, Plutella xylostella (L.). The up-regulation of P. xylostella RyR mRNA (PxRyR) expression has also been reported in field populations of different graphical origin. However, whether the up-regulation of PxRyR is involved in diamide resistance remains unknown. In this paper, 2.28- to 4.14-fold higher expression of PxRyR was detected in five field collected resistant populations, compared to that in a susceptible population. The expression of PxRyR was up-regulated 5.0- and 7.2-fold, respectively, after P. xylostella was treated with LC50 and LC75 of chlorantraniliprole for 12 h. Suppression of PxRyR using RNA interference restored the toxicity of chlorantraniliprole against the fourth instar larvae from the resistant population. More importantly, the expression of PxRyR is regulated by two miRNAs, miR-7a and miR-8519. These findings provide an empirical evidence of the involvement of miRNAs in the regulation of insecticide resistance, and shed light on the novel targets for the sustainable management of this devastating insect pest. PMID:26370154

Constraints on pre-main-sequence evolution from stellar pulsations

NASA Astrophysics Data System (ADS)

Casey, M. P.; Zwintz, K.; Guenther, D. B.

2014-02-01

Pulsating pre-main-sequence (PMS) stars afford the earliest opportunity in the lifetime of a star to which the concepts of asteroseismology can be applied. PMS stars should be structurally simpler than their evolved counterparts, thus (hopefully!) making any asteroseismic analysis relatively easier. Unfortunately, this isn't necessarily the case. The majority of these stars (around 80) are δ Scuti pulsators, with a couple of γ Doradus, γ Doradus - δ Scuti hybrids, and slowly pulsating B stars thrown into the mix. The majority of these stars have only been discovered within the last ten years, with the community still uncovering the richness of phenomena associated with these stars, many of which defy traditional asteroseismic analysis. A systematic asteroseismic analysis of all of the δ Scuti PMS stars was performed in order to get a better handle on the properties of these stars as a group. Some strange results have been found, including one star pulsating up to the theoretical acoustic cut-off frequency of the star, and a number of stars in which the most basic asteroseismic analysis suggests problems with the stars' positions in the Hertzsprung-Russell diagram. From this we get an idea of the\\break constraints - or lack thereof - that these results can put on PMS stellar evolution.

Equally spaced periods in the δ Scuti star KIC 5123889

NASA Astrophysics Data System (ADS)

Balona, L. A.

2018-03-01

KIC 5123889 was observed by Kepler almost continuously over a 4-yr period in long-cadence mode. The periodogram shows 14 low-frequency peaks spaced at almost exactly equidistant periods that are shown to be dipole gravity modes. Because the period spacing is practically constant, it can be deduced that the internal rotation period is probably in excess of 1 yr, allowing non-rotating models to be used for frequency matching. For a given metallicity and overshoot parameter, there is a strong correlation between the period spacing and the effective temperature in models covering the main-sequence band. The periods of all 14 dipole modes can be matched with the models to a precision of about 0.1 per cent. In addition, 51 peaks with frequencies in the range 1.7-2.8 d-1 are identified as combinations of the dipole mode frequencies. Four peaks in the frequency range 12.7-18.5 d-1, two of which have high amplitudes, identify the star as a δ Scuti. An attempt to fit the high frequencies using the restrictions imposed by the dipole gravity modes is not convincing as no unique identification can be made. Combination frequencies involving the δ Scuti frequencies and the dipole modes are also present.

Chronic diabetes increases advanced glycation end products on cardiac ryanodine receptors/calcium-release channels.

PubMed

Bidasee, Keshore R; Nallani, Karuna; Yu, Yongqi; Cocklin, Ross R; Zhang, Yinong; Wang, Mu; Dincer, U Deniz; Besch, Henry R

2003-07-01

Decrease in cardiac contractility is a hallmark of chronic diabetes. Previously we showed that this defect results, at least in part, from a dysfunction of the type 2 ryanodine receptor calcium-release channel (RyR2). The mechanism(s) underlying RyR2 dysfunction is not fully understood. The present study was designed to determine whether non-cross-linking advanced glycation end products (AGEs) on RyR2 increase with chronic diabetes and if formation of these post-translational complexes could be attenuated with insulin treatment. Overnight digestion of RyR2 from 8-week control animals (8C) with trypsin afforded 298 peptides with monoisotopic mass (M+H(+)) >or=500. Digestion of RyR2 from 8-week streptozotocin-induced diabetic animals (8D) afforded 21% fewer peptides, whereas RyR2 from 6-week diabetic/2-week insulin-treated animals generated 304 peptides. Using an in-house PERLscript algorithm, search of matrix-assisted laser desorption ionization-time of flight mass data files identified several M+H(+) peaks corresponding to theoretical RyR2 peptides with single N(epsilon)-(carboxymethyl)-lysine, imidazolone A, imidazone B, pyrraline, or 1-alkyl-2-formyl-3,4-glycosyl pyrrole modification that were present in 8D but not 8C. Insulin treatment minimized production of some of these nonenzymatic glycation products. These data show for the first time that AGEs are formed on intracellular RyR2 during diabetes. Because AGE complexes are known to compromise protein activity, these data suggest a potential mechanism for diabetes-induced RyR2 dysfunction.

Crystal structure of ryanodine receptor N-terminal domain from Plutella xylostella reveals two potential species-specific insecticide-targeting sites.

PubMed

Lin, Lianyun; Liu, Chen; Qin, Juan; Wang, Jie; Dong, Shengjie; Chen, Wei; He, Weiyi; Gao, Qingzhi; You, Minsheng; Yuchi, Zhiguang

2018-01-01

Ryanodine receptors (RyRs) are large calcium-release channels located in sarcoplasmic reticulum membrane. They play a central role in excitation-contraction coupling of muscle cells. Three commercialized insecticides targeting pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the structure of insect RyRs remains elusive, hindering our understanding of the mode of action of RyR-targeting insecticides and the development of insecticide resistance in pests. Here we present the crystal structure of RyR N-terminal domain (NTD) (residue 1-205) at 2.84 Å resolution from the diamondback moth (DBM), Plutella xylostella, a destructive pest devouring cruciferous crops all over the world. Similar to its mammalian homolog, DBM RyR NTD consists of a beta-trefoil folding motif and a flanking alpha helix. Interestingly, two regions in NTD interacting with neighboring domains showed distinguished conformations in DBM relative to mammalian RyRs. Using homology modeling and molecular dynamics simulation, we created a structural model of the N-terminal three domains, showing two unique binding pockets that could be targeted by potential species-specific insecticides. Thermal melt experiment showed that the stability of DBM RyR NTD was higher than mammalian RyRs, probably due to a stable intra-domain disulfide bond observed in the crystal structure. Previously DBM NTD was shown to be one of the two critical regions to interact with insecticide flubendiamide, but isothermal titration calorimetry experiments negated DBM NTD alone as a major binding site for flubendiamide. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Variable Stars Discovered by Data Mining Images Taken during Recent Asteroid Photometric Observations. II. Results from July 2015 through December 2016

NASA Astrophysics Data System (ADS)

Papini, R.; Marchini, A.; Salvaggio, F.; Agnetti, D.; Bacci, P.; Banfi, M.; Bianciardi, G.; Collina, M.; Franco, L.; Galli, G.; Milani, M. G. A.; Lopresti, C.; Marino, G.; Rizzuti, L.; Ruocco, N.; Quadri, U.

2017-12-01

This paper follows the previous publication of new variables discovered at Astronomical Observatory, DSFTA, University of Siena, while observing asteroids in order to determine their rotational periods. Usually, this task requires time series images acquisition on a single field for as long as possible on a few nights not necessarily consecutive. Checking continually this "goldmine" allowed us to discover 57 variable stars not yet listed in catalogues or databases. While most of the new variables are eclipsing binaries, a few belong to the RR Lyrae or delta Scuti class. Since asteroid work is definitely a time-consuming activity, coordinated campaigns of follow-up with other observatories have been fundamental in order to determine the elements of the ephemeris and sometimes the right subclass of variability. Further observations of these new variables are therefore strongly encouraged in order to better characterize these stars, especially pulsating ones whose data combined with those taken during professional surveys seem to suggest the presence of light curve amplitude and period variations.

THE TAIWANESE-AMERICAN OCCULTATION SURVEY PROJECT STELLAR VARIABILITY. II. DETECTION OF 15 VARIABLE STARS

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

Mondal, S.; Lin, C. C.; Chen, W. P.

2010-05-15

The Taiwanese-American Occultation Survey (TAOS) project has collected more than a billion photometric measurements since 2005 January. These sky survey data-covering timescales from a fraction of a second to a few hundred days-are a useful source to study stellar variability. A total of 167 star fields, mostly along the ecliptic plane, have been selected for photometric monitoring with the TAOS telescopes. This paper presents our initial analysis of a search for periodic variable stars from the time-series TAOS data on one particular TAOS field, No. 151 (R.A. = 17{sup h}30{sup m}6.{sup s}7, decl. = 27{sup 0}17'30'', J2000), which had beenmore » observed over 47 epochs in 2005. A total of 81 candidate variables are identified in the 3 deg{sup 2} field, with magnitudes in the range 8 < R < 16. On the basis of the periodicity and shape of the light curves, 29 variables, 15 of which were previously unknown, are classified as RR Lyrae, Cepheid, {delta} Scuti, SX Phonencis, semi-regular, and eclipsing binaries.« less

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

The Arrhythmogenic Calmodulin p.Phe142Leu Mutation Impairs C-domain Ca2+ Binding but Not Calmodulin-dependent Inhibition of the Cardiac Ryanodine Receptor*

PubMed Central

Liu, Yingjie; Larsen, Kamilla Taunsig; Nani, Alma; Tian, Xixi; Holt, Christian; Wang, Ruiwu; Fill, Michael

2017-01-01

A number of point mutations in the intracellular Ca2+-sensing protein calmodulin (CaM) are arrhythmogenic, yet their underlying mechanisms are not clear. These mutations generally decrease Ca2+ binding to CaM and impair inhibition of CaM-regulated Ca2+ channels like the cardiac Ca2+ release channel (ryanodine receptor, RyR2), and it appears that attenuated CaM Ca2+ binding correlates with impaired CaM-dependent RyR2 inhibition. Here, we investigated the RyR2 inhibitory action of the CaM p.Phe142Leu mutation (F142L; numbered including the start-Met), which markedly reduces CaM Ca2+ binding. Surprisingly, CaM-F142L had little to no aberrant effect on RyR2-mediated store overload-induced Ca2+ release in HEK293 cells compared with CaM-WT. Furthermore, CaM-F142L enhanced CaM-dependent RyR2 inhibition at the single channel level compared with CaM-WT. This is in stark contrast to the actions of arrhythmogenic CaM mutations N54I, D96V, N98S, and D130G, which all diminish CaM-dependent RyR2 inhibition. Thermodynamic analysis showed that apoCaM-F142L converts an endothermal interaction between CaM and the CaM-binding domain (CaMBD) of RyR2 into an exothermal one. Moreover, NMR spectra revealed that the CaM-F142L-CaMBD interaction is structurally different from that of CaM-WT at low Ca2+. These data indicate a distinct interaction between CaM-F142L and the RyR2 CaMBD, which may explain the stronger CaM-dependent RyR2 inhibition by CaM-F142L, despite its reduced Ca2+ binding. Collectively, these results add to our understanding of CaM-dependent regulation of RyR2 as well as the mechanistic effects of arrhythmogenic CaM mutations. The unique properties of the CaM-F142L mutation may provide novel clues on how to suppress excessive RyR2 Ca2+ release by manipulating the CaM-RyR2 interaction. PMID:27927985

Conformation of ryanodine receptor-2 gates store-operated calcium entry in rat pulmonary arterial myocytes

PubMed Central

Lin, Amanda H.Y.; Sun, Hui; Paudel, Omkar; Lin, Mo-Jun; Sham, James S.K.

2016-01-01

Aims Store-operated Ca2+ entry (SOCE) contributes to a multitude of physiological and pathophysiological functions in pulmonary vasculatures. SOCE attributable to inositol 1,4,5-trisphosphate receptor (InsP3R)-gated Ca2+ store has been studied extensively, but the role of ryanodine receptor (RyR)-gated store in SOCE remains unclear. The present study aims to delineate the relationship between RyR-gated Ca2+ stores and SOCE, and characterize the properties of RyR-gated Ca2+ entry in pulmonary artery smooth muscle cells (PASMCs). Methods and results PASMCs were isolated from intralobar pulmonary arteries of male Wister rats. Application of the RyR1/2 agonist 4-chloro-m-cresol (4-CmC) activated robust Ca2+ entry in PASMCs. It was blocked by Gd3+ and the RyR2 modulator K201 but was unaffected by the RyR1/3 antagonist dantrolene and the InsP3R inhibitor xestospongin C, suggesting RyR2 is mainly involved in the process. siRNA knockdown of STIM1, TRPC1, and Orai1, or interruption of STIM1 translocation with ML-9 significantly attenuated the 4-CmC-induced SOCE, similar to SOCE induced by thapsigargin. However, depletion of RyR-gated store with caffeine failed to activate Ca2+ entry. Inclusion of ryanodine, which itself did not cause Ca2+ entry, uncovered caffeine-induced SOCE in a concentration-dependent manner, suggesting binding of ryanodine to RyR is permissive for the process. This Ca2+ entry had the same molecular and pharmacological properties of 4-CmC-induced SOCE, and it persisted once activated even after caffeine washout. Measurement of Ca2+ in sarcoplasmic reticulum (SR) showed that 4-CmC and caffeine application with or without ryanodine reduced SR Ca2+ to similar extent, suggesting store-depletion was not the cause of the discrepancy. Moreover, caffeine/ryanodine and 4-CmC failed to initiate SOCE in cells transfected with the ryanodine-binding deficient mutant RyR2-I4827T. Conclusions RyR2-gated Ca2+ store contributes to SOCE in PASMCs; however, store-depletion alone is insufficient but requires a specific RyR conformation modifiable by ryanodine binding to activate Ca2+ entry. PMID:27013634

UNEXPECTED SERIES OF REGULAR FREQUENCY SPACING OF δ SCUTI STARS IN THE NON-ASYMPTOTIC REGIME. I. THE METHODOLOGY

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

Paparó, M.; Benkő, J. M.; Hareter, M.

A sequence search method was developed to search the regular frequency spacing in δ Scuti stars through visual inspection and an algorithmic search. We searched for sequences of quasi-equally spaced frequencies, containing at least four members per sequence, in 90 δ Scuti stars observed by CoRoT . We found an unexpectedly large number of independent series of regular frequency spacing in 77 δ Scuti stars (from one to eight sequences) in the non-asymptotic regime. We introduce the sequence search method presenting the sequences and echelle diagram of CoRoT 102675756 and the structure of the algorithmic search. Four sequences (echelle ridges)more » were found in the 5–21 d{sup −1} region where the pairs of the sequences are shifted (between 0.5 and 0.59 d{sup −1}) by twice the value of the estimated rotational splitting frequency (0.269 d{sup −1}). The general conclusions for the whole sample are also presented in this paper. The statistics of the spacings derived by the sequence search method, by FT (Fourier transform of the frequencies), and the statistics of the shifts are also compared. In many stars more than one almost equally valid spacing appeared. The model frequencies of FG Vir and their rotationally split components were used to formulate the possible explanation that one spacing is the large separation while the other is the sum of the large separation and the rotational frequency. In CoRoT 102675756, the two spacings (2.249 and 1.977 d{sup −1}) are in better agreement with the sum of a possible 1.710 d{sup −1} large separation and two or one times, respectively, the value of the rotational frequency.« less

Non-ventricular, Clinical, and Functional Features of the RyR2(R420Q) Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia.

PubMed

Domingo, Diana; Neco, Patricia; Fernández-Pons, Elena; Zissimopoulos, Spyros; Molina, Pilar; Olagüe, José; Suárez-Mier, M Paz; Lai, F Anthony; Gómez, Ana M; Zorio, Esther

2015-05-01

Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca(2+) homeostasis. While the phenotype is characterized by polymorphic ventricular arrhythmias under stress, supraventricular arrhythmias may occur and are not fully characterized. Twenty-five relatives from a Spanish family with several sudden deaths were evaluated with electrocardiogram, exercise testing, and optional epinephrine challenge. Selective RyR2 sequencing in an affected individual and cascade screening in the rest of the family was offered. The RyR2(R420Q) mutation was generated in HEK-293 cells using site-directed mutagenesis to conduct in vitro functional studies. The exercise testing unmasked catecholaminergic polymorphic ventricular tachycardia in 8 relatives (sensitivity = 89%; positive predictive value = 100%; negative predictive value = 93%), all of them carrying the heterozygous RyR2(R420Q) mutation, which was also present in the proband and a young girl without exercise testing, a 91% penetrance at the end of the follow-up. Remarkably, sinus bradycardia, atrial and junctional arrhythmias, and/or giant post-effort U-waves were identified in patients. Upon permeabilization and in intact cells, the RyR2(R420Q) expressing cells showed a smaller peak of Ca(2+) release than RyR2 wild-type cells. However, at physiologic intracellular Ca(2+) concentration, equivalent to the diastolic cytosolic concentration, the RyR2(R420Q) released more Ca(2+) and oscillated faster than RyR2 wild-type cells. The missense RyR2(R420Q) mutation was identified in the N-terminus of the RyR2 gene in this highly symptomatic family. Remarkably, this mutation is associated with sinus bradycardia, atrial and junctional arrhythmias, and giant U-waves. Collectively, functional heterologous expression studies suggest that the RyR2(R420Q) behaves as an aberrant channel, as a loss- or gain-of-function mutation depending on cytosolic intracellular Ca(2+) concentration. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the ryanodine receptor

PubMed Central

Kobayashi, Shigeki; Yano, Masafumi; Suetomi, Takeshi; Ono, Makoto; Tateishi, Hiroki; Mochizuki, Mamoru; Xu, Xiaojuan; Uchinoumi, Hitoshi; Okuda, Shinichi; Yamamoto, Takeshi; Koseki, Noritaka; Kyushiki, Hiroyuki; Ikemoto, Noriaki; Matsuzaki, Masunori

2009-01-01

Objectives To investigate the effect of dantrolene, a drug generally used to treat Malignant Hyperthermia (MH), on the Ca2+ release and cardiomyocyte function in failing hearts. Background The N-terminal (N: 1-600) and Central (C: 2000-2500) domains of the ryanodine receptor (RyR), harbor many mutations associated with MH in skeletal muscle RyR (RyR1) and polymorphic ventricular tachycardia in cardiac RyR (RyR2). There is strong evidence that inter-domain interaction between these regions plays an important role in the mechanism of channel regulation. Methods Sarcoplasmic reticulum (SR) vesicles and cardiomyocytes were isolated from dog LV muscles (normal or rapid ventricular pacing for 4 weeks), for Ca2+ leak, transient, and spark assays. To assess the zipped or unzipped state of the interacting domains, the RyR was fluorescently labeled with methylcoumarin acetate in a site-directed manner. We employed a quartz-crystal microbalance technique to identify the dantrolene binding site within the RyR2. Results Dantrolene specifically bound to domain 601-620 in RyR2. In the SR isolated from pacing-induced dog failing hearts, the defective inter-domain interaction_(domain unzipping) has already occurred, causing spontaneous Ca2+ leak. Dantrolene suppressed both domain unzipping and the Ca2+ leak, showing identical drug concentration-dependence (IC50=0.3 μmol/L). In failing cardiomyocytes, both diastolic Ca2+ sparks and delayed afterdepolarization were frequently observed, but 1 μmol/L dantrolene inhibited both events. Conclusions Dantrolene corrects defective inter-domain interactions within RyR2 in failing hearts, inhibits spontaneous Ca2+ leak, in turn improves cardiomyocyte function in failing hearts. Thus, dantrolene may have a potential to treat heart failure, specifically targeting the RyR2. PMID:19460614

Modulation of Cardiac Ryanodine Receptor Channels by Alkaline Earth Cations

PubMed Central

Diaz-Sylvester, Paula L.; Porta, Maura; Copello, Julio A.

2011-01-01

Cardiac ryanodine receptor (RyR2) function is modulated by Ca2+ and Mg2+. To better characterize Ca2+ and Mg2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M2+: Mg2+, Ca2+, Sr2+, Ba2+) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca2+ or Sr2+. This activation was interfered by Mg2+ and Ba2+ acting at low affinity M2+-unspecific binding sites. When testing the effects of luminal M2+ as current carriers, all M2+ increased maximal RyR2 open probability (compared to Cs+), suggesting the existence of low affinity activating M2+-unspecific sites at the luminal surface. Responses to M2+ vary from channel to channel (heterogeneity). However, with luminal Ba2+or Mg2+, RyR2 were less sensitive to cytosolic Ca2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca2+or Sr2+). Kinetics of RyR2 with mixtures of luminal Ba2+/Ca2+ and additive action of luminal plus cytosolic Ba2+ or Mg2+ suggest luminal M2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca2+/Sr2+-specific sites, which stabilize high Po mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M2+ binding sites (specific for Ca2+ and unspecific for Ca2+/Mg2+) that dynamically modulate channel activity and gating status, depending on SR voltage. PMID:22039534

Selective expression of the type 3 isoform of ryanodine receptor Ca{sup 2+} release channel (RyR3) in a subset of slow fibers in diaphragm and cephalic muscles of adult rabbits

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

Conti, Antonio; Reggiani, Carlo; Sorrentino, Vincenzo

2005-11-11

The expression pattern of the RyR3 isoform of Ca{sup 2+} release channels was analysed by Western blot in neonatal and adult rabbit skeletal muscles. The results obtained show that the expression of the RyR3 isoform is developmentally regulated. In fact, RyR3 expression was detected in all muscles analysed at 2 and 15 days after birth while, in adult animals, it was restricted to a subset of muscles that includes diaphragm, masseter, pterygoideus, digastricus, and tongue. Interestingly, all of these muscles share a common embryonic origin being derived from the somitomeres or from the cephalic region of the embryo. Immunofluorescence analysismore » of rabbit skeletal muscle cross-sections showed that RyR3 staining was detected in all fibers of neonatal muscles. In contrast, in those adult muscles expressing RyR3 only a fraction of fibers was labelled. Staining of these muscles with antibodies against fast and slow myosins revealed a close correlation between expression of RyR3 and fibers expressing slow myosin isoform.« less

Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy

PubMed Central

Pedrozo, Zully; Torrealba, Natalia; Fernández, Carolina; Gatica, Damian; Toro, Barbra; Quiroga, Clara; Rodriguez, Andrea E.; Sanchez, Gina; Gillette, Thomas G.; Hill, Joseph A.; Donoso, Paulina; Lavandero, Sergio

2013-01-01

Time for primary review: 15 days Aims Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ. These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit autophagy result in Danon disease characterized by hypertrophic cardiomyopathy. The ryanodine receptor type 2 (RyR2) plays a key role in cardiomyocyte excitation–contraction and its dysfunction can lead to cardiac failure. Whether RyR2 is degraded by CMA is unknown. Methods and results To induce CMA, cultured neonatal rat cardiomyocytes were treated with geldanamycin (GA) to promote protein degradation through this pathway. GA increased LAMP-2A levels together with its redistribution and colocalization with Hsc70 in the perinuclear region, changes indicative of CMA activation. The inhibition of lysosomes but not proteasomes prevented the loss of RyR2. The recovery of RyR2 content after incubation with GA by siRNA targeting LAMP-2A suggests that RyR2 is degraded via CMA. In silico analysis also revealed that the RyR2 sequence harbours six KFERQ motifs which are required for the recognition Hsc70 and its degradation via CMA. Our data suggest that presenilins are involved in RyR2 degradation by CMA. Conclusion These findings are consistent with a model in which oxidative damage of the RyR2 targets it for turnover by presenilins and CMA, which could lead to removal of damaged or leaky RyR2 channels. PMID:23404999

Ry Horsey | NREL

Science.gov Websites

Ry Horsey Photo of Henry Horsey Ry Horsey Software Developer - Commercial Buildings Energy Modeling the field of commercial building energy modeling. He is particularly interested in the increasing tools to support large-scale commercial building energy modeling. This work has led to contributions to

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

Yuchi, Zhiguang; Lau, Kelvin; Van Petegem, Filip

Ryanodine Receptors (RyRs) are huge Ca{sup 2+} release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain saltmore » bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.« less

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.

Inhibitory ryanodine prevents ryanodine receptor-mediated Ca²⁺ release without affecting endoplasmic reticulum Ca²⁺ content in primary hippocampal neurons.

PubMed

Adasme, Tatiana; Paula-Lima, Andrea; Hidalgo, Cecilia

2015-02-27

Ryanodine is a cell permeant plant alkaloid that binds selectively and with high affinity to ryanodine receptor (RyR) Ca(2+) release channels. Sub-micromolar ryanodine concentrations activate RyR channels while micromolar concentrations are inhibitory. Several reports indicate that neuronal synaptic plasticity, learning and memory require RyR-mediated Ca(2+)-release, which is essential for muscle contraction. The use of micromolar (inhibitory) ryanodine represents a common strategy to suppress RyR activity in neuronal cells: however, micromolar ryanodine promotes RyR-mediated Ca(2+) release and endoplasmic reticulum Ca(2+) depletion in muscle cells. Information is lacking in this regard in neuronal cells; hence, we examined here if addition of inhibitory ryanodine elicited Ca(2+) release in primary hippocampal neurons, and if prolonged incubation of primary hippocampal cultures with inhibitory ryanodine affected neuronal ER calcium content. Our results indicate that inhibitory ryanodine does not cause Ca(2+) release from the ER in primary hippocampal neurons, even though ryanodine diffusion should produce initially low intracellular concentrations, within the RyR activation range. Moreover, neurons treated for 1 h with inhibitory ryanodine had comparable Ca(2+) levels as control neurons. These combined findings imply that prolonged incubation with inhibitory ryanodine, which effectively abolishes RyR-mediated Ca(2+) release, preserves ER Ca(2+) levels and thus constitutes a sound strategy to suppress neuronal RyR function. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of quality of life between Billroth-І and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: A randomized controlled trial.

PubMed

Yang, Kun; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Zhou, Zong-Guang; Hu, Jian-Kun

2017-09-12

Studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) anastomosis are still lacking and inconsistent. The aim of this trial was to compare the quality of life (QoL) of B-I with R-Y reconstruction after curative distal gastrectomy for gastric cancer. A total of 140 patients were randomly assigned to the B-I group (N = 70) and R-Y group (N = 70) with the comparable baseline characteristics. The overall postoperative morbidity rates were 18.6% and 25.7% in the B-I group and R-Y group without significant difference. More estimated blood loss and longer surgical duration were found in the R-Y group. At the postoperative 1 year time point, the B-I group had a higher score in pain, but lower score in global health. However, the R-Y anastomosis was associated with lower incidence of reflux symptoms at postoperative 6 months (P = 0.002) and postoperative 9 months (P = 0.007). The multivariable analyses of variance did not show any interactions between the time trend and grouping. For the results of endoscopic examination, the degree and extent of remnant gastritis were milder significantly in the R-Y group. The stronger anti-reflux capability of R-Y anastomosis contributes to the higher QoL by reducing the reflux related gastritis and pain symptoms, and promotes a better global health.

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.

Progress on research of chicken IgY antibody-FcRY receptor combination and transfer.

PubMed

Tian, Zehua; Zhang, Xiaoying

2012-10-01

The transfer of maternal immunoglobulins (Igs) plays a significant role in fetal initial humoral immunity, of which process has changed and diversified during the evolution of vertebrates. IgY is a key molecular in antibody evolution which links ancient Igs and mammalian Igs such as IgG and IgE. IgY's transfer to the embryo is a two-step receptor-mediated process, including the transfer from the maternal bloodstream to the yolk sac, and from the yolk sac to the embryo. IgY's neonatal Fc receptor (FcRY) mainly functions in the second process. This article reviews IgY's status in antibody evolution and IgY's structure and application. Furthermore, this review compares the binding and transferring mechanism between mammalian IgG, and IgG's neonatal Fc receptor and chicken IgY-FcRY. Details of IgY-FcRY combination, such as combining conditions required, IgY-FcRY binding stoichiometry and exact binding sites on both FcRY and IgY are discussed. Likewise, the endocytosis, the main mechanism of IgY-FcRY transfer and recycling mechanism are analyzed. Related knowledge might be important for better understanding antibody and receptor evolution, antibody-receptor interaction and antibody function. Furthermore, such kind of knowledge might be useful for antibody drug research and development.

Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes.

PubMed

Gonzalez, Daniel R; Beigi, Farideh; Treuer, Adriana V; Hare, Joshua M

2007-12-18

Altered Ca(2+) homeostasis is a salient feature of heart disease, where the calcium release channel ryanodine receptor (RyR) plays a major role. Accumulating data support the notion that neuronal nitric oxide synthase (NOS1) regulates the cardiac RyR via S-nitrosylation. We tested the hypothesis that NOS1 deficiency impairs RyR S-nitrosylation, leading to altered Ca(2+) homeostasis. Diastolic Ca(2+) levels are elevated in NOS1(-/-) and NOS1/NOS3(-/-) but not NOS3(-/-) myocytes compared with wild-type (WT), suggesting diastolic Ca(2+) leakage. Measured leak was increased in NOS1(-/-) and NOS1/NOS3(-/-) but not in NOS3(-/-) myocytes compared with WT. Importantly, NOS1(-/-) and NOS1/NOS3(-/-) myocytes also exhibited spontaneous calcium waves. Whereas the stoichiometry and binding of FK-binding protein 12.6 to RyR and the degree of RyR phosphorylation were not altered in NOS1(-/-) hearts, RyR2 S-nitrosylation was substantially decreased, and the level of thiol oxidation increased. Together, these findings demonstrate that NOS1 deficiency causes RyR2 hyponitrosylation, leading to diastolic Ca(2+) leak and a proarrhythmic phenotype. NOS1 dysregulation may be a proximate cause of key phenotypes associated with heart disease.

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.

Modulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle expressing ryanodine receptor impaired in regulation by calmodulin and S100A1

PubMed Central

Yamaguchi, Naohiro; Prosser, Benjamin L.; Ghassemi, Farshid; Xu, Le; Pasek, Daniel A.; Eu, Jerry P.; Hernández-Ochoa, Erick O.; Cannon, Brian R.; Wilder, Paul T.; Lovering, Richard M.; Weber, David; Melzer, Werner; Schneider, Martin F.

2011-01-01

In vitro, calmodulin (CaM) and S100A1 activate the skeletal muscle ryanodine receptor ion channel (RyR1) at submicromolar Ca2+ concentrations, whereas at micromolar Ca2+ concentrations, CaM inhibits RyR1. One amino acid substitution (RyR1-L3625D) has previously been demonstrated to impair CaM binding and regulation of RyR1. Here we show that the RyR1-L3625D substitution also abolishes S100A1 binding. To determine the physiological relevance of these findings, mutant mice were generated with the RyR1-L3625D substitution in exon 74, which encodes the CaM and S100A1 binding domain of RyR1. Homozygous mutant mice (Ryr1D/D) were viable and appeared normal. However, single RyR1 channel recordings from Ryr1D/D mice exhibited impaired activation by CaM and S100A1 and impaired CaCaM inhibition. Isolated flexor digitorum brevis muscle fibers from Ryr1D/D mice had depressed Ca2+ transients when stimulated by a single action potential. However, during repetitive stimulation, the mutant fibers demonstrated greater relative summation of the Ca2+ transients. Consistently, in vivo stimulation of tibialis anterior muscles in Ryr1D/D mice demonstrated reduced twitch force in response to a single action potential, but greater summation of force during high-frequency stimulation. During repetitive stimulation, Ryr1D/D fibers exhibited slowed inactivation of sarcoplasmic reticulum Ca2+ release flux, consistent with increased summation of the Ca2+ transient and contractile force. Peak Ca2+ release flux was suppressed at all voltages in voltage-clamped Ryr1D/D fibers. The results suggest that the RyR1-L3625D mutation removes both an early activating effect of S100A1 and CaM and delayed suppressing effect of CaCaM on RyR1 Ca2+ release, providing new insights into CaM and S100A1 regulation of skeletal muscle excitation-contraction coupling. PMID:21289290

The Ca2+ leak paradox and “rogue ryanodine receptors”: SR Ca2+ efflux theory and practice

PubMed Central

Sobie, Eric A.; Guatimosim, Silvia; Gómez-Viquez, Leticia; Song, Long-Sheng; Hartmann, Hali; Jafri, M. Saleet; Lederer, W.J.

2006-01-01

Ca2+ efflux from the sarcoplasmic reticulum (SR) is routed primarily through SR Ca2+ release channels (ryanodine receptors, RyRs). When clusters of RyRs are activated by trigger Ca2+ influx through L-type Ca2+ channels (dihydropyridine receptors, DHPR), Ca2+ sparks are observed. Close spatial coupling between DHPRs and RyR clusters and the relative insensitivity of RyRs to be triggered by Ca2+ together ensure the stability of this positive-feedback system of Ca2+ amplification. Despite evidence from single channel RyR gating experiments that phosphorylation of RyRs by protein kinase A (PKA) or calcium-calmodulin dependent protein kinase II (CAMK II) causes an increase in the sensitivity of the RyR to be triggered by [Ca2+]i there is little clear evidence to date showing an increase in Ca2+ spark rate. Indeed, there is some evidence that the SR Ca2+ content may be decreased in hyperadrenergic disease states. The question is whether or not these observations are compatible with each other and with the development of arrhythmogenic extrasystoles that can occur under these conditions. Furthermore, the appearance of an increase in the SR Ca2+ “leak” under these conditions is perplexing. These and related complexities are analyzed and discussed in this report. Using simple mathematical modeling discussed in the context of recent experimental findings, a possible resolution to this paradox is proposed. The resolution depends upon two features of SR function that have not been confirmed directly but are broadly consistent with several lines of indirect evidence: (1) the existence of unclustered or “rogue” RyRs that may respond differently to local [Ca2+]i in diastole and during the [Ca2+]i transient; and (2) a decrease in cooperative or coupled gating between clustered RyRs in response to physiologic phosphorylation or hyperphosphorylation of RyRs in disease states such as heart failure. Taken together, these two features may provide a framework that allows for an improved understanding of cardiac Ca2+ signaling. PMID:16326215

Comparative characterization of two intracellular Ca²⁺-release channels from the red flour beetle, Tribolium castaneum.

PubMed

Liu, Yaping; Li, Chengjun; Gao, Jingkun; Wang, Wenlong; Huang, Li; Guo, Xuezhu; Li, Bin; Wang, Jianjun

2014-10-21

Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are members of a family of tetrameric intracellular Ca(2+)-release channels (CRCs). While it is well known in mammals that RyRs and IP3Rs modulate multiple physiological processes, the roles of these two CRCs in the development and physiology of insects remain poorly understood. In this study, we cloned and functionally characterized RyR and IP3R cDNAs (named TcRyR and TcIP3R) from the red flour beetle, Tribolium castaneum. The composite TcRyR gene contains an ORF of 15,285 bp encoding a protein of 5,094 amino acid residues. The TcIP3R contains an 8,175 bp ORF encoding a protein of 2,724 amino acids. Expression analysis of TcRyR and TcIP3R revealed significant differences in mRNA expression levels among T. castaneum during different developmental stages. When the transcript levels of TcRyR were suppressed by RNA interference (RNAi), an abnormal folding of the adult hind wings was observed, while the RNAi-mediated knockdown of TcIP3R resulted in defective larval-pupal and pupal-adult metamorphosis. These results suggested that TcRyR is required for muscle excitation-contraction (E-C) coupling in T. castaneum, and that calcium release via IP3R might play an important role in regulating ecdysone synthesis and release during molting and metamorphosis in insects.

Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features.

PubMed

Romi, F; Aarli, J A; Gilhus, N E

2007-06-01

Myasthenia gravis (MG) is an autoimmune disease caused in 85% of the patients by acetylcholine receptor (AChR) antibodies. Non-AChR muscle antibodies, against titin and ryanodine receptor (RyR) are mainly found in sera of patients with thymoma or late-onset MG. The occurrence of RyR antibodies increases the risk for severe MG and should lead to active immunomodulating treatment already at MG onset. The aim in this study was to describe the association between symptoms at MG onset and antibody profile in 152 patients. Patients with RyR antibodies had the highest rate of bulbar, respiratory and neck involvement at MG onset. They also had the highest frequency of non-limb MG symptoms. Neck weakness occurred in 40%. Respiratory difficulties at MG onset occurred in patients with titin antibodies, with and without RyR antibodies. Patients with RyR antibodies have a distinctive non-limb MG symptom profile, with bulbar, ocular, neck, and respiratory symptoms. These features, identified as early as at the first examination by a neurologist, characterize the RyR antibody positive subgroup at MG onset.

MALONDIALDEHYDE AND 4-HYDROXYNONENAL ADDUCTS ARE NOT FORMED ON CARDIAC RYANODINE RECEPTOR (RyR2) AND SARCO(ENDO)PLASMIC RETICULUM Ca2+ ATPase (SERCA2) IN DIABETES

PubMed Central

Moore, Caronda J.; Shao, Chun Hong; Nagai, Ryoji; Kutty, Shelby; Singh, Jaipaul; Bidasee, Keshore R.

2013-01-01

Recently, we reported an elevated level of glucose-derived carbonyl adducts on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in hearts of streptozotocin(STZ)-induced diabetic rats. We also showed these adduct impaired RyR2 and SERCA2 activities, and altered evoked Ca2+ transients. What is less clear is if lipid-derived malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) also chemically react with and impair RyR2 and SERCA2 activities in diabetes. This study used Western blot assays with adduct-specific antibodies and confocal microscopy to assess levels of MDA, 4-HNE, Nε-carboxy(methyl)lysine (CML), pentosidine and pyrraline adducts on RyR2 and SERCA2 and evoked intracellular transient Ca2+ kinetics in myocytes from control, diabetic and treated-diabetic rats. MDA and 4-HNE adducts were not detected on RyR2 and SERCA2 from control or 8 weeks diabetic rats with altered evoked Ca2+ transients. However, CML, pentosidine, and pyrraline adducts were elevated 3–5 fold (p<0.05). Treating diabetic rats with pyridoxamine (a scavenger of reactive carbonyl species, RCS) or aminoguanidine (a mixed reactive oxygen species-reactive carbonyl species scavenger) reduced CML, pentosidine and pyrraline adducts on RyR2 and SERCA2 and blunted SR Ca2+ cycling changes. Treating diabetic rats with the superoxide dismutase mimetic tempol had no impact on MDA and 4-HNE adducts on RyR2 and SERCA2, and on SR Ca2+ cycling. From these data we conclude that lipid-derived MDA and 4-HNE adducts are not formed on RyR2 and SERCA2 in this model of diabetes, and are therefore unlikely to be directly contributing to the SR Ca2+ dysregulation. PMID:23354458

Structure of FcRY, an avian immunoglobulin receptor related to mammalian mannose receptors, and its complex with IgY

PubMed Central

He, Yongning; Bjorkman, Pamela J.

2011-01-01

Fc receptors transport maternal antibodies across epithelial cell barriers to passively immunize newborns. FcRY, the functional counterpart of mammalian FcRn (a major histocompatibility complex homolog), transfers IgY across the avian yolk sac, and represents a new class of Fc receptor related to the mammalian mannose receptor family. FcRY and FcRn bind immunoglobulins at pH ≤6.5, but not pH ≥7, allowing receptor–ligand association inside intracellular vesicles and release at the pH of blood. We obtained structures of monomeric and dimeric FcRY and an FcRY–IgY complex and explored FcRY's pH-dependent binding mechanism using electron cryomicroscopy (cryoEM) and small-angle X-ray scattering. The cryoEM structure of FcRY at pH 6 revealed a compact double-ring “head,” in which the N-terminal cysteine-rich and fibronectin II domains were folded back to contact C-type lectin-like domains 1–6, and a “tail” comprising C-type lectin-like domains 7–8. Conformational changes at pH 8 created a more elongated structure that cannot bind IgY. CryoEM reconstruction of FcRY dimers at pH 6 and small-angle X-ray scattering analysis at both pH values confirmed both structures. The cryoEM structure of the FcRY–IgY revealed symmetric binding of two FcRY heads to the dimeric FcY, each head contacting the CH4 domain of one FcY chain. FcRY shares structural properties with mannose receptor family members, including a head and tail domain organization, multimerization that may regulate ligand binding, and pH-dependent conformational changes. Our results facilitate understanding of immune recognition by the structurally related mannose receptor family and comparison of diverse methods of Ig transport across evolution. PMID:21746914

Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias

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

Borko, Ľubomír; Bauerová-Hlinková, Vladena, E-mail: vladena.bauerova@savba.sk; Hostinová, Eva

2014-11-01

X-ray and solution structures of the human RyR2 N-terminal region were obtained under near-physiological conditions. The structure exhibits a unique network of interactions between its three domains, revealing an important stabilizing role of the central helix. Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2 (amino acids 1–606) is the target of >30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near-physiological conditions, as well as a homology model of the hRyR2 N-terminal region, are presented. The N-terminusmore » is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix (amino acids 410–437) plays a prominent stabilizing role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix (R420W, I419F and I419F/R420W) which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N-terminus adopts a globular shape with a prominent tail that is likely to involve residues 545–606, which are unresolved in the crystal structure. Docking the N-terminal domains into cryo-electron microscopy maps of the closed and open RyR1 conformations reveals C{sup α} atom movements of up to 8 Å upon channel gating, and predicts the location of the leucine–isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surface.« less

Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor.

PubMed

Mei, Yingwu; Xu, Le; Mowrey, David D; Mendez Giraldez, Raul; Wang, Ying; Pasek, Daniel A; Dokholyan, Nikolay V; Meissner, Gerhard

2015-07-10

Type 1 ryanodine receptors (RyR1s) release Ca(2+) from the sarcoplasmic reticulum to initiate skeletal muscle contraction. The role of RyR1-G4934 and -G4941 in the pore-lining helix in channel gating and ion permeation was probed by replacing them with amino acid residues of increasing side chain volume. RyR1-G4934A, -G4941A, and -G4941V mutant channels exhibited a caffeine-induced Ca(2+) release response in HEK293 cells and bound the RyR-specific ligand [(3)H]ryanodine. In single channel recordings, significant differences in the number of channel events and mean open and close times were observed between WT and RyR1-G4934A and -G4941A. RyR1-G4934A had reduced K(+) conductance and ion selectivity compared with WT. Mutations further increasing the side chain volume at these positions (G4934V and G4941I) resulted in reduced caffeine-induced Ca(2+) release in HEK293 cells, low [(3)H]ryanodine binding levels, and channels that were not regulated by Ca(2+) and did not conduct Ca(2+) in single channel measurements. Computational predictions of the thermodynamic impact of mutations on protein stability indicated that although the G4934A mutation was tolerated, the G4934V mutation decreased protein stability by introducing clashes with neighboring amino acid residues. In similar fashion, the G4941A mutation did not introduce clashes, whereas the G4941I mutation resulted in intersubunit clashes among the mutated isoleucines. Co-expression of RyR1-WT with RyR1-G4934V or -G4941I partially restored the WT phenotype, which suggested lessening of amino acid clashes in heterotetrameric channel complexes. The results indicate that both glycines are important for RyR1 channel function by providing flexibility and minimizing amino acid clashes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Expressed ryanodine receptor can substitute for the inositol 1,4,5-trisphosphate receptor in Xenopus laevis oocytes during progesterone-induced maturation.

PubMed

Kobrinsky, E; Ondrias, K; Marks, A R

1995-12-01

Two structurally related forms of intracellular calcium release channels that can mediate the release of intracellular calcium have been identified: the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate receptors (IP3R). Each channel responds to distinct pathways for activation. The IP3R is activated by IP3 and the RyR is thought to be activated by calcium or by another second messenger cADP ribose. It has been proposed that each type of channel subserves a specialized pool of intracellular calcium, and it is not understood why some cell types require more than one form of intracellular calcium release channel. The present study was designed to examine whether the RyR can substitute for the IP3R during oocyte maturation. IP3R expression was inhibited in Xenopus laevis oocytes using antisense oligonucleotides. These oocytes, with reduced levels of IP3R, demonstrated a marked delay in the time course of progesterone-induced maturation. The cloned skeletal muscle RyR1 was then expressed in X. laevis oocytes that were deficient in IP3R. Functional studies showed that the properties of the cloned RyR1, expressed in oocytes, were comparable to those of the native RyR1. X. laevis oocytes deficient in IP3R, but expressing RyR1, were able to undergo progesterone-induced maturation with a time course comparable to that seen in wild-type oocytes when caffeine was used to activate RyR and induce intracellular calcium release. These studies show that RyR1 can substitute for the IP3R as the intracellular calcium release channel required for Xenopus oocyte maturation and that intracellular calcium release is important for controlling the rate of progesterone-induced maturation.

CzeV293 and CzeV581-Two new high-amplitude double-mode delta Scuti stars

NASA Astrophysics Data System (ADS)

Skarka, M.; Cagaš, P.

2016-07-01

We report on the discovery of two high-amplitude double-mode delta Scuti stars in constellations of Hercules and Auriga. The stars were observed photometrically in five and two seasons, respectively. Frequency analysis revealed that both stars show complex pulsation behaviour with two independent modes and several combination peaks. Placing the stars into the Petersen diagram allowed us to identify the pulsation modes as the fundamental and the first overtone. Both stars follow the general trend for F/1O pulsators in the short-period part of the Petersen diagram and turned out to be classical members of HADS group of variables. Using empirical formulae we roughly estimate visual absolute magnitude, intrinsic (B - V) 0 colour index and temperature of the target stars.

Rotational Velocity Determinations for 118 δ Scuti Variables

NASA Astrophysics Data System (ADS)

Bush, Tabitha C.; Hintz, Eric G.

2008-09-01

A calibration method is presented for the determination of projected rotational velocities of 118 δ Scuti variables from FWHM measurements of metal lines near 4500 Å. The calibration relation used was derived from measurements of 29 stars. Of the 44 stars brighter than 8th magnitude and north of -1° declination which did not have values in the Rodríguez catalog (Rodríguez, E., López González, M. J., & López de Coca, P. 2000, A&AS, 144, 469) we present values for 38. In addition, we present new projected rotational velocity, vsin i, values for 10 stars south of -1° or fainter than 8th magnitude for a total of 48 vsin i values for stars with no previously published values.

Regular frequency patterns in the young δ Scuti star HD 261711 observed by the CoRoT and MOST satellites

NASA Astrophysics Data System (ADS)

Zwintz, K.; Fossati, L.; Guenther, D. B.; Ryabchikova, T.; Baglin, A.; Themessl, N.; Barnes, T. G.; Matthews, J. M.; Auvergne, M.; Bohlender, D.; Chaintreuil, S.; Kuschnig, R.; Moffat, A. F. J.; Rowe, J. F.; Rucinski, S. M.; Sasselov, D.; Weiss, W. W.

2013-04-01

Context. The internal structure of pre-main-sequence (PMS) stars is poorly constrained at present. This could change significantly through high-quality asteroseismological observations of a sample of such stars. Aims: We concentrate on an asteroseismological study of HD 261711, a rather hot δ Scuti-type pulsating member of the young open cluster NGC 2264 located at the blue border of the instability region. HD 261711 was discovered to be a PMS δ Scuti star using the time series photometry obtained by the MOST satellite in 2006. Methods: High-precision, time-series photometry of HD 261711 was obtained by the MOST and CoRoT satellites in four separate new observing runs that are put into context with the star's fundamental atmospheric parameters obtained from spectroscopy. Frequency Analysis was performed using Period04. The spectral analysis was performed using equivalent widths and spectral synthesis. Results: With the new MOST data set from 2011/12 and the two CoRoT light curves from 2008 and 2011/12, the δ Scuti variability was confirmed and regular groups of frequencies were discovered. The two pulsation frequencies identified in the data from the first MOST observing run in 2006 are confirmed and 23 new δ Scuti-type frequencies were discovered using the CoRoT data. Weighted average frequencies for each group were determined and are related to l = 0 and l = 1 p-modes. Evidence for amplitude modulation of the frequencies in two groups is seen. The effective temperature (Teff) was derived to be 8600 ± 200 K, log g is 4.1 ± 0.2, and the projected rotational velocity (υsini) is 53 ± 1 km s-1. Using our Teff value and the radius of 1.8 ± 0.5 R⊙ derived from spectral energy distribution (SED) fitting, we get a luminosity log L/L⊙ of 1.20 ± 0.14 which agrees well to the seismologically determined values of 1.65 R⊙ and, hence, a log L/L⊙ of 1.13. The radial velocity of 14 ± 2 km s-1 we derived for HD 261711, confirms the star's membership to NGC 2264. Conclusions: Our asteroseismic models suggest that HD 261711 is a δ Scuti-type star close to the zero-age main sequence (ZAMS) with a mass of 1.8 to 1.9 M⊙. With an age of about 10 million years derived from asteroseismology, the star is either a young ZAMS star or a late PMS star just before the onset of hydrogen-core burning. The observed splittings about the l = 0 and 1 parent modes may be an artifact of the Fourier derived spectrum of frequencies with varying amplitudes. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.Based on data from the MOST satellite, a Canadian Space Agency mission, jointly operated by Microsatellite Systems Canada Inc. (MSCI), formerly part of Dynacon, Inc., the University of Toronto Institute for Aerospace Studies and the University of British Columbia with the assistance of the University of Vienna.Reduced spectra are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/552/A68

Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide.

PubMed

Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

2013-01-01

Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1.

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

Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts.

PubMed

Bidasee, Keshore R; Nallani, Karuna; Henry, Bruce; Dincer, U Deniz; Besch, Henry R

2003-07-01

Alteration in cardiac function is one of the hallmarks of diabetes and in late stage is manifested as a decrease in contractility. While it is established that the release of calcium ions from internal sarcoplasmic reticulum via type 2 ryanodine receptor calcium-release channels (RyR2) is vital for efficient contraction, the relationship between diabetes-induced decrease in cardiac performance and alterations in expression and/or function of RyR2 is not well delineated. The present study was designed to address this question and to determine whether changes to RyR2 induced by chronic diabetes could be minimized with insulin-treatment. When paced at 3.3 Hz (200 beats per minute), hearts from 8-week streptozotocin-induced diabetic rats showed decreased responsiveness to isoproterenol stimulation; +dT/dt and -dT/dt were 56.5 +/- 11.4% and 42.1 +/- 12.1% that of control, respectively. Hearts from 8-week diabetic rats expressed 51.2% less RyR2 than controls, In addition, RyR2 from diabetic rats also showed decreased ability to bind the specific ligand [3H]ryanodine (22.4 +/- 1.8% less [3H]ryanodine per microg of RyR2 protein), suggesting dysfunction. Two-weeks of insulin treatment, initiated after 6 weeks of untreated diabetes was able to minimize loss in function and expression of RyR2. Taken collectively, these data suggest that the decrease in cardiac contractility induced by chronic diabetes results in part from decreases in expression and alteration in function of RyR2 and these changes could be attenuated with insulin treatment.

An Extended Structure–Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors

PubMed Central

Feng, Wei; Zheng, Jing; Dong, Yao; Li, Xueshu; Lehmler, Hans-Joachim; Pessah, Isaac N.

2017-01-01

Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca2+ channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure–activity relationship and a quantitative structure–activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [3H]Ryanodine ([3H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the para-position resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs. PMID:27655348

A Novel Roux-en-Y Reconstruction Involving the Use of Two Circular Staplers after Distal Subtotal Gastrectomy for Gastric Cancer.

PubMed

Hur, Hoon; Ahn, Chang Wook; Byun, Cheul Su; Shin, Ho Jung; Kim, Young Bae; Son, Sang-Yong; Han, Sang-Uk

2017-09-01

Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).

Oxidation of RyR2 Has a Biphasic Effect on the Threshold for Store Overload-Induced Calcium Release.

PubMed

Waddell, Helen M M; Zhang, Joe Z; Hoeksema, Katie J; McLachlan, Julia J; McLay, Janet C; Jones, Peter P

2016-06-07

At the single-channel level, oxidation of the cardiac ryanodine receptor (RyR2) is known to activate and inhibit the channel depending on the level of oxidation. However, the mechanisms through which these changes alter the activity of RyR2 in a cellular setting are poorly understood. In this study, we determined the effect of oxidation on a common form of RyR2 regulation; store overload-induced Ca(2+) release (SOICR). We found that oxidation resulted in concentration and time-dependent changes in the activation threshold for SOICR. Low concentrations of the oxidant H2O2 resulted in a decrease in the threshold for SOICR, which led to an increase in SOICR events. However, higher concentrations of H2O2, or prolonged exposure, reversed these changes and led to an increase in the threshold for SOICR. This increase in the threshold for SOICR in most cells was to such an extent that it led to the complete inhibition of SOICR. Acute exposure to high concentrations of H2O2 led to an initial decrease and then increase in the threshold for SOICR. In the majority of cells the increased threshold could not be reversed by the application of the reducing agent dithiothreitol. Therefore, our data suggest that low levels of RyR2 oxidation increase the channel activity by decreasing the threshold for SOICR, whereas high levels of RyR2 oxidation irreversibly increase the threshold for SOICR leading to an inhibition of RyR2. Combined, this indicates that oxidation regulates RyR2 by the same mechanism as phosphorylation, methylxanthines, and mutations, via changes in the threshold for SOICR. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Autoantibody profile and clinical characteristics in a cohort of Chinese adult myasthenia gravis patients.

PubMed

Hong, Yu; Li, Hai-Feng; Skeie, Geir Olve; Romi, Fredrik; Hao, Hong-Jun; Zhang, Xu; Gao, Xiang; Owe, Jone Furlund; Gilhus, Nils Erik

2016-09-15

Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of rogue ryanodine receptors on Ca2+ sparks in cardiac myocytes

PubMed Central

Chen, Xudong; Feng, Yundi; Tan, Wenchang

2018-01-01

Ca2+ sparks and Ca2+ quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca2+ release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca2+ in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca2+ sparks in cardiac myocytes. Ca2+ quarks and sparks from the stochastic opening of rogue and clustered RyRs are numerically reproduced and agree with experimental measurements. It is found that the stochastic opening Ca2+ release units (CRUs) of clustered RyRs are regulated by free Ca2+ concentration in the JSR lumen (i.e. [Ca2+]lumen). The frequency of spontaneous Ca2+ sparks is remarkably increased by the rogue RyRs opening at high [Ca2+]lumen, but not at low [Ca2+]lumen. Hence, the opening of rogue RyRs contributes to the formation of Ca2+ sparks at high [Ca2+]lumen. The interplay of Ca2+ sparks and Ca2+ quarks has been discussed in detail. This work is of significance to provide insight into understanding Ca2+ release mechanisms in cardiac myocytes. PMID:29515864

Effects of rogue ryanodine receptors on Ca2+ sparks in cardiac myocytes.

PubMed

Chen, Xudong; Feng, Yundi; Huo, Yunlong; Tan, Wenchang

2018-02-01

Ca 2+ sparks and Ca 2+ quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca 2+ release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca 2+ in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca 2+ sparks in cardiac myocytes. Ca 2+ quarks and sparks from the stochastic opening of rogue and clustered RyRs are numerically reproduced and agree with experimental measurements. It is found that the stochastic opening Ca 2+ release units (CRUs) of clustered RyRs are regulated by free Ca 2+ concentration in the JSR lumen (i.e. [Ca 2+ ] lumen ). The frequency of spontaneous Ca 2+ sparks is remarkably increased by the rogue RyRs opening at high [Ca 2+ ] lumen , but not at low [Ca 2+ ] lumen . Hence, the opening of rogue RyRs contributes to the formation of Ca 2+ sparks at high [Ca 2+ ] lumen . The interplay of Ca 2+ sparks and Ca 2+ quarks has been discussed in detail. This work is of significance to provide insight into understanding Ca 2+ release mechanisms in cardiac myocytes.

Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis.

PubMed

Wang, Meng-Meng; Hao, Li-Ying; Guo, Feng; Zhong, Bin; Zhong, Xiao-Mei; Yuan, Jing; Hao, Yi-Fei; Zhao, Shuang; Sun, Xue-Fei; Lei, Ming; Jiao, Guang-Yu

2017-12-01

Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca 2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca 2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca 2+ ] was measured by confocal microscopy and fluorescence spectrophotometry. Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca 2+ ] were significantly decreased in the rat sepsis model compared with controls. Decreased intracellular [Ca 2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017. © 2017 Wiley Periodicals, Inc.

Response of ryanodine receptor channels to Ca2+ steps produced by rapid solution exchange.

PubMed Central

Laver, D R; Curtis, B A

1996-01-01

We used a flow method for Ca2+ activation of sheep cardiac and rabbit skeletal ryanodine receptor (RyR) channels in lipid bilayers, which activated RyRs in < 20 ms and maintained a steady [Ca2+] for 5 s. [Ca2+] was rapidly altered by flowing Ca(2+)-buffered solutions containing 100 or 200 microM Ca2+ from a perfusion tube inserted in the cis, myoplasmic chamber above the bilayer. During steps from 0.1 to 100 microM, [Ca2+] reached 0.3 microM (activation threshold) and 10 microM (maximum Po) in times consistent with predictions of a solution exchange model. Immediately following rapid RyR activation, Po was 0.67 (cardiac) and 0.45 (skeletal) at a holding voltage of +40 mV (cis/trans). Po then declined (at constant [Ca2+]) in 70% of channels (n = 25) with time constants ranging from .5 to 15 s. The mechanism for Po decline, whether it be adaptation or inactivation, was not determined in this study. cis, 2 mM Mg2+ reduced the initial Po for skeletal RyRs to 0.21 and marginally slowed the declining phase. During very rapid falls in [Ca2+] from mM (inhibited) to sub-microM (sub-activating) levels, skeletal RyR did not open. We conclude the RyR gates responsible for Ca(2+)-dependent activation and inhibition of skeletal RyRs can gate independently. Images FIGURE 1 FIGURE 8 PMID:8842211

Short-type single balloon enteroscope for endoscopic retrograde cholangiopancreatography with altered gastrointestinal anatomy

PubMed Central

Yamauchi, Hiroshi; Kida, Mitsuhiro; Okuwaki, Kosuke; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Kikuchi, Hidehiko; Watanabe, Maya; Imaizumi, Hiroshi; Koizumi, Wasaburo

2013-01-01

AIM: To evaluate the effectiveness of a short-type single-balloon-enteroscope (SBE) for endoscopic retrograde cholangiopancreatography (ERCP) in patients with a reconstructed intestine. METHODS: Short-type SBE was developed to perform ERCP in postoperative patients with a reconstructed intestine. Short-type SBE is a direct-viewing endoscope with the following specifications: working length, 1520 mm; total length, 1840 mm; channel diameter, 3.2 mm. In addition, short-type SBE has a water-jet channel. The study group comprised 22 patients who underwent 31 sessions of short-type SBE-assisted ERCP from June 2011 through May 2012. Reconstruction was performed by Billroth-II (B-II) gastrectomy in 6 patients (8 sessions), Roux-en-Y (R-Y) gastrectomy in 14 patients (21 sessions), and R-Y hepaticojejunostomy in 2 patients (2 sessions). We retrospectively studied the rate of reaching the blind end (papilla of Vater or choledochojejunal anastomosis), mean time required to reach the blind end, diagnostic success rate (defined as the rate of successfully imaging the bile and pancreatic ducts), therapeutic success rate (defined as the rate of successfully completing endoscopic treatment), mean procedure time, and complications. RESULTS: Among the 31 sessions of ERCP, the rate of reaching the blind end was 88% in B-II gastrectomy, 91% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The mean time required to reach the papilla was 18.3 min in B-II gastrectomy, 21.1 min in R-Y gastrectomy, and 32.5 min in R-Y hepaticojejunostomy. The diagnostic success rates in all patients and those with an intact papilla were respectively 86% and 86% in B-II gastrectomy, 90% and 87% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. The therapeutic success rates in all patients and those with an intact papilla were respectively 100% and 100% in B-II gastrectomy, 94% and 92% in R-Y gastrectomy, and 100% in R-Y hepaticojejunostomy. Because the channel diameter was 3.2 mm, stone extraction could be performed with a wire-guided basket in 12 sessions, and wire-guided intraductal ultrasonography could be performed in 8 sessions. As for complications, hyperamylasemia (defined as a rise in serum amylase levels to more than 3 times the upper limit of normal) occurred in 1 patient (7 sessions) with a B-II gastrectomy and 4 patients (19 sessions) with an R-Y gastrectomy. After ERCP in patients with an R-Y gastrectomy, 2 patients (19 sessions) had pancreatitis, 1 patient (21 sessions) had gastrointestinal perforation, and 1 patient (19 sessions) had papillary bleeding. Pancreatitis and bleeding were both mild. Gastrointestinal perforation improved after conservative treatment. CONCLUSION: Short-type SBE is effective for ERCP in patients with a reconstructed intestine and allows most conventional ERCP devices to be used. PMID:23555161

GSC4813-0981 = V921 Mon, a new low-amplitude δ Scuti star with variable amplitude

NASA Astrophysics Data System (ADS)

Galeev, A.; Bikmaev, I.; Shimansky, V.; Deminova, N.

2014-11-01

GSC 4813-0981 = V921 Mon is a low-amplitude δ Scuti-type variable with an amplitude of 0.018^m-0.027^m in different bands and a period of 48.5 minutes. The fundamental parameters of the atmosphere and physical characteristics, determined from medium-resolution spectra, are: T_{eff}=8700 K, log g=3.95 dex, [M/H]=0, M=1.7 M_{⊙}, R=2.3 R_{⊙}. We performed a long-term analysis of the variations using a ten-year data set of CCD observations (2003-2013) acquired in BVR with the 1.5-m Russian-Turkish telescope (RTT150, TUBITAK National Observatory). A preliminary result is that the amplitude of the variability changes; it was decreasing during 2003-2008, but is now increasing.

The Baade-Wesselink projection factor of the δ-Scuti stars AI Vel and β Cas

NASA Astrophysics Data System (ADS)

Guiglion, G.; Nardetto, N.; Domiciano de Souza, A.; Mathias, P.; Mourard, D.; Poretti, E.

2012-12-01

The Baade-Wesselink method of distance determination is based on the oscillations of pulsating stars. After determining the angular diameter and the linear radius variations, the distance is derived by a simple ratio. The linear radius variation is measured by integrating the pulsation velocity (hereafter V_{puls}) over one pulsating cycle. However, from observations we have only access to the radial velocity (V_{rad}) because of the projection along the line-of-sight. The projection factor, used to convert the radial velocity into the pulsation velocity, is defined by: p = V_{puls} / V_{rad}. We aim to derive the projection factor for two δ-Scuti stars, the high amplitude pulsator AI Vel and the fast rotator β Cas. The geometric component of the projection factor is derived using a limb-darkening model of the intensity distribution of AI Vel, and a fast rotator model for β Cas. Then, by comparing the radial velocity curves of several spectral lines forming at different levels in the atmosphere, we derive directly the velocity gradient (in a part of the atmosphere of the star) using SOPHIE/OHP data for β Cas and HARPS/ESO data for AI Vel, which is used to derive a dynamical projection factor for both stars. We find p = 1.44 ± 0.05 for AI Vel and p = 1.41 ± 0.25 for β Cas. By comparing Cepheids and δ-Scuti stars, these results bring valuable insights into the dynamical structure of pulsating star atmospheres.

Further observations of the lambda 10830 He line in stars and their significance as a measure of stellar activity

NASA Technical Reports Server (NTRS)

Zirin, H.

1975-01-01

Measurements of the lambda 1030 He line in 198 stars are given along with data on other features in that spectral range. Nearly 80% of all G and K stars show some lambda 10830; of these, half are variable and 1/4 show emission. It was confirmed that lambda 10830 is not found in M stars, is weak in F stars, and is particularly strong in close binaries. The line is found in emission in extremely late M and S stars, along with P gamma, but P gamma is not in emission in G and K stars with lambda 10830 emissions. Variable He emission and Ti I emission are found in the RV Tauri variables R Scuti and U Mon. In R Aqr the Fe XIII coronal line lambda 10747 and a line at lambda 11012 which may be singlet He or La II are found, as well as lambda 10830 and P gamma. The nature of coronas or hot chromospheres in the various stars is discussed. It was concluded that the lambda 10830 intensity must be more or less proportional to the energy deposited in the chromosphere corona by non-thermal processes.

Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.

PubMed

So, Jimmy Bok-Yan; Rao, Jaideepraj; Wong, Andrew Siang-Yih; Chan, Yiong-Huak; Pang, Ning Qi; Tay, Amy Yuh Ling; Yung, Man Yee; Su, Zheng; Phua, Janelle Niam Sin; Shabbir, Asim; Ng, Enders Kwok Wai

2018-02-01

The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.

Biodecolorization of Reactive Yellow-2 by Serratia sp. RN34 Isolated from Textile Wastewater.

PubMed

Najme, Rabia; Hussain, Sabir; Maqbool, Zahid; Imran, Muhammad; Mahmood, Faisal; Manzoor, Hamid; Yasmeen, Tahira; Shehzad, Tanvir

2015-12-01

Remediation of colored textile wastewaters is a matter of interest. In this study, 49 bacteria were isolated from the textile wastewater and tested for their ability to decolorize reactive yellow-2 (RY2) dye. The most efficient isolate, RN34, was identified through amplification, sequencing, and phylogenetic analysis of its 16S rDNA and was designated as Serratia sp. RN34. This bacterium was also found capable of decolorizing other related reactive azo-dyes, including reactive black-5, reactive red-120, and reactive orange-16 but at varying rates. The optimum pH for decolorization of RY2 by the strain RN34 was 7.5 using yeast extract as cosubstrate under static incubation at 30 °C. The strain RN34 also showed potential to decolorize RY2 in the presence of considerable amounts of hexavalent chromium and sodium chloride. A phytotoxicity study demonstrated relatively reduced toxicity of RY2 decolorized products on Vigna radiata plant as compared to the uninoculated RY2 solution.

ATTX961014-1R/Y a.k.a. Sierra Rose: A red skin, yellow flesh cultivar for the specialty/gourmet market

USDA-ARS?s Scientific Manuscript database

ATTX961014-1R/Y is a high yielding, red skin, yellow flesh cultivar which was released by Texas A&M AgriLife Research in 2012. It resulted from a cross of breeding clone A90601-2RDY by the potato cultivar Mazama. ATTX961014-1R/Y is susceptible to Late Blight (Phytopthora infestans), Potato Leaf Roll...

Different Involvement of Type 1, 2, and 3 Ryanodine Receptors in Memory Processes

ERIC Educational Resources Information Center

Galeotti, Nicoletta; Quattrone, Alessandro; Vivoli, Elisa; Norcini, Monica; Bartolini, Alessandro; Ghelardini, Carla

2008-01-01

The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003-9 nmol per mouse intracerebroventricularly [i.c.v.]) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001-1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was…

Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death.

PubMed

Marks, A R

2001-04-01

Calcium (Ca2+) ions are second messengers in signaling pathways in all types of cells. They regulate muscle contraction, electrical signals which determine the cardiac rhythm and cell growth pathways in the heart. In the past decade cDNA cloning has provided clues as to the molecular structure of the intracellular Ca2+ release channels (ryanodine receptors, RyR, and inositol 1,4,5-trisphosphate receptors, IP3R) on the sarcoplasmic and endoplasmic reticulum (SR/ER) and an understanding of how these molecules regulate Ca2+ homeostasis in the heart is beginning to emerge. The intracellular Ca2+ release channels form a distinct class of ion channels distinguished by their structure, size, and function. Both RyRs and IP3Rs have gigantic cytoplasmic domains that serve as scaffolds for modulatory proteins that regulate the channel pore located in the carboxy terminal 10% of the channel sequence. The channels are tetramers comprised of four RyR or IP3R subunits. RyR2 is required for excitation-contraction (EC) coupling in the heart. Using co-sedimentation and co-immunoprecipitation we have defined a macromolecular complex comprised of RyR2, FKBP12.6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein mAKAP. We have shown that protein kinase A (PKA) phosphorylation of RyR2 dissociates FKBP12.6 and regulates the channel open probability (P(o)). In failing human hearts RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+-induced activation.

Comparison of Billroth I and Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: one-year postoperative effects assessed by a multi-institutional RCT.

PubMed

Hirao, Motohiro; Takiguchi, Shuji; Imamura, Hiroshi; Yamamoto, Kazuyoshi; Kurokawa, Yukinori; Fujita, Junya; Kobayashi, Kenji; Kimura, Yutaka; Mori, Masaki; Doki, Yuichiro

2013-05-01

This randomized, controlled trial evaluated the clinical efficacy of Billroth I (BI) and Roux-en-Y (RY) reconstruction at 1 year after distal gastrectomy for gastric cancer. The primary end point was the amount of body weight lost at 1 postoperative year, and secondary end points included other items related to nutritional status such as serum albumin and lymphocyte count, as well as endoscopic examination findings of the remnant stomach and esophagus. Of the 332 patients enrolled, 163 were assigned to the BI group and 169 were randomized to the RY group. The loss in body weight 1 year after surgery did not differ significantly between the BI and RY groups (9.1 % and 9.7 %, respectively, p = 0.39). There were no significant differences in other aspects of nutritional status between the 2 groups. Endoscopic examination 1 year after gastrectomy showed reflux esophagitis in 26 patients (17 %) in the BI group versus 10 patients (6 %) in the RY group (p = 0.0037), while remnant gastritis was observed in 71 patients (46 %) in the BI group versus 44 patients (28 %) in the RY group (p = 0.0013); differences were significant for both conditions. Multivariable analysis showed that the only reconstruction was the independently associated factor with the incidence of reflux esophagitis. RY reconstruction was not superior to BI in terms of body weight change or other aspects of nutritional status at 1 year after surgery, although RY more effectively prevented reflux esophagitis and remnant gastritis after distal gastrectomy.

Prevention of gastroduodenal content reflux and delayed gastric emptying after esophagectomy: gastric tube reconstruction with duodenal diversion plus Roux-en-Y anastomosis.

PubMed

Yano, M; Motoori, M; Tanaka, K; Kishi, K; Miyashiro, I; Shingai, T; Gotoh, K; Noura, S; Takahashi, H; Yamada, T; Ohue, M; Ohigashi, H; Ishikawa, O

2012-04-01

Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction

PubMed Central

Xu, Xiaojuan; Yano, Masafumi; Uchinoumi, Hitoshi; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Tateishi, Hiroki; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Yamamoto, Takeshi; Ikeda, Yasuhiro; Ikemoto, Noriaki; Matsuzaki, Masunori

2010-01-01

Calmodulin (CaM), one of the accessory proteins of the cardiac ryanodine receptor (RyR2), is known to play a significant role in the channel regulation of the RyR2. However, the possible involvement of calmodulin in the pathogenic process of catecholaminergic polymorphic ventricular tachycardia (CPVT) has not been investigated. In this study, we investigated the state of RyR2-bound CaM and channel dysfunctions using a knock-in (KI) mouse model with CPVT-linked RyR2 mutation (R2474S). Without added effectors, the affinity of CaM binding to the RyR2 was indistinguishable between KI and WT hearts. In response to cAMP (1 μmol/L), the RyR2 phosphorylation at Ser2808 increased in both WT and KI hearts to the same extent. However, cAMP caused a significant decrease of the CaM binding affinity in KI hearts, but the affinity was unchanged in WT. Dantrolene restored a normal level of CaM-binding affinity in the cAMP-treated KI hearts, suggesting that defective inter-domain interaction between the N-terminal domain and the central domain of the RyR2 (the target of therapeutic effect of dantrolene) is involved in the cAMP-induced reduction of the CaM binding affinity. In saponin-permeabilized cardiomyocytes, the addition of cAMP increased the frequency of spontaneous Ca2+ sparks to a significantly larger extent in KI cardiomyocytes than in WT cardiomyocytes, whereas the addition of a high concentration of CaM attenuated the aberrant increase of Ca2+ sparks. In conclusion, CPVT mutation causes defective inter-domain interaction, significant reduction in the ability of CaM binding to the RyR2, spontaneous Ca2+ leak, and then lethal arrhythmia. PMID:20226167

Superresolution Modeling of Calcium Release in the Heart

PubMed Central

Walker, Mark A.; Williams, George S.B.; Kohl, Tobias; Lehnart, Stephan E.; Jafri, M. Saleet; Greenstein, Joseph L.; Lederer, W.J.; Winslow, Raimond L.

2014-01-01

Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart is the calcium (Ca2+) spark, which arises from a cluster of ryanodine receptors (RyR). Opening of these RyR clusters is triggered to produce a local, regenerative release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ leak out of the SR is an important process for cellular Ca2+ management, and it is critically influenced by spark fidelity, i.e., the probability that a spontaneous RyR opening triggers a Ca2+ spark. Here, we present a detailed, three-dimensional model of a cardiac Ca2+ release unit that incorporates diffusion, intracellular buffering systems, and stochastically gated ion channels. The model exhibits realistic Ca2+ sparks and robust Ca2+ spark termination across a wide range of geometries and conditions. Furthermore, the model captures the details of Ca2+ spark and nonspark-based SR Ca2+ leak, and it produces normal excitation-contraction coupling gain. We show that SR luminal Ca2+-dependent regulation of the RyR is not critical for spark termination, but it can explain the exponential rise in the SR Ca2+ leak-load relationship demonstrated in previous experimental work. Perturbations to subspace dimensions, which have been observed in experimental models of disease, strongly alter Ca2+ spark dynamics. In addition, we find that the structure of RyR clusters also influences Ca2+ release properties due to variations in inter-RyR coupling via local subspace Ca2+ concentration ([Ca2+]ss). These results are illustrated for RyR clusters based on super-resolution stimulated emission depletion microscopy. Finally, we present a believed-novel approach by which the spark fidelity of a RyR cluster can be predicted from structural information of the cluster using the maximum eigenvalue of its adjacency matrix. These results provide critical insights into CICR dynamics in heart, under normal and pathological conditions. PMID:25517166

An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors.

PubMed

Holland, Erika B; Feng, Wei; Zheng, Jing; Dong, Yao; Li, Xueshu; Lehmler, Hans-Joachim; Pessah, Isaac N

2017-01-01

Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca 2+  channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [ 3 H]Ryanodine ([ 3 H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the para-position resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage.

PubMed

Reilly-O'Donnell, Benedict; Robertson, Gavin B; Karumbi, Angela; McIntyre, Connor; Bal, Wojciech; Nishi, Miyuki; Takeshima, Hiroshi; Stewart, Alan J; Pitt, Samantha J

2017-08-11

Aberrant Zn 2+ homeostasis is associated with dysregulated intracellular Ca 2+ release, resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca 2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca 2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn 2+ in shaping intracellular Ca 2+ release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions, and the direct action of Zn 2+ on RyR2 channel function was examined. Under diastolic conditions, the addition of pathophysiological concentrations of Zn 2+ (≥2 nm) caused dysregulated RyR2-channel openings. Our data also revealed that RyR2 channels are not the only SR Ca 2+ -permeable channels regulated by Zn 2+ Elevating the cytosolic Zn 2+ concentration to 1 nm increased the activity of the transmembrane protein mitsugumin 23 (MG23). The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating, suggesting that in heart failure in which Zn 2+ levels are elevated, RyR2 channels do not gate in a sub-conductance state, but rather MG23-gating becomes more apparent. We also show that in H9C2 cells exposed to ischemic conditions, intracellular Zn 2+ levels are elevated, coinciding with increased MG23 expression. In conclusion, these data suggest that dysregulated Zn 2+ homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Ca 2+ leakage. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

MeRy-B, a metabolomic database and knowledge base for exploring plant primary metabolism.

PubMed

Deborde, Catherine; Jacob, Daniel

2014-01-01

Plant primary metabolites are organic compounds that are common to all or most plant species and are essential for plant growth, development, and reproduction. They are intermediates and products of metabolism involved in photosynthesis and other biosynthetic processes. Primary metabolites belong to different compound families, mainly carbohydrates, organic acids, amino acids, nucleotides, fatty acids, steroids, or lipids. Until recently, unlike the Human Metabolome Database ( http://www.hmdb.ca ) dedicated to human metabolism, there was no centralized database or repository dedicated exclusively to the plant kingdom that contained information on metabolites and their concentrations in a detailed experimental context. MeRy-B is the first platform for plant (1)H-NMR metabolomic profiles (MeRy-B, http://bit.ly/meryb ), designed to provide a knowledge base of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata. MeRy-B contains lists of plant metabolites, mostly primary metabolites and unknown compounds, with information about experimental conditions, the factors studied, and metabolite concentrations for 19 different plant species (Arabidopsis, broccoli, daphne, grape, maize, barrel clover, melon, Ostreococcus tauri, palm date, palm tree, peach, pine tree, eucalyptus, plantain rice, strawberry, sugar beet, tomato, vanilla), compiled from more than 2,300 annotated NMR profiles for various organs or tissues deposited by 30 different private or public contributors in September 2013. Currently, about half of the data deposited in MeRy-B is publicly available. In this chapter, readers will be shown how to (1) navigate through and retrieve data of publicly available projects on MeRy-B website; (2) visualize lists of experimentally identified metabolites and their concentrations in all plant species present in MeRy-B; (3) get primary metabolite list for a particular plant species in MeRy-B; and for a particular tissue (4) find information on a primary metabolite regardless of the species.

Photometric studies of δ Scuti stars. I. IP Virginis

USGS Publications Warehouse

Joner, Michael D.; Hintz, Eric G.; Collier, Matthew W.

1998-01-01

We report 15 new times of maximum light for the δ Scuti star IP Virginis (formerly known as SA 106‐1024). An analysis of all times of maximum light indicates that IP Vir has been decreasing in period at a constant rate of − days day−1. Evidence is also presented that IP Vir is a double‐mode variable with a period ratio of . This period ratio predicts a [Fe/H] value of −0.3. From photometric (uvbyβ) observations, we find a foreground reddening of .008 mag and a metallicity of [Fe/H] = +0.05. It is shown that [Fe/H] = −0.3 is most likely the correct value. Intrinsic ‐ and c1‐values, plotted in a model atmosphere grid, indicate a mean effective temperature, K, and a mean surface gravity, . All of these physical parameters support Landolt's initial conclusion that IP Vir is an ordinary δ Sct star.

Rotational Velocity Determinations for 118 δ Scuti Variables

NASA Astrophysics Data System (ADS)

Bush, Tabitha C.; Hintz, E. G.

2009-01-01

We present a calibration method used for the determination of projected rotational velocities (vsin i) of 118 δ Scuti variables from FWHM measurements of metal lines near 4500 Å. The calibration relation used was derived from measurements of 29 stars. Of the 44 stars brighter than 8th magnitude and north of -1° declination which did not have values in the Rodríguez catalog (Rodríguez, E., López González, M. J., & López de Coca, P. 2000, A&AS, 144, 469), we present values for 38. In addition, we present new vsin i values for 10 stars south of -1° or fainter than 8th magnitude for a total of 48 vsin i values for stars with no previously published values. We acknowledge the Dominion Astrophysical Observatory for making available the 1.2-m and 1.8-m telescopes to aid in this research.

Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass

PubMed Central

Hilliard, Fredrick A.; Steele, Derek S.; Laver, Derek; Yang, Zhaokang; Le Marchand, Sylvain J.; Chopra, Nagesh; Piston, David W.; Huke, Sabine; Knollmann, Björn C.

2009-01-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin. We recently found that the drug flecainide inhibits RyR2 channels and prevents CPVT in mice and humans. Here we compared the effects of flecainide and tetracaine, a known RyR2 inhibitor ineffective in CPVT myocytes, on arrhythmogenic Ca2+ waves and elementary sarcoplasmic reticulum (SR) Ca2+ release events, Ca2+ sparks. In ventricular myocytes isolated from a CPVT mouse model, flecainide significantly reduced spark amplitude and spark width, resulting in a 40% reduction in spark mass. Surprisingly, flecainide significantly increased spark frequency. As a result, flecainide had no significant effect on spark-mediated SR Ca2+ leak or SR Ca2+ content. In contrast, tetracaine decreased spark frequency and spark-mediated SR Ca2+ leak, resulting in a significantly increased SR Ca2+ content. Measurements in permeabilized rat ventricular myocytes confirmed the different effects of flecainide and tetracaine on spark frequency and Ca2+ waves. In lipid bilayers, flecainide inhibited RyR2 channels by open state block, whereas tetracaine primarily prolonged RyR2 closed times. The differential effects of flecainide and tetracaine on sparks and RyR2 gating can explain why flecainide, unlike tetracaine, does not change the balance of SR Ca2+ fluxes. We suggest that the smaller spark mass contributes to flecainide's antiarrhythmic action by reducing the probability of saltatory wave propagation between adjacent Ca2+ release units. Our results indicate that inhibition of the RyR2 open state provides a new therapeutic strategy to prevent diastolic Ca2+ waves resulting in triggered arrhythmias, such as CPVT. PMID:19835880

Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2–harboring clones as main relapse-driving force in childhood ALL

PubMed Central

Morak, Maria; Attarbaschi, Andishe; Fischer, Susanna; Nassimbeni, Christine; Grausenburger, Reinhard; Bastelberger, Stephan; Krentz, Stefanie; Cario, Gunnar; Kasper, David; Schmitt, Klaus; Russell, Lisa J.; Pötschger, Ulrike; Stanulla, Martin; Eckert, Conny; Mann, Georg; Haas, Oskar A.; Panzer-Grümayer, Renate

2014-01-01

The P2RY8-CRLF2 fusion defines a particular relapse-prone subset of childhood acute lymphoblastic leukemia (ALL) in Italian Association of Pediatric Hematology and Oncology Berlin-Frankfurt-Münster (AIEOP-BFM) 2000 protocols. To investigate whether and to what extent different clone sizes influence disease and relapse development, we quantified the genomic P2RY8-CRLF2 fusion product and correlated it with the corresponding CRLF2 expression levels in patients enrolled in the BFM-ALL 2000 protocol in Austria. Of 268 cases without recurrent chromosomal translocations and high hyperdiploidy, representing approximately 50% of all cases, 67 (25%) were P2RY8-CRLF2 positive. The respective clone sizes were ≥ 20% in 27% and < 20% in 73% of them. The cumulative incidence of relapse of the entire fusion-positive group was clone size independent and significantly higher than that of the fusion-negative group (35% ± 8% vs 13% ± 3%, P = .008) and primarily confined to the non–high-risk group. Of 22 P2RY8-CRLF2–positive diagnosis/relapse pairs, only 4/8 had the fusion-positive dominant clone conserved at relapse, whereas none of the original 14 fusion-positive small clones reappeared as the dominant relapse clone. We conclude that the majority of P2RY8-CRLF2–positive clones are small at diagnosis and virtually never generate a dominant relapse clone. Our findings therefore suggest that P2RY8-CRLF2–positive clones do not have the necessary proliferative or selective advantage to evolve into a disease-relevant relapse clone. PMID:23091296

Molecular and genetic characterization of the Ry adg locus on chromosome XI from Andigena potatoes conferring extreme resistance to potato virus Y.

PubMed

Herrera, María Del Rosario; Vidalon, Laura Jara; Montenegro, Juan D; Riccio, Cinzia; Guzman, Frank; Bartolini, Ida; Ghislain, Marc

2018-05-31

We have elucidated the Andigena origin of the potato Ry adg gene on chromosome XI of CIP breeding lines and developed two marker assays to facilitate its introgression in potato by marker-assisted selection. Potato virus Y (PVY) is causing yield and quality losses forcing farmers to renew periodically their seeds from clean stocks. Two loci for extreme resistance to PVY, one on chromosome XI and the other on XII, have been identified and used in breeding. The latter corresponds to a well-known source of resistance (Solanum stoloniferum), whereas the one on chromosome XI was reported from S. stoloniferum and S. tuberosum group Andigena as well. To elucidate its taxonomic origin in our breeding lines, we analyzed the nucleotide sequences of tightly linked markers (M45, M6) and screened 251 landraces of S. tuberosum group Andigena for the presence of this gene. Our results indicate that the PVY resistance allele on chromosome XI in our breeding lines originated from S. tuberosum group Andigena. We have developed two marker assays to accelerate the introgression of Ry adg gene into breeding lines by marker-assisted selection (MAS). First, we have multiplexed RYSC3, M6 and M45 DNA markers flanking the Ry adg gene and validated it on potato varieties with known presence/absence of the Ry adg gene and a progeny of 6,521 individuals. Secondly, we developed an allele-dosage assay particularly useful to identify multiplex Ry adg progenitors. The assay based on high-resolution melting analysis at the M6 marker confirmed Ry adg plex level as nulliplex, simplex and duplex progenitors and few triplex progenies. These marker assays have been validated and can be used to facilitate MAS in potato breeding.

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor.

PubMed

Bannister, Mark L; Alvarez-Laviada, Anita; Thomas, N Lowri; Mason, Sammy A; Coleman, Sharon; du Plessis, Christo L; Moran, Abbygail T; Neill-Hall, David; Osman, Hasnah; Bagley, Mark C; MacLeod, Kenneth T; George, Christopher H; Williams, Alan J

2016-08-01

Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels. We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca(2) (+) sparks in intact adult rat cardiac myocytes. Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca(2) (+) spark frequency. Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca(2) (+) sparks is likely, by analogy with flecainide, to result from Na(+) channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na(+) and RyR2 channels. © 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptor Function in Diabetes Mellitus

PubMed Central

Shao, Chun Hong; Tian, Chengju; Ouyang, Shouqiang; Moore, Caronda J.; Alomar, Fadhel; Nemet, Ina; D'Souza, Alicia; Nagai, Ryoji; Kutty, Shelby; Rozanski, George J.; Ramanadham, Sasanka; Singh, Jaipaul

2012-01-01

Heart failure and arrhythmias occur at 3 to 5 times higher rates among individuals with diabetes mellitus, compared with age-matched, healthy individuals. Studies attribute these defects in part to alterations in the function of cardiac type 2 ryanodine receptors (RyR2s), the principal Ca2+-release channels on the internal sarcoplasmic reticulum (SR). To date, mechanisms underlying RyR2 dysregulation in diabetes remain poorly defined. A rat model of type 1 diabetes, in combination with echocardiography, in vivo and ex vivo hemodynamic studies, confocal microscopy, Western blotting, mass spectrometry, site-directed mutagenesis, and [3H]ryanodine binding, lipid bilayer, and transfection assays, was used to determine whether post-translational modification by reactive carbonyl species (RCS) represented a contributing cause. After 8 weeks of diabetes, spontaneous Ca2+ release in ventricular myocytes increased ∼5-fold. Evoked Ca2+ release from the SR was nonuniform (dyssynchronous). Total RyR2 protein levels remained unchanged, but the ability to bind the Ca2+-dependent ligand [3H]ryanodine was significantly reduced. Western blotting and mass spectrometry revealed RCS adducts on select basic residues. Mutation of residues to delineate the physiochemical impact of carbonylation yielded channels with enhanced or reduced cytoplasmic Ca2+ responsiveness. The prototype RCS methylglyoxal increased and then decreased the RyR2 open probability. Methylglyoxal also increased spontaneous Ca2+ release and induced Ca2+ waves in healthy myocytes. Treatment of diabetic rats with RCS scavengers normalized spontaneous and evoked Ca2+ release from the SR, reduced carbonylation of RyR2s, and increased binding of [3H]ryanodine to RyR2s. From these data, we conclude that post-translational modification by RCS contributes to the heterogeneity in RyR2 activity that is seen in experimental diabetes. PMID:22648972

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

PubMed Central

Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Recombinant expression of Intrepicalcin from the scorpion Vaejovis intrepidus and its effect on skeletal ryanodine receptors.

PubMed

Vargas-Jaimes, Leonel; Xiao, Liang; Zhang, Jing; Possani, Lourival D; Valdivia, Héctor H; Quintero-Hernández, Verónica

2017-04-01

Scorpion venoms contain toxins that modulate ionic channels, among which are the calcins, a small group of short, basic peptides with an Inhibitor Cystine Knot (ICK) motif that target calcium release channels/ryanodine receptors (RyRs) with high affinity and selectivity. Here we describe the heterologous expression of Intrepicalcin, identified by transcriptomic analysis of venomous glands from Vaejovis intrepidus. Recombinant Intrepicalcin was obtained in Escherichia coli BL21-DE3 (periplasm) by fusing the Intrepicalcin gene to sequences coding for signal-peptide, thioredoxin, His-tag and enterokinase cleavage site. [ 3 H]Ryanodine binding, used as a functional index of RyR activity, revealed that recombinant Intrepicalcin activates skeletal RyR (RyR1) dose-dependently with K d =17.4±4.0nM. Intrepicalcin significantly augments the bell-shaped [Ca 2+ ]-[ 3 H]ryanodine binding curve at all [Ca 2+ ] ranges, as is characteristic of the calcins. In single channel recordings, Intrepicalcin induces the appearance of a subconductance state in RyR1 with a fractional value ∼55% of the full conductance state, very close to that of Vejocalcin. Furthermore, Intrepicalcin stimulates Ca 2+ release at an initial dose=45.3±2.5nM, and depletes ~50% of Ca 2+ load from skeletal sarcoplasmic reticulum vesicles. We conclude that active recombinant Intrepicalcin was successfully obtained without the need of manual oxidation, enabling it to target RyR1s with high affinity. This is the first calcin heterologously expressed in the periplasma of Escherichia coli BL21-DE3, shown to be pharmacologically effective, thus paving the way for the generation of Intrepicalcin variants that are required for structure-function relationship studies of calcins and RyRs. Copyright © 2017 Elsevier B.V. All rights reserved.

Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations.

PubMed

Chugun, Akihito; Sato, Osamu; Takeshima, Hiroshi; Ogawa, Yasuo

2007-01-01

To clarify whether activity of the ryanodine receptor type 2 (RyR2) is reduced in the sarcoplasmic reticulum (SR) of cardiac muscle, as is the case with the ryanodine receptor type 1 (RyR1), Ca(2+)-dependent [(3)H]ryanodine binding, a biochemical measure of Ca(2+)-induced Ca(2+) release (CICR), was determined using SR vesicle fractions isolated from rabbit and rat cardiac muscles. In the absence of an adenine nucleotide or caffeine, the rat SR showed a complicated Ca(2+) dependence, instead of the well-documented biphasic dependence of the rabbit SR. In the rat SR, [(3)H]ryanodine binding initially increased as [Ca(2+)] increased, with a plateau in the range of 10-100 microM Ca(2+), and thereafter further increased to an apparent peak around 1 mM Ca(2+), followed by a decrease. In the presence of these modulators, this complicated dependence prevailed, irrespective of the source. Addition of 0.3-1 mM Mg(2+) unexpectedly increased the binding two- to threefold and enhanced the affinity for [(3)H]ryanodine at 10-100 microM Ca(2+), resulting in the well-known biphasic dependence. In other words, the partial suppression of RyR2 is relieved by Mg(2+). Ca(2+) could be a substitute for Mg(2+). Mg(2+) also amplifies the responses of RyR2 to inhibitory and stimulatory modulators. This stimulating effect of Mg(2+) on RyR2 is entirely new, and is referred to as the third effect, in addition to the well-known dual inhibitory effects. This effect is critical to describe the role of RyR2 in excitation-contraction coupling of cardiac muscle, in view of the intracellular Mg(2+) concentration.

Pruning The ELM Survey: Characterizing Candidate Low-mass White Dwarfs through Photometric Variability

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

Bell, Keaton J.; Winget, D. E.; Montgomery, M. H.

We assess the photometric variability of nine stars with spectroscopic T {sub eff} and log g values from the ELM Survey that locates them near the empirical extremely low-mass (ELM) white dwarf instability strip. We discover three new pulsating stars: SDSS J135512.34+195645.4, SDSS J173521.69+213440.6, and SDSS J213907.42+222708.9. However, these are among the few ELM Survey objects that do not show radial velocity (RV) variations that confirm the binary nature expected of helium-core white dwarfs. The dominant 4.31 hr pulsation in SDSS J135512.34+195645.4 far exceeds the theoretical cut-off for surface reflection in a white dwarf, and this target is likely amore » high-amplitude δ Scuti pulsator with an overestimated surface gravity. We estimate the probability to be less than 0.0008 that the lack of measured RV variations in four of eight other pulsating candidate ELM white dwarfs could be due to low orbital inclination. Two other targets exhibit variability as photometric binaries. Partial coverage of the 19.342 hr orbit of WD J030818.19+514011.5 reveals deep eclipses that imply a primary radius >0.4 R {sub ⊙}—too large to be consistent with an ELM white dwarf. The only object for which our time series photometry adds support to ELM white dwarf classification is SDSS J105435.78−212155.9, which has consistent signatures of Doppler beaming and ellipsoidal variations. We conclude that the ELM Survey contains multiple false positives from another stellar population at T {sub eff}≲9000 K, possibly related to the sdA stars recently reported from SDSS spectra.« less

Pruning The ELM Survey: Characterizing Candidate Low-mass White Dwarfs through Photometric Variability

NASA Astrophysics Data System (ADS)

Bell, Keaton J.; Gianninas, A.; Hermes, J. J.; Winget, D. E.; Kilic, Mukremin; Montgomery, M. H.; Castanheira, B. G.; Vanderbosch, Z.; Winget, K. I.; Brown, Warren R.

2017-02-01

We assess the photometric variability of nine stars with spectroscopic Teff and log g values from the ELM Survey that locates them near the empirical extremely low-mass (ELM) white dwarf instability strip. We discover three new pulsating stars: SDSS J135512.34+195645.4, SDSS J173521.69+213440.6, and SDSS J213907.42+222708.9. However, these are among the few ELM Survey objects that do not show radial velocity (RV) variations that confirm the binary nature expected of helium-core white dwarfs. The dominant 4.31 hr pulsation in SDSS J135512.34+195645.4 far exceeds the theoretical cut-off for surface reflection in a white dwarf, and this target is likely a high-amplitude δ Scuti pulsator with an overestimated surface gravity. We estimate the probability to be less than 0.0008 that the lack of measured RV variations in four of eight other pulsating candidate ELM white dwarfs could be due to low orbital inclination. Two other targets exhibit variability as photometric binaries. Partial coverage of the 19.342 hr orbit of WD J030818.19+514011.5 reveals deep eclipses that imply a primary radius >0.4 R⊙—too large to be consistent with an ELM white dwarf. The only object for which our time series photometry adds support to ELM white dwarf classification is SDSS J105435.78-212155.9, which has consistent signatures of Doppler beaming and ellipsoidal variations. We conclude that the ELM Survey contains multiple false positives from another stellar population at Teff ≲ 9000 K, possibly related to the sdA stars recently reported from SDSS spectra.

Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells.

PubMed Central

Leite, M F; Dranoff, J A; Gao, L; Nathanson, M H

1999-01-01

The ryanodine receptor (RyR) is the principal Ca2+-release channel in excitable cells, whereas the inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) is primarily responsible for Ca2+ release in non-excitable cells, including epithelia. RyR also is expressed in a number of non-excitable cell types, but is thought to serve as an auxiliary or alternative Ca2+-release pathway in those cells. Here we use reverse transcription PCR to show that a polarized epithelium, the pancreatic acinar cell, expresses the type 2, but not the type 1 or 3, isoform of RyR. We furthermore use immunochemistry to demonstrate that the type 2 RyR is distributed throughout the basolateral and, to a lesser extent, the apical region of the acinar cell, but is excluded from the trigger zone, where cytosolic Ca2+ signals originate in this cell type. Since propagation of Ca2+ waves in acinar cells is sensitive to ryanodine, caffeine and Ca2+, these findings suggest that Ca2+ waves in this cell type result from the co-ordinated release of Ca2+, first from InsP3Rs in the trigger zone, then from RyRs elsewhere in the cell. RyR may play a fundamental role in Ca2+ signalling in polarized epithelia, including for Ca2+ signals initiated by InsP3. PMID:9882629

Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules.

PubMed

Romi, Fredrik; Bø, Lars; Skeie, Geir Olve; Myking, Andreas; Aarli, Johan A; Gilhus, Nils Erik

2002-07-01

Cortical-type thymomas are associated with myasthenia gravis (MG) in 50% of the cases. MG is caused by antibodies against the acetylcholine receptors (AChR), but additional non-AChR muscle autoantibodies such as those against titin and ryanodine receptor (RyR) are found in up to 95% of MG patients with thymoma. To elucidate the induction of non-AChR autoantibodies in thymoma-associated MG, we studied cortical-type thymomas from seven thymoma MG patients, and sera from six of them. All six had titin antibodies, and four had RyR antibodies. Titin and RyR epitopes were co-expressed along with LFA3 and B7 (BB1) costimulatory molecules on thymoma antigen-presenting cells (APC) in all thymomas. In normal thymus, the staining by anti-titin, anti-RyR, anti-LFA3, and anti-BB1 antibodies was weak and occurred exclusively in the medulla and perivascularly. Our results indicate a primary autosensitization against titin and RyR antigens inside the thymoma. In MG-associated thymoma, the mechanisms involved in the initial autosensitization against titin and RyR are probably similar to those implicated in the autosensitization against AChR. In all cases, there is an overexpression of muscle-like epitopes and costimulatory molecules indicating that the T-cell autoimmunization is actively promoted by the pathogenic microenvironment inside the thymoma.

RY-Coding and Non-Homogeneous Models Can Ameliorate the Maximum-Likelihood Inferences From Nucleotide Sequence Data with Parallel Compositional Heterogeneity.

PubMed

Ishikawa, Sohta A; Inagaki, Yuji; Hashimoto, Tetsuo

2012-01-01

In phylogenetic analyses of nucleotide sequences, 'homogeneous' substitution models, which assume the stationarity of base composition across a tree, are widely used, albeit individual sequences may bear distinctive base frequencies. In the worst-case scenario, a homogeneous model-based analysis can yield an artifactual union of two distantly related sequences that achieved similar base frequencies in parallel. Such potential difficulty can be countered by two approaches, 'RY-coding' and 'non-homogeneous' models. The former approach converts four bases into purine and pyrimidine to normalize base frequencies across a tree, while the heterogeneity in base frequency is explicitly incorporated in the latter approach. The two approaches have been applied to real-world sequence data; however, their basic properties have not been fully examined by pioneering simulation studies. Here, we assessed the performances of the maximum-likelihood analyses incorporating RY-coding and a non-homogeneous model (RY-coding and non-homogeneous analyses) on simulated data with parallel convergence to similar base composition. Both RY-coding and non-homogeneous analyses showed superior performances compared with homogeneous model-based analyses. Curiously, the performance of RY-coding analysis appeared to be significantly affected by a setting of the substitution process for sequence simulation relative to that of non-homogeneous analysis. The performance of a non-homogeneous analysis was also validated by analyzing a real-world sequence data set with significant base heterogeneity.

Electron-conformational transformations govern the temperature dependence of the cardiac ryanodine receptor gating

NASA Astrophysics Data System (ADS)

Moskvin, A. S.; Iaparov, B. I.; Ryvkin, A. M.; Solovyova, O. E.; Markhasin, V. S.

2015-07-01

Temperature influences many aspects of cardiac excitation-contraction coupling, in particular, hypothermia increases the open probability ( P open) of cardiac sarcoplasmic reticulum (SR) Ca2+-release channels (ryanodine-sensitive RyR channels) rising the SR Ca2+ load in mammalian myocytes. However, to the best of our knowledge, no theoretical models are available for that effect. Traditional Markov chain models do not provide a reasonable molecular mechanistic insight on the origin of the temperature effects. Here in the paper we address a simple physically clear electron-conformational model to describe the RyR gating and argue that a synergetic effect of external thermal fluctuation forces (Gaussian-Markovian noise) and internal friction via the temperature stimulation/suppression of the open-close RyR tunneling probability can be considered as a main contributor to temperature effects on the RyR gating. Results of the computer modeling allowed us to successfully reproduce all the temperature effects observed for an isolated RyR gating in vitro under reducing the temperature: increase in P open and mean open time without any significant effect on mean closed

Revision of the Oriental genus Holophris Mocsáry, 1890 and description of the genus Leptopareia Rosa & Xu, gen. nov. (Hymenoptera, Chrysididae).

PubMed

Rosa, Paolo; Wei, Na-Sen; Notton, David; Xu, Zai-Fu

2016-02-19

Two Oriental genera of the tribe Elampini (Chrysidinae) are here discussed. The genus Holophris Mocsáry, 1890 is redescribed, and the genus Leptopareia Rosa & Xu, gen. nov. (type species Hedychrum borneanum Cameron, 1908) is established. Two new species are described: Holophris thailandica Rosa, Wei, Notton & Xu, sp. nov. (Thailand), and Leptopareia luzonensis Rosa, Wei, Notton & Xu, sp. nov. (Philippines, Luzon). The lectotype of Hedychrum borneanum Cameron, 1908 is designated. New combinations are proposed for L. borneana (Cameron, 1908), comb. nov., L. purpurea (Smith, 1860), comb. nov., L. abyssinica (Mocsáry, 1914), comb. nov., L. confusa (Kimsey, 1988), comb. nov., L. congoensis (du Buysson, 1900), comb. nov., and L. kalliopsis (Zimmermann, 1961), comb. nov. (all are from Holophris Mocsáry). Holophris marginella (Mocsáry, 1890) is newly recorded from China and Thailand; H. taiwana (Tsuneki, 1970) from India, Indonesia and Laos; and Leptopareia borneana (Cameron, 1908) from Thailand. Keys to Oriental genera of the tribe Elampini and to Oriental species of the two genera are provided.

Oxidative Capacity and Fatigability in Run Trained Malignant Hyperthermia Susceptible Mice

PubMed Central

Rouviere, Clement; Corona, Benjamin T.; Ingalls, Christopher P.

2011-01-01

Introduction The purpose of this study was to test the hypothesis that Malignant Hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training. Methods Following 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS). Results Although RyR1Y522S/wt mice ran without experiencing MH episodes, they ran 42% less distance than wild type (WT) mice. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice. Discussion RyR1Y522S/wt mice can run without experiencing rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance. PMID:22431093

Oxidative capacity and fatigability in run-trained malignant hyperthermia-susceptible mice.

PubMed

Rouviere, Clement; Corona, Benjamin T; Ingalls, Christopher P

2012-04-01

The purpose of this study was to test the hypothesis that malignant hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training. After 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS). Although RyR1Y522S/wt mice ran without undergoing MH episodes, they ran 42% less distance than wild-type (WT) mice. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice. RyR1Y522S/wt mice can run without having rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance. Copyright © 2012 Wiley Periodicals, Inc.

Conformational Dynamics inside Amino-Terminal Disease Hotspot of Ryanodine Receptor

PubMed Central

Zhong, Xiaowei; Liu, Ying; Zhu, Li; Meng, Xing; Wang, Ruiwu; Van Petegem, Filip; Wagenknecht, Terence; Wayne Chen, S. R.; Liu, Zheng

2013-01-01

Summary The N-terminal region of both skeletal and cardiac ryanodine receptor is a disease mutation hotspot. Recently, a crystal structure of the RyR1 fragment (residues 1-559) was solved. This N-terminal structure contains three separate domains, A, B, and C, and was docked into a central vestibule in a full-length RyR1 cryo-EM map. Here we reconstructed 3D cryo-EM structures of two GFP-tagged RyR2s with GFP inserted after residue Glu-310 and Ser-437, respectively. The structures of RyR2E310-GFP and RyR2S437-GFP displayed an extra mass on domain B and C, directly validating the predicted docking model. Next, we revealed domain movements in molecular dynamics flexible fitting models in both the closed and open state cryo-EM maps. To further probe the conformational changes, we generated FRET pairs by inserting CFP or YFP in two selected domains, FRET studies of three dual-insertion pairs and three co-expressed single-insertion pairs showed the dynamic structural changes within the N-terminal domains. PMID:24139989

Putting out the fire: what terminates calcium-induced calcium release in cardiac muscle?

PubMed

Stern, Michael D; Cheng, Heping

2004-06-01

The majority of contractile calcium in cardiac muscle is released from stores in the sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR) through ryanodine receptors. Because CICR is intrinsically self-reinforcing, the stability of and graded regulation of cardiac EC coupling appear paradoxical. It is now well established that this gradation results from the stochastic recruitment of varying numbers of elementary local release events, which may themselves be regenerative, and which can be directly observed as calcium sparks. Ryanodine receptors (RyRs) are clustered in dense lattices, and most calcium sparks are now believed to involve activation of multiple RyRs. This implies that local CICR is regenerative, requiring a mechanism to terminate it. It was initially assumed that this mechanism was inactivation of the RyR, but during the decade since the discovery of sparks, no sufficiently strong inactivation mechanism has been demonstrated in vitro and all empirically determined gating schemes for the RyR give unstable EC coupling in Monte Carlo simulations. We consider here possible release termination mechanisms. Stochastic attrition is the spontaneous decay of active clusters due to random channel closure; calculations show that it is much too slow unless assisted by another process. Calcium-dependent RyR inactivation involving third-party proteins remains a viable but speculative mechanism; current candidates include calmodulin and sorcin. Local depletion of SR release terminal calcium could terminate release, however calculations and measurements leave it uncertain whether a sufficient diffusion resistance exists within the SR to sustain such depletion. Depletion could be assisted by dependence of RyR activity on SR lumenal [Ca(2+)]. There is substantial evidence for such lumenal activation, but it is not clear if it is a strong enough effect to account for the robust termination of sparks. The existence of direct interactions among clustered RyRs might account for the discrepancy between the inactivation properties of isolated RyRs and intact clusters. Such coupled gating remains controversial. Determining the mechanism of release termination is the outstanding unsolved problem of cardiac EC coupling, and will probably require extensive genetic manipulation of the EC coupling apparatus in its native environment to unravel the solution.

MicroRNA-1 and -133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex

PubMed Central

Belevych, Andriy E.; Sansom, Sarah E.; Terentyeva, Radmila; Ho, Hsiang-Ting; Nishijima, Yoshinori; Martin, Mickey M.; Jindal, Hitesh K.; Rochira, Jennifer A.; Kunitomo, Yukiko; Abdellatif, Maha; Carnes, Cynthia A.; Elton, Terry S.; Györke, Sandor; Terentyev, Dmitry

2011-01-01

In heart failure (HF), arrhythmogenic spontaneous sarcoplasmic reticulum (SR) Ca2+ release and afterdepolarizations in cardiac myocytes have been linked to abnormally high activity of ryanodine receptors (RyR2s) associated with enhanced phosphorylation of the channel. However, the specific molecular mechanisms underlying RyR2 hyperphosphorylation in HF remain poorly understood. The objective of the current study was to test the hypothesis that the enhanced expression of muscle-specific microRNAs (miRNAs) underlies the HF-related alterations in RyR2 phosphorylation in ventricular myocytes by targeting phosphatase activity localized to the RyR2. We studied hearts isolated from canines with chronic HF exhibiting increased left ventricular (LV) dimensions and decreased LV contractility. qRT-PCR revealed that the levels of miR-1 and miR-133, the most abundant muscle-specific miRNAs, were significantly increased in HF myocytes compared with controls (2- and 1.6-fold, respectively). Western blot analyses demonstrated that expression levels of the protein phosphatase 2A (PP2A) catalytic and regulatory subunits, which are putative targets of miR-133 and miR-1, were decreased in HF cells. PP2A catalytic subunit mRNAs were validated as targets of miR-133 by using luciferase reporter assays. Pharmacological inhibition of phosphatase activity increased the frequency of diastolic Ca2+ waves and afterdepolarizations in control myocytes. The decreased PP2A activity observed in HF was accompanied by enhanced Ca2+/calmodulin-dependent protein kinase (CaMKII)-mediated phosphorylation of RyR2 at sites Ser-2814 and Ser-2030 and increased frequency of diastolic Ca2+ waves and afterdepolarizations in HF myocytes compared with controls. In HF myocytes, CaMKII inhibitory peptide normalized the frequency of pro-arrhythmic spontaneous diastolic Ca2+ waves. These findings suggest that altered levels of major muscle-specific miRNAs contribute to abnormal RyR2 function in HF by depressing phosphatase activity localized to the channel, which in turn, leads to the excessive phosphorylation of RyR2s, abnormal Ca2+ cycling, and increased propensity to arrhythmogenesis. PMID:22163007

Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization.

PubMed

Beavers, David L; Wang, Wei; Ather, Sameer; Voigt, Niels; Garbino, Alejandro; Dixit, Sayali S; Landstrom, Andrew P; Li, Na; Wang, Qiongling; Olivotto, Iacopo; Dobrev, Dobromir; Ackerman, Michael J; Wehrens, Xander H T

2013-11-19

This study sought to study the role of junctophilin-2 (JPH2) in atrial fibrillation (AF). JPH2 is believed to have an important role in sarcoplasmic reticulum (SR) Ca(2+) handling and modulation of ryanodine receptor Ca(2+) channels (RyR2). Whereas defective RyR2-mediated Ca(2+) release contributes to the pathogenesis of AF, nothing is known about the potential role of JPH2 in atrial arrhythmias. Screening 203 unrelated hypertrophic cardiomyopathy patients uncovered a novel JPH2 missense mutation (E169K) in 2 patients with juvenile-onset paroxysmal AF (pAF). Pseudoknock-in (PKI) mouse models were generated to determine the molecular defects underlying the development of AF caused by this JPH2 mutation. PKI mice expressing E169K mutant JPH2 exhibited a higher incidence of inducible AF than wild type (WT)-PKI mice, whereas A399S-PKI mice expressing a hypertrophic cardiomyopathy-linked JPH2 mutation not associated with atrial arrhythmias were not significantly different from WT-PKI. E169K-PKI but not A399A-PKI atrial cardiomyocytes showed an increased incidence of abnormal SR Ca(2+) release events. These changes were attributed to reduced binding of E169K-JPH2 to RyR2. Atrial JPH2 levels in WT-JPH2 transgenic, nontransgenic, and JPH2 knockdown mice correlated negatively with the incidence of pacing-induced AF. Ca(2+) spark frequency in atrial myocytes and the open probability of single RyR2 channels from JPH2 knockdown mice was significantly reduced by a small JPH2-mimicking oligopeptide. Moreover, patients with pAF had reduced atrial JPH2 levels per RyR2 channel compared to sinus rhythm patients and an increased frequency of spontaneous Ca(2+) release events. Our data suggest a novel mechanism by which reduced JPH2-mediated stabilization of RyR2 due to loss-of-function mutation or reduced JPH2/RyR2 ratios can promote SR Ca(2+) leak and atrial arrhythmias, representing a potential novel therapeutic target for AF. Copyright © 2013. Published by Elsevier Inc.

Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization

PubMed Central

Voigt, Niels; Garbino, Alejandro; Dixit, Sayali S.; Landstrom, Andrew P.; Li, Na; Wang, Qiongling; Olivotto, Iacopo; Dobrev, Dobromir; Ackerman, Michael J.; Wehrens, Xander H.T.

2013-01-01

Objectives To study the role of junctophilin 2 (JPH2) in atrial fibrillation (AF). Background JPH2 is believed to have an important role in sarcoplasmic reticulum (SR) Ca2+ handling and modulation of ryanodine receptor Ca2+ channels (RyR2). Whereas defective RyR2-mediated Ca2+ release contributes to the pathogenesis of AF, nothing is known about the potential role of JPH2 in atrial arrhythmias. Methods Screening 203 unrelated hypertrophic cardiomyopathy patients uncovered a novel JPH2 missense mutation (E169K) in 2 patients with juvenile-onset paroxysmal AF (pAF). Pseudo-knockin (PKI) mouse models were generated to determine the molecular defects underlying the development of AF caused by this JPH2 mutation. Results PKI mice expressing E169K mutant JPH2 exhibited a higher incidence of inducible AF compared with wildtype (WT)-PKI mice, while A399S-PKI mice expressing a HCM-linked JPH2 mutation not associated with atrial arrhythmias were not significantly different from WT-PKI. E169K-PKI but not A399A-PKI atrial cardiomyocytes showed an increased incidence of abnormal SR Ca2+ release events. These changes were attributed to reduced binding of E169KJPH2 to RyR2. Atrial JPH2 levels in WT-JPH2 transgenic, nontransgenic, and JPH2 knockdown mice correlated negatively with the incidence of pacing-induced AF. Ca2+ spark frequency in atrial myocytes and the open probability of single RyR2 channels from JPH2 knockdown mice was significantly reduced by a small JPH2-mimicking oligopeptide. Moreover, patients with pAF had reduced atrial JPH2 levels per RyR2 channel compared to sinus rhythm patients, and an increased frequency of spontaneous Ca2+ release events. Conclusions Our data suggest a novel mechanism by which reduced JPH2-mediated stabilization of RyR2 due to loss-of-function mutation or reduced JPH2:RyR2 ratios can promote SR Ca2+ leak and atrial arrhythmias, representing a potential novel therapeutic target for AF. PMID:23973696

REACTIVE CARBONYL SPECIES AND THEIR ROLES IN SARCOPLASMIC RETICULUM Ca2+ CYCLING DEFECT IN THE DIABETIC HEART

PubMed Central

Tian, Chengju; Alomar, Fadhel; Moore, Caronda J; Shao, Chun Hong; Kutty, Shelby; Singh, Jaipaul; Bidasee, Keshore R.

2016-01-01

Efficient and rhythmic cardiac contractions depend critically on the adequate and synchronized release of Ca2+ from the sarcoplasmic reticulum (SR) via ryanodine receptor Ca2+ release channels (RyR2) and its reuptake via sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a). It is well established that this orchestrated process becomes compromised in diabetes. What remain incompletely defined are the molecular mechanisms responsible for the dysregulation of RyR2 and SERCA2a in diabetes. Earlier, found elevated levels of carbonyl adducts on RyR2 and SERCA2a isolated from hearts of type 1 diabetic rats and showed the presence of these post-translational modifications compromised their functions. We also showed that these mono- and di-carbonyl reactive carbonyl species (RCS) do not indiscriminately react with all basic amino acid residues on RyR2 and SERCA2a; some residues are more susceptible to carbonylation (modification by RCS) than others. A key unresolved question in the field is which of the many RCS that are upregulated in the heart in diabetes chemically react with RyR2 and SERCA2a? This brief review introduces readers to the field of RCS and their roles in perturbing SR Ca2+ cycling in diabetes. It also provides new experimental evidence that not all RCS that are upregulated in the heart in diabetes chemically react with RyR2 and SERCA2a, methylglyoxal and glyoxal preferentially do. PMID:23430128

Rare earth element-enriched yeast improved egg production and egg quality in laying hens in the late period of peak egg production.

PubMed

Cai, L; Nyachoti, C M; Hancock, J D; Lee, J Y; Kim, Y H; Lee, D H; Kim, I H

2016-06-01

The objective of this study was to determine the effects of rare earth element-enriched yeast (RY) on egg production, coefficient of total tract apparent digestibility (CTTAD), egg quality, excreta gas emission and excreta microbiota of laying hens. A total of 216 ISA brown laying hens of 52 weeks of age were used in a 5-week feeding trial and data were collected every week. Birds were randomly allotted to three dietary treatments each with six replicates and 12 hens per replicate. Each cage (38 cm width × 50 cm length × 40 cm height) contained one hen. Treatments consisted of corn-soya bean meal-based diet supplemented with 0, 500 or 1000 mg/kg of RY. From weeks 55 to 56, inclusion of RY linearly increased (p < 0.05) egg production. The CTTAD of nitrogen was increased (linear, p < 0.05) with increasing dietary level of RY. In week 55, yolk height and Haugh units were increased linearly (p < 0.05) with increasing dietary RY content. However, no significant effects were observed in terms of excreta emissions and excreta microbiota in laying hens. In conclusion, dietary supplementation with RY improved egg production and CTTAD of nitrogen and slightly improved egg quality in laying hens of the late period of peak egg production. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Long-Term Simulated Microgravity Causes Cardiac RyR2 Phosphorylation and Arrhythmias in Mice

PubMed Central

Respress, Jonathan L.; Gershovich, Pavel M.; Wang, Tiannan; Reynolds, Julia O.; Skapura, Darlene G.; Sutton, Jeffrey P.; Miyake, Christina Y.; Wehrens, Xander H.T.

2014-01-01

Background Long-term exposure to microgravity during space flight may lead to cardiac remodeling and rhythm disturbances. In mice, hindlimb unloading (HU) mimics the effects of microgravity and stimulates physiological adaptations, including cardiovascular deconditioning. Recent studies have demonstrated an important role played by changes in intracellular Ca handling in the pathogenesis of heart failure and arrhythmia. In this study, we tested the hypothesis that cardiac remodeling following HU in mice involves abnormal intracellular Ca regulation through the cardiac ryanodine receptor (RyR2). Methods and Results Mice were subjected to HU by tail suspension for 28 to 56 days in order to induce cardiac remodeling (n=15). Control mice (n=19) were treated equally, with the exception of tail suspension. Echocardiography revealed cardiac enlargement and depressed contractility starting at 28 days post-HU versus control. Moreover, mice were more susceptible to pacing-induced ventricular arrhythmias after HU. Ventricular myocytes isolated from HU mice exhibited an increased frequency of spontaneous sarcoplasmic reticulum (SR) Ca release events and enhanced SR Ca leak via RyR2. Western blotting revealed increased RyR2 phosphorylation at S2814, and increased CaMKII auto-phosphorylation at T287, suggesting that CaMKII activation of RyR2 might underlie enhanced SR Ca release in HU mice. Conclusion These data suggest that abnormal intracellular Ca handling, likely due to increased CaMKII phosphorylation of RyR2, plays a role in cardiac remodeling following simulated microgravity in mice. PMID:25227892

Excess TGF-β mediates muscle weakness associated with bone metastases in mice

PubMed Central

Reiken, Steven; Xie, Wenjun; Andersson, Daniel C.; John, Sutha; Chiechi, Antonella; Wright, Laura E.; Umanskaya, Alisa; Niewolna, Maria; Trivedi, Trupti; Charkhzarrin, Sahba; Khatiwada, Pooja; Wronska, Anetta; Haynes, Ashley; Benassi, Maria Serena; Witzmann, Frank A.; Zhen, Gehua; Wang, Xiao; Cao, Xu; Roodman, G. David; Marks, Andrew R.; Guise, Theresa A.

2015-01-01

Cancer-associated muscle weakness is poorly understood and there is no effective treatment. Here, we find that seven different mouse models of human osteolytic bone metastases, representing breast, lung and prostate cancers, as well as multiple myeloma exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that TGF-β, released from the bone surface as a result of metastasis-induced bone destruction upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor/calcium (Ca2+) release channel (RyR1). The oxidized RyR1 channels leaked Ca2+, resulting in lower intracellular signaling required for proper muscle contraction. We found that inhibiting RyR1 leak, TGF-β signaling, TGF-β release from bone or Nox4 all improved muscle function in mice with MDA-MB-231 bone metastases. Humans with breast cancer- or lung cancer-associated bone metastases also had oxidized skeletal muscle RyR1 that is not seen in normal muscle. Similarly, skeletal muscle weakness, higher levels of Nox4 protein and Nox4 binding to RyR1, and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a non-malignant metabolic bone disorder associated with increased TGF-β activity. Thus, metastasis-induced TGF-β release from bone contributes to muscle weakness by decreasing Ca2+-induced muscle force production. PMID:26457758

From contraction to gene expression: nanojunctions of the sarco/endoplasmic reticulum deliver site- and function-specific calcium signals.

PubMed

Evans, A Mark; Fameli, Nicola; Ogunbayo, Oluseye A; Duan, Jingxian; Navarro-Dorado, Jorge

2016-08-01

Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.

Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy.

PubMed

Alves, Mariana; Gomez-Villafuertes, Rosa; Delanty, Norman; Farrell, Michael A; O'Brien, Donncha F; Miras-Portugal, Maria Teresa; Hernandez, Miguel Diaz; Henshall, David C; Engel, Tobias

2017-09-01

ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy. Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death. Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry 2 , P2ry 4 , and P2ry 6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry 1 , P2ry 12 , P2ry 13 . Protein levels of P2Y 1 , P2Y 2 , P2Y 4 , and P2Y 6 were increased after status epilepticus, whereas P2Y 12 expression was decreased. In the chronic phase, P2ry 1 , P2ry 2 , and P2ry 6 transcription and P2Y 1 , P2Y 2 , and P2Y 12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y 1 and P2Y 2 protein expression was increased, whereas P2Y 13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice. The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Decreased production of higher alcohols by Saccharomyces cerevisiae for Chinese rice wine fermentation by deletion of Bat aminotransferases.

PubMed

Zhang, Cui-Ying; Qi, Ya-Nan; Ma, Hong-Xia; Li, Wei; Dai, Long-Hai; Xiao, Dong-Guang

2015-04-01

An appropriate level of higher alcohols produced by yeast during the fermentation is one of the most important factors influencing Chinese rice wine quality. In this study, BAT1 and BAT2 single- and double-gene-deletion mutant strains were constructed from an industrial yeast strain RY1 to decrease higher alcohols during Chinese rice wine fermentation. The results showed that the BAT2 single-gene-deletion mutant strain produced best improvement in the production of higher alcohols while remaining showed normal growth and fermentation characteristics. Furthermore, a BAT2 single-gene-deletion diploid engineered strain RY1-Δbat2 was constructed and produced low levels of isobutanol and isoamylol (isoamyl alcohol and active amyl alcohol) in simulated fermentation of Chinese rice wine, 92.40 and 303.31 mg/L, respectively, which were 33.00 and 14.20 % lower than those of the parental strain RY1. The differences in fermentation performance between RY1-Δbat2 and RY1 were minor. Therefore, construction of this yeast strain is important in future development in Chinese wine industry and provides insights on generating yeast strains for other fermented alcoholic beverages.

Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4

PubMed Central

Sun, Qi-An; Hess, Douglas T.; Nogueira, Leonardo; Yong, Sandro; Bowles, Dawn E.; Eu, Jerry; Laurita, Kenneth R.; Meissner, Gerhard; Stamler, Jonathan S.

2011-01-01

Physiological sensing of O2 tension (partial O2 pressure, pO2) plays an important role in some mammalian cellular systems, but striated muscle generally is not considered to be among them. Here we describe a molecular mechanism in skeletal muscle that acutely couples changes in pO2 to altered calcium release through the ryanodine receptor–Ca2+-release channel (RyR1). Reactive oxygen species are generated in proportion to pO2 by NADPH oxidase 4 (Nox4) in the sarcoplasmic reticulum, and the consequent oxidation of a small set of RyR1 cysteine thiols results in increased RyR1 activity and Ca2+ release in isolated sarcoplasmic reticulum and in cultured myofibers and enhanced contractility of intact muscle. Thus, Nox4 is an O2 sensor in skeletal muscle, and O2-coupled hydrogen peroxide production by Nox4 governs the redox state of regulatory RyR1 thiols and thereby governs muscle performance. These findings reveal a molecular mechanism for O2-based signaling by an NADPH oxidase and demonstrate a physiological role for oxidative modification of RyR1. PMID:21896730

Quasi-Periodic Long-Term Quadrature Light Variability in Early Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine Joan

2015-08-01

Four years of Kepler observations have revealed a class of Algol-type binaries in which the relative brightness of the quadrature light varies from > 1 to <1 on a time scale of about 100-400 days. The behavior pattern is quasi-periodic. We call these systems L/T (leading hemisphere/ trailing hemisphere) variables. Although L/T inequality in eclipsing binaries has been noted from ground-based photometry by several observers since the early 1950s, the regular or quasi-regular switching between maxima is new. Twenty L/T systems have so far been found in the Kepler database and at least three classes of L/T behavior have been identified. In this presentation I will give an update on the L/T phenomenon gleaned from the Kepler and K2 databases. The Kepler and K2 light curves are being analyzed with the 2015 version of the Wilson-Devinney (WD) program that includes major improvements in modeling star spots (i.e. spot motions due to drift and stellar rotation and spot growth and decay). The prototype L/T variable is WX Draconis (A8V + K0IV, P=1.80 d) which shows L/ T light variations of 2-3%. The primary is a delta Scuti star with a dominant pulsation period of 41 m. Preliminary analysis of the WX Dra data suggests that the L/T variability can be fit with either an accretion hot spot on the primary (T = 2.3 Tphot) that jumps in longitude or a magnetic cool spotted region on the secondary. If the latter model is correct the dark region must occupy at least 20% of the surface of the facing hemisphere of the secondary if it is completely black, or a larger area if not completely black. In both hot and cool spot scenarios magnetic fields must play a role in the activity. Support from NASA grants NNX11AC78G and NNX12AE44G and USC’s Women in Science and Engineering (WiSE) program is greatly appreciated.

Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor

PubMed Central

Uchinoumi, Hitoshi; Yano, Masafumi; Suetomi, Takeshi; Ono, Makoto; Xu, Xiaojuan; Tateishi, Hiroki; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Yamamoto, Takeshi; Ikeda, Yasuhiro; Ohkusa, Tomoko; Ikemoto, Noriaki; Matsuzaki, Masunori

2010-01-01

Rationale Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in a well-defined region of the cardiac type-2 ryanodine receptor (RyR2). However, the underlying mechanism by which a single mutation in such a large molecule produces drastic effects on channel function remains unresolved. Objective Using a knock-in (KI) mouse model with a human CPVT-associated RyR2 mutation (R2474S), we investigated the molecular mechanism by which CPVT is induced by a single point mutation within the RyR2. Methods and Results The R2474S/+ KI mice showed no apparent structural or histological abnormalities in the heart, but they showed clear indications of other abnormalities. Bidirectional or polymorphic VT was induced after exercise on a treadmill. The interaction between the N-terminal (aa 1–600) and central (aa 2000–2500) domains of the RyR2 (an intrinsic mechanism to close Ca2+ channels) was weakened (domain unzipping). Upon protein kinase A (PKA)-mediated phosphorylation of the RyR2, this domain unzipping further increased, resulting in a significant increase in the frequency of spontaneous Ca2+ transients. cAMP-induced aberrant Ca2+ release events (Ca2+ sparks/waves) occurred at much lower sarcoplasmic reticulum (SR) Ca2+ content as compared to the wild-type (WT). Addition of a domain-unzipping peptide, DPc10 (aa 2460–2495), to the WT reproduced the aforementioned abnormalities that are characteristic of the R2474S/+ KI mice. Addition of DPc10 to the (cAMP-treated) KI cardiomyocytes produced no further effect. Conclusions A single point mutation within the RyR2 sensitizes the channel to agonists and reduces the threshold of luminal [Ca2+] for activation, primarily mediated by defective inter-domain interaction within the RyR2. PMID:20224043

Clinical outcomes of Roux-en-Y and Billroth I reconstruction after a distal gastrectomy for gastric cancer: What is the optimal reconstructive procedure?

PubMed

Tanaka, Shinnosuke; Matsuo, Katsuichi; Matsumoto, Hisanobu; Maki, Takanobu; Nakano, Masahiko; Sasaki, Takamitsu; Yamashita, Yuichi

2011-01-01

The aim of this study was to evaluate the clinical advantages of Roux-en-Y (R-Y) and Billroth-I (B-I) reconstruction after distal gastrectomy for gastric cancer by examining the postoperative symptoms based on a patient questionnaire and patient nutrition. In addition, this study determined which of the R-Y or B-I procedures is preferable following distal gastrectomy. Fifty-one patients who had undergone R-Y reconstruction and 50 patients who had undergone B-I reconstruction were retrospectively enrolled in this study. The operative and postoperative findings such as operating time, blood loss, complications, and postoperative hospital stay were evaluated as short-term clinical outcomes. Postoperative serum nutrition parameters, transition of body weight, incidence of residual gastritis, and clinical symptoms were evaluated as mid-term clinical outcomes. An assessment of symptoms was based on a questionnaire concerning dumping symptoms, reflux symptoms, food intake, and satisfaction with the operation. No significant differences were observed in the operative and postoperative clinical parameters without stage grouping. The transition of serum nutrition parameters revealed no significant differences between the two groups for the preoperative and postoperative states. Dumping symptoms, reflux symptoms, and abdominal symptoms were less frequent in R-Y patients, but there were no significant differences between the two groups. Moreover, the differences in body weight recovery rates were not found to be statistically significant between two groups. However, the incidence of residual gastritis was significantly less in R-Y patients (21.2%) than in B-I patients (68.8%) (p < 0.05). The questionnaire results regarding food intake and surgery satisfaction were not significantly different between the two groups. Definite clinical advantages were not recognized in patients with R-Y reconstruction. B-I and R-Y reconstructive procedures should be selected according to the condition of each patient. However, the advantages of these reconstruction procedures following distal gastrectomy would only be revealed in large randomized controlled trials.

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

Hierarchical accumulation of RyR post-translational modifications drives disease progression in dystrophic cardiomyopathy.

PubMed

Kyrychenko, Sergii; Poláková, Eva; Kang, Chifei; Pocsai, Krisztina; Ullrich, Nina D; Niggli, Ernst; Shirokova, Natalia

2013-03-15

Duchenne muscular dystrophy (DMD) is a muscle disease with serious cardiac complications. Changes in Ca(2+) homeostasis and oxidative stress were recently associated with cardiac deterioration, but the cellular pathophysiological mechanisms remain elusive. We investigated whether the activity of ryanodine receptor (RyR) Ca(2+) release channels is affected, whether changes in function are cause or consequence and which post-translational modifications drive disease progression. Electrophysiological, imaging, and biochemical techniques were used to study RyRs in cardiomyocytes from mdx mice, an animal model of DMD. Young mdx mice show no changes in cardiac performance, but do so after ∼8 months. Nevertheless, myocytes from mdx pups exhibited exaggerated Ca(2+) responses to mechanical stress and 'hypersensitive' excitation-contraction coupling, hallmarks of increased RyR Ca(2+) sensitivity. Both were normalized by antioxidants, inhibitors of NAD(P)H oxidase and CaMKII, but not by NO synthases and PKA antagonists. Sarcoplasmic reticulum Ca(2+) load and leak were unchanged in young mdx mice. However, by the age of 4-5 months and in senescence, leak was increased and load was reduced, indicating disease progression. By this age, all pharmacological interventions listed above normalized Ca(2+) signals and corrected changes in ECC, Ca(2+) load, and leak. Our findings suggest that increased RyR Ca(2+) sensitivity precedes and presumably drives the progression of dystrophic cardiomyopathy, with oxidative stress initiating its development. RyR oxidation followed by phosphorylation, first by CaMKII and later by PKA, synergistically contributes to cardiac deterioration.

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

Garg, A

The SuperMACHO Project is a five-year survey toward the Large Magellanic Cloud (LMC) aimed at understanding the nature of the populations of lenses responsible for the excess microlensing rates observed by the MACHO project. Survey observations were completed in 2006. A rich side-product of this survey is a catalog of variable sources down to a depth of VR 23, including many classes of pulsating variables such as {delta}-Scuti and RR Lyrae. Through their position in the Period-Luminosity diagram and their light curve characteristics we have identified 2323 high amplitude {delta}-Scuti (HADS) having high quality light curves. sing Fourier decomposition ofmore » the HADS light curves, we find that the period-luminosity (PL) relation defined by the firt-overtone (FO) pulsators does not show a clear separation from the PL-relation defined by the fundamental (F) pulsators. This differs from other instability strip pulsators such as type c RR Lyrae. We also present evidence for a larger amplitude, subluminous population of HADS similar to that observed in Fornax.« less

The envelope of the power spectra of over a thousand δ Scuti stars. The T̅eff - νmax scaling relation

NASA Astrophysics Data System (ADS)

Barceló Forteza, S.; Roca Cortés, T.; García, R. A.

2018-06-01

CoRoT and Kepler high-precision photometric data allowed the detection and characterization of the oscillation parameters in stars other than the Sun. Moreover, thanks to the scaling relations, it is possible to estimate masses and radii for thousands of solar-type oscillating stars. Recently, a Δν - ρ relation has been found for δ Scuti stars. Now, analysing several hundreds of this kind of stars observed with CoRoT and Kepler, we present an empiric relation between their frequency at maximum power of their oscillation spectra and their effective temperature. Such a relation can be explained with the help of the κ-mechanism and the observed dispersion of the residuals is compatible with they being caused by the gravity-darkening effect. Table A.1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/614/A46

Engineering an Affinity-Enhanced Peptide through Optimization of Cyclization Chemistry.

PubMed

Ngambenjawong, Chayanon; Pineda, Julio Marco B; Pun, Suzie H

2016-12-21

Peptide cyclization is a strategy used to improve stability and activity of peptides. The most commonly used cyclization method is disulfide bridge formation of cysteine-containing peptides, as is typically found in nature. Over the years, an increasing number of alternative chemistries for peptide cyclization with improved efficiency, kinetics, orthogonality, and stability have been reported. However, there has been less appreciation for the opportunity to fine-tune peptide activity via the diverse chemical entities introduced at the site of linkage by different cyclization strategies. Here, we demonstrate how cyclization optimization of an M2 "anti-inflammatory" macrophage-binding peptide (M2pep) resulted in a significant increase in binding affinity of the optimized analog to M2 macrophages while maintaining binding selectivity compared to M1 "pro-inflammatory" macrophages. In this study, we report synthesis and evaluation of four cyclic M2pep(RY) analogs with diverse cyclization strategies: (1) Asp-[amide]-Lys, (2) azido-Lys-[triazole(copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC))]-propargyl-Gly, (3) Cys-[decafluorobiphenyl (DFBP)]-Cys, and (4) Cys-[decafluorobiphenyl sulfone (DFS)]-Cys, whereby the chemical entity or linker at the linkage site is shown in the square bracket and is between the residues involved in cyclization. These peptides are compared to a disulfide-cyclized M2pep(RY) that we previously reported as a serum-stable, affinity-enhanced analog to the original linear M2pep. DFBP-cyclized M2pep(RY) exhibits the highest binding activity to M2 macrophages with apparent dissociation constant (K D ) about 2.03 μM compared to 36.3 μM for the original disulfide-cyclized M2pep(RY) and 220 μM for the original linear peptide. DFS-cyclized M2pep(RY) also binds more strongly than the original cyclized analog, whereas amide- and triazole-cyclized M2pep(RY) analogs bind less strongly. We verified that DFBP alone has negligible binding to M2 macrophages and the incorporation of diphenylalanine to the original sequence improves binding activity at the expense of solubility and increased toxicity. In conclusion, we report development of cyclic M2pep(RY) analogs with diverse cyclization strategies leading to the discovery of DFBP-cyclized M2pep(RY) with enhanced M2 macrophage-binding activity.

Expression of a chitin deacetylase gene, up-regulated in Cryptococcus laurentii strain RY1, under nitrogen limitation.

PubMed

Chakraborty, Writachit; Sarkar, Soumyadev; Chakravorty, Somnath; Bhattacharya, Semantee; Bhattacharya, Debanjana; Gachhui, Ratan

2016-05-01

This study reports the identification of a chitin deacetylase gene in Cryptococcus laurentii strain RY1 over-expressing under nitrogen limitation by differential display. The up-regulation took place in robustly growing cells rather than in starving quiescent autophagic cells. Quantitative Real Time-PCR, enzyme activity in cell lysate and cell wall analysis corroborated the up-regulation of chitin deacetylase under nitrogen limitation. These results suggest chitin deacetylase might play a significant role in nitrogen limiting growth of Cryptococcus laurentii strain RY1. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution

PubMed Central

Wu, Jianping; Li, Zhangqiang; Xie, Tian; Peng, Wei; Yin, Changcheng; Li, Xueming; Scheres, Sjors H.W.; Shi, Yigong; Yan, Nieng

2014-01-01

The ryanodine receptors (RyRs) are high-conductance intracellular Ca2+ channels that play a pivotal role in the excitation-contraction coupling of skeletal and cardiac muscles. RyRs are the largest known ion channels, with a homotetrameric organization and approximately 5000 residues in each protomer. Here we report the structure of the rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 Å, determined by single-particle electron cryo-microscopy. Three previously uncharacterized domains, named Central, Handle, and Helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity filter vestibule. The four elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the Central domains and the channel domain. These structural features explain high ion conductance by RyRs and the long-range allosteric regulation of channel activities. PMID:25517095

Intracellular Calcium Release Channels Mediate Their Own Countercurrent: The Ryanodine Receptor Case Study

PubMed Central

Gillespie, Dirk; Fill, Michael

2008-01-01

Intracellular calcium release channels like ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs) mediate large Ca2+ release events from Ca2+ storage organelles lasting >5 ms. To have such long-lasting Ca2+ efflux, a countercurrent of other ions is necessary to prevent the membrane potential from becoming the Ca2+ Nernst potential in <1 ms. A recent model of ion permeation through a single, open RyR channel is used here to show that the vast majority of this countercurrent is conducted by the RyR itself. Consequently, changes in membrane potential are minimized locally and instantly, assuring maintenance of a Ca2+-driving force. This RyR autocountercurrent is possible because of the poor Ca2+ selectivity and high conductance for both monovalent and divalent cations of these channels. The model shows that, under physiological conditions, the autocountercurrent clamps the membrane potential near 0 mV within ∼150 μs. Consistent with experiments, the model shows how RyR unit Ca2+ current is defined by luminal [Ca2+], permeable ion composition and concentration, and pore selectivity and conductance. This very likely is true of the highly homologous pore of the IP3R channel. PMID:18621826

The Effect of Selenium Enrichment on Baker s Yeast Proteome

PubMed Central

El-Bayoumy, Karam; Das, Arunangshu; Russell, Stephen; Wolfe, Steven; Jordan, Rick; Renganathan, Kutralanathan; Loughran, Thomas P.; Somiari, Richard

2011-01-01

The use of regular yeast (RY) and selenium-enriched yeast (SEY) as dietary supplement is of interest because the Nutritional Prevention of Cancer (NPC) trial revealed that SEY but not RY decreased the incidence of prostate cancer (PC). Using two-dimensional difference in gel electrophoresis (2D-DIGE) – tandem mass spectrometry (MS/MS) approach, we performed proteomic analysis of RY and SEY to identify proteins that are differentially expressed as a result of selenium enrichment. 2D-DIGE revealed 96 candidate protein spots that were differentially expressed (p≤0.05) between SEY and RY. The 96 spots were selected, sequenced by LC/MS/MS and 37 proteins were unequivocally identified. The 37 identified proteins were verified with ProteinProphet software and mapped to existing Gene Ontology categories. Furthermore, the expression profile of 5 of the proteins with validated or putative roles in the carcinogenesis process, and for which antibodies against human forms of the proteins are available commercially were verified by western analysis. This study provides evidence for the first time that SEY contains higher levels of Pyruvate Kinase, HSP70, and Elongation factor 2 and lower levels of Eukaryotic Translation Initiation Factor 5A-2 and Triosephosphate Isomerase than those found in RY. PMID:22067702

Expression analysis of G Protein-Coupled Receptors in mouse macrophages.

PubMed

Lattin, Jane E; Schroder, Kate; Su, Andrew I; Walker, John R; Zhang, Jie; Wiltshire, Tim; Saijo, Kaoru; Glass, Christopher K; Hume, David A; Kellie, Stuart; Sweet, Matthew J

2008-04-29

Monocytes and macrophages express an extensive repertoire of G Protein-Coupled Receptors (GPCRs) that regulate inflammation and immunity. In this study we performed a systematic micro-array analysis of GPCR expression in primary mouse macrophages to identify family members that are either enriched in macrophages compared to a panel of other cell types, or are regulated by an inflammatory stimulus, the bacterial product lipopolysaccharide (LPS). Several members of the P2RY family had striking expression patterns in macrophages; P2ry6 mRNA was essentially expressed in a macrophage-specific fashion, whilst P2ry1 and P2ry5 mRNA levels were strongly down-regulated by LPS. Expression of several other GPCRs was either restricted to macrophages (e.g. Gpr84) or to both macrophages and neural tissues (e.g. P2ry12, Gpr85). The GPCR repertoire expressed by bone marrow-derived macrophages and thioglycollate-elicited peritoneal macrophages had some commonality, but there were also several GPCRs preferentially expressed by either cell population. The constitutive or regulated expression in macrophages of several GPCRs identified in this study has not previously been described. Future studies on such GPCRs and their agonists are likely to provide important insights into macrophage biology, as well as novel inflammatory pathways that could be future targets for drug discovery.

Purkinje cells from RyR2 mutant mice are highly arrhythmogenic but responsive to targeted therapy.

PubMed

Kang, Guoxin; Giovannone, Steven F; Liu, Nian; Liu, Fang-Yu; Zhang, Jie; Priori, Silvia G; Fishman, Glenn I

2010-08-20

The Purkinje fiber network has been proposed as the source of arrhythmogenic Ca(2+) release events in catecholaminergic polymorphic ventricular tachycardia (CPVT), yet evidence supporting this mechanism at the cellular level is lacking. We sought to determine the frequency and severity of spontaneous Ca(2+) release events and the response to the antiarrhythmic agent flecainide in Purkinje cells and ventricular myocytes from RyR2(R4496C/+) CPVT mutant mice and littermate controls. We crossed RyR2(R4496C/+) knock-in mice with the newly described Cntn2-EGFP BAC transgenic mice, which express a fluorescent reporter gene in cells of the cardiac conduction system, including the distal Purkinje fiber network. Isolated ventricular myocytes (EGFP(-)) and Purkinje cells (EGFP(+)) from wild-type hearts and mutant hearts were distinguished by epifluorescence and intracellular Ca(2+) dynamics recorded by microfluorimetry. Both wild-type and RyR2(R4496C/+) mutant Purkinje cells displayed significantly slower kinetics of activation and relaxation compared to ventricular myocytes of the same genotype, and tau(decay) in the mutant Purkinje cells was significantly slower than that observed in wild-type Purkinje cells. Of the 4 groups studied, RyR2(R4496C/+) mutant Purkinje cells were also most likely to develop spontaneous Ca(2+) release events, and the number of events per cell was also significantly greater. Furthermore, with isoproterenol treatment, although all 4 groups showed increases in the frequency of arrhythmogenic Ca(2+(i)) events, the RyR2(R4496C/+) Purkinje cells responded with the most profound abnormalities in intracellular Ca(2+) handling, including a significant increase in the frequency of unstimulated Ca(2+(i)) events and the development of alternans, as well as isolated and sustained runs of triggered beats. Both Purkinje cells and ventricular myocytes from wild-type mice showed suppression of spontaneous Ca(2+) release events with flecainide, whereas in RyR2(R4496C/+) mice, the Purkinje cells were preferentially responsive to drug. In contrast, the RyR2 blocker tetracaine was equally efficacious in mutant Purkinje cells and ventricular myocytes. Purkinje cells display a greater propensity to develop abnormalities in intracellular Ca(2+) handling than ventricular myocytes. This proarrhythmic behavior is enhanced by disease-causing mutations in the RyR2 Ca(2+) release channel and greatly exacerbated by catecholaminergic stimulation, with the development of arrhythmogenic triggered beats. These data support the concept that Purkinje cells are critical contributors to arrhythmic triggers in animal models and humans with CPVT and suggest a broader role for the Purkinje fiber network in the genesis of ventricular arrhythmias.

Searching for Extrasolar Trojan Planets: A Status Report

NASA Astrophysics Data System (ADS)

Caton, D. B.; Davis, S. A.; Kluttz, K. A.; Stamilio, R. J.; Wohlman, K. D.

2001-05-01

We are exploring the light curves of eclipsing binaries for the photometric signature of planets that may exist at the L4 and L5 Lagrange points of the stellar system. While no binaries are known to exist that strictly satisfy the stellar mass ratio constraint for the restricted three-body problem, the general solution would allow a planet formed at the L-point to remain there if there are no major perturbing bodies such as an additional planet. We have coined such objects "Trojan planets." The advantage of this approach is that the phases of the planetary eclipses are known. We picked systems with deep primary eclipses, to maximize the amount of system light eclipsed by the planet when in front of the hotter star. We also scanned the Finding List for Observers of Interactive Binary Stars, for G dwarf systems, but found only a few that were high inclination and detached. The target list includes QY Aql, YZ Aql, V442 Cas, SS Cet, S Cnc, VW Cyg, WW Cyg, RR Dra, RX Gem, RY Gem, VW Hya, Y Leo, TV Mon, BN Sct, UW Vir, AC UMa, and GSC 1657. We have concentrated on V442 Cas and YZ Aql, based on initial results that show anomalies in the light curves near the phases where a Trojan planet eclipse is expected. New work is being done on brighter systems by using a "spot filter," similar to that developed by Castellano (PASP 112, 821-6),2000), to allow longer exposures that provide brighter comparison stars. We will report on the observations made to date on several systems. We gratefully acknowledge the support of the National Science Foundation, through grants AST-9731062 and AST-0089248. We also appreciate the support of the Fund for Astrophysical Research. Gregory Shelton and Brenda Corbin, at the U.S. naval Observatory Library, have been indispensable in providing references for these binary systems. This research has made use of the Simbad database, operated at CDS, Strasbourg, France

The β1a Subunit of the Skeletal DHPR Binds to Skeletal RyR1 and Activates the Channel via Its 35-Residue C-Terminal Tail

PubMed Central

Rebbeck, Robyn T.; Karunasekara, Yamuna; Gallant, Esther M.; Board, Philip G.; Beard, Nicole A.; Casarotto, Marco G.; Dulhunty, Angela F.

2011-01-01

Although it has been suggested that the C-terminal tail of the β1a subunit of the skeletal dihyropyridine receptor (DHPR) may contribute to voltage-activated Ca2+ release in skeletal muscle by interacting with the skeletal ryanodine receptor (RyR1), a direct functional interaction between the two proteins has not been demonstrated previously. Such an interaction is reported here. A peptide with the sequence of the C-terminal 35 residues of β1a bound to RyR1 in affinity chromatography. The full-length β1a subunit and the C-terminal peptide increased [3H]ryanodine binding and RyR1 channel activity with an AC50 of 450–600 pM under optimal conditions. The effect of the peptide was dependent on cytoplasmic Ca2+, ATP, and Mg2+ concentrations. There was no effect of the peptide when channel activity was very low as a result of Mg2+ inhibition or addition of 100 nM Ca2+ (without ATP). Maximum increases were seen with 1–10 μM Ca2+, in the absence of Mg2+ inhibition. A control peptide with the C-terminal 35 residues in a scrambled sequence did not bind to RyR1 or alter [3H]ryanodine binding or channel activity. This high-affinity in vitro functional interaction between the C-terminal 35 residues of the DHPR β1a subunit and RyR1 may support an in vivo function of β1a during voltage-activated Ca2+ release. PMID:21320436

ATP interacts with the CPVT mutation-associated central domain of the cardiac ryanodine receptor.

PubMed

Blayney, Lynda; Beck, Konrad; MacDonald, Ewan; D'Cruz, Leon; Nomikos, Michail; Griffiths, Julia; Thanassoulas, Angelos; Nounesis, George; Lai, F Anthony

2013-10-01

This study was designed to determine whether the cardiac ryanodine receptor (RyR2) central domain, a region associated with catecholamine polymorphic ventricular tachycardia (CPVT) mutations, interacts with the RyR2 regulators, ATP and the FK506-binding protein 12.6 (FKBP12.6). Wild-type (WT) RyR2 central domain constructs (G(2236)to G(2491)) and those containing the CPVT mutations P2328S and N2386I, were expressed as recombinant proteins. Folding and stability of the proteins were examined by circular dichroism (CD) spectroscopy and guanidine hydrochloride chemical denaturation. The far-UV CD spectra showed a soluble stably-folded protein with WT and mutant proteins exhibiting a similar secondary structure. Chemical denaturation analysis also confirmed a stable protein for both WT and mutant constructs with similar two-state unfolding. ATP and caffeine binding was measured by fluorescence spectroscopy. Both ATP and caffeine bound with an EC50 of ~200-400μM, and the affinity was the same for WT and mutant constructs. Sequence alignment with other ATP binding proteins indicated the RyR2 central domain contains the signature of an ATP binding pocket. Interaction of the central domain with FKBP12.6 was tested by glutaraldehyde cross-linking and no association was found. The RyR2 central domain, expressed as a 'correctly' folded recombinant protein, bound ATP in accord with bioinformatics evidence of conserved ATP binding sequence motifs. An interaction with FKBP12.6 was not evident. CPVT mutations did not disrupt the secondary structure nor binding to ATP. Part of the RyR2 central domain CPVT mutation cluster, can be expressed independently with retention of ATP binding. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnesium inhibition of ryanodine-receptor calcium channels: evidence for two independent mechanisms.

PubMed

Laver, D R; Baynes, T M; Dulhunty, A F

1997-04-01

The gating of ryanodine receptor calcium release channels (RyRs) depends on myoplasmic Ca2+ and Mg2+ concentrations. RyRs from skeletal and cardiac muscle are activated by microm Ca2+ and inhibited by mm Ca2+ and Mg2+. 45Ca2+ release from skeletal SR vesicles suggests two mechanisms for Mg2+-inhibition (Meissner, Darling & Eveleth, 1986, Biochemistry 25:236-244). The present study investigates the nature of these mechanisms using measurements of single-channel activity from cardiac- and skeletal RyRs incorporated into planar lipid bilayers. Our measurements of Mg2+- and Ca2+-dependent gating kinetics confirm that there are two mechanisms for Mg2+ inhibition (Type I and II inhibition) in skeletal and cardiac RyRs. The mechanisms operate concurrently, are independent and are associated with different parts of the channel protein. Mg2+ reduces Po by competing with Ca2+ for the activation site (Type-I) or binding to more than one, and probably two low affinity inhibition sites which do not discriminate between Ca2+ and Mg2+ (Type-II). The relative contributions of the two inhibition mechanisms to the total Mg2+ effect depend on cytoplasmic [Ca2+] in such a way that Mg2+ inhibition has the properties of Types-I and II inhibition at low and high [Ca2+] respectively. Both mechanisms are equally important when [Ca2+] = 10 microm in cardiac RyRs or 1 microm in skeletal RyRs. We show that Type-I inhibition is not the sole mechanism responsible for Mg2+ inhibition, as is often assumed, and we discuss the physiological implications of this finding.

Spontaneous Ca2+ sparks and Ca2+ homeostasis in a minimal model of permeabilized ventricular myocytes

PubMed Central

Hartman, Jana M.; Sobie, Eric A.

2010-01-01

Many issues remain unresolved concerning how local, subcellular Ca2+ signals interact with bulk cellular concentrations to maintain homeostasis in health and disease. To aid in the interpretation of data obtained in quiescent ventricular myocytes, we present here a minimal whole cell model that accounts for both localized (subcellular) and global (cellular) aspects of Ca2+ signaling. Using a minimal formulation of the distribution of local [Ca2+] associated with a large number of Ca2+-release sites, the model simulates both random spontaneous Ca2+ sparks and the changes in myoplasmic and sarcoplasmic reticulum (SR) [Ca2+] that result from the balance between stochastic release and reuptake into the SR. Ca2+-release sites are composed of clusters of two-state ryanodine receptors (RyRs) that exhibit activation by local cytosolic [Ca2+] but no inactivation or regulation by luminal Ca2+. Decreasing RyR open probability in the model causes a decrease in aggregate release flux and an increase in SR [Ca2+], regardless of whether RyR inhibition is mediated by a decrease in RyR open dwell time or an increase in RyR closed dwell time. The same balance of stochastic release and reuptake can be achieved, however, by either high-frequency/short-duration or low-frequency/long-duration Ca2+ sparks. The results are well correlated with recent experimental observations using pharmacological RyR inhibitors and clarify those aspects of the release-reuptake balance that are inherent to the coupling between local and global Ca2+ signals and those aspects that depend on molecular-level details. The model of Ca2+ sparks and homeostasis presented here can be a useful tool for understanding changes in cardiac Ca2+ release resulting from drugs, mutations, or acquired diseases. PMID:20852058

Quality of life and nutritional consequences after aboral pouch reconstruction following total gastrectomy for gastric cancer: randomized controlled trial CCG1101.

PubMed

Ito, Yuichi; Yoshikawa, Takaki; Fujiwara, Michitaka; Kojima, Hiroshi; Matsui, Takanori; Mochizuki, Yoshinari; Cho, Haruhiko; Aoyama, Toru; Ito, Seiji; Misawa, Kazunari; Nakayama, Hiroshi; Morioka, Yuki; Ishiyama, Akiharu; Tanaka, Chie; Morita, Satoshi; Sakamoto, Junichi; Kodera, Yasuhiro

2016-07-01

Total gastrectomy has detrimental effects on postoperative nutritional status and quality of life (QOL), but it is often unavoidable in the treatment of gastric cancer. Roux-en-Y (RY) is the most common reconstruction method following total gastrectomy. Trials to explore other means of reconstruction have been conducted but have failed to identify a method that is globally accepted. Aboral pouch reconstruction (AP), in which an anisoperistaltic jejunal pouch is created in the Y limb of the RY reconstruction, is considered effective and technically feasible. A prospective randomized trial was conducted to compare AP with RY. Gastric cancer patients requiring total gastrectomy for R0 resection were randomly assigned during surgery to receive either RY (n = 51) or AP (n = 49). Postoperative QOL as assessed by the EORTC QLQ-C30 and STO22, body composition, and morbidity were compared between the two reconstruction methods. The physical functioning score of the QLQ-C30 was selected as the primary endpoint. The incidences of postoperative complications were similar between the two groups (29 % in the RY group and 27 % in the AP group). No significant difference was observed in the physical functioning score, and the superiority of AP was demonstrated only for the nausea and vomiting score at 12 months (p = 0.041) and the reflux score at 1 month (p = 0.036). No significant differences were observed in body composition or serum biochemistry. Although AP was safely implemented, no increased benefits in nutritional or QOL-related parameters were observed for this method over RY within 12 months postoperatively.

Single- and double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y plus hepaticojejunostomy anastomosis and Whipple resection.

PubMed

Itokawa, Fumihide; Itoi, Takao; Ishii, Kentaro; Sofuni, Atsushi; Moriyasu, Fuminori

2014-04-01

In patients with Roux-en-Y hepaticojejunostomy (HJ with R-Y) and Whipple resection, endoscopic retrograde cholangiopancreatography (ERCP) can be challenging. We report our experience with ERCP using balloon-assisted enteroscopy (BAE) (BAE-ERCP) in patients with HJ with R-Y, and Whipple resection. BAE-ERCP procedures were carried out in 62 patients (HJ with R-Y:Whipple resection=34:28). Overall, the rates of reaching the anastomosis were 85.3% (29/34) in HJ with R-Y and 96.4% (27/28) in Whipple resection. In terms of HJ with R-Y, insertion success rate by standard single-balloon enteroscopy (SBE) was 89.3% (25/28). Insertion success rate by short BAE, including SBE and double-balloon enteroscopy (DBE), was 50% (3/6). There was a statistically significant difference of insertion success rate between standard long BE and short BE (P=0.021). However, in the Whipple patients, insertion success rate by standard and short SBE was 93.8% (15/16) and 91.7% (11/12), respectively. Initial insertion success rate by short BAE in Whipple patients was significantly higher than in HJ with R-Y (91.7% vs 50%, P=0.045). Therapeutic interventions included dilation of anastomosis stricture, stone extraction, endoscopic mechanical lithotripsy, biliary stent placement, stent extraction, endoscopic nasobiliary drainage, direct cholangioscopy, and electrohydraulic lithotripsy. Our HJ with R-Y series and Whipple series treatment success rate was 90% (18/20) and 95.0% (19/20), respectively. BAE-ERCP enabled ERCP to be carried out in patients with HJ. It is considered safe and feasible. Further experience and device improvement are needed. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Medicinal effect and its JP2/RyR2-based mechanism of Smilax glabra flavonoids on angiotensin II-induced hypertrophy model of cardiomyocytes.

PubMed

Cai, Yueqin; Tu, Jue; Pan, Shuizhen; Jiang, Jianping; Shou, Qiyang; Ling, Yun; Chen, Yunxiang; Wang, Dejun; Yang, Weiji; Shan, Letian; Chen, Minli

2015-07-01

Rhizome and root of Smilax glabra Roxb (Liliaceae family) is a widely used traditional Chinese medicine (TCM) named Tu-fu-ling (TFL) for cardiac disease therapy. The TFL flavonoids (TFLF) has been extracted and proven to possess the anti-cardiac hypertrophy effect in our previous reports. Such effect could be mediated by the modulation of intracellular Ca(2+) flux in myocardial cells, in which junctophilin-2 (JP2) and ryanodine receptor 2 (RyR2) play an important role. However, its mechanism of the anti-cardiac hypertrophy effect remains unclarified. 2μmol/L Ang II was applied to induce hypertrophy model of rat primary cardiomyocytes. After treatment of TFLF at 0.25, 0.5 and 1.0mg/ml, the cell size was microscopic measured, and the protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were estimated by immunofluorescence imaging, ELISA and real-time PCR assay. Obvious hypertrophy of cardiomyocytes was induced by Ang II but reversed by TFLF from 0.5 to 1.0mg/ml. The protein and mRNA expressions of JP2 and RyR2 in cardiomyocytes were also inhibited by Ang II but restored by TFLF at its dose range. Such effect of TFLF was exerted at a dose dependent manner, which was even better than that of verapamil. Our findings may evidence the correlation between JP2/RyR2 and myocardiac hypertrophy, and indicate the JP2/RyR2-mediated anti-hypertrophy mechanism of TFLF for the first time. It deserves to be developed as a promising TCM candidate of new drug for myocardial hypertrophy treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure.

PubMed

van Oort, Ralph J; McCauley, Mark D; Dixit, Sayali S; Pereira, Laetitia; Yang, Yi; Respress, Jonathan L; Wang, Qiongling; De Almeida, Angela C; Skapura, Darlene G; Anderson, Mark E; Bers, Donald M; Wehrens, Xander H T

2010-12-21

approximately half of patients with heart failure die suddenly as a result of ventricular arrhythmias. Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain unknown. We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias. mice in which the S2814 Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 is constitutively activated (S2814D) develop pathological sarcoplasmic reticulum Ca(2+) release events, resulting in reduced sarcoplasmic reticulum Ca(2+) load on confocal microscopy. These Ca(2+) release events are associated with increased RyR2 open probability in lipid bilayer preparations. At baseline, young S2814D mice have structurally and functionally normal hearts without arrhythmias; however, they develop sustained ventricular tachycardia and sudden cardiac death on catecholaminergic provocation by caffeine/epinephrine or programmed electric stimulation. Young S2814D mice have a significant predisposition to sudden arrhythmogenic death after transverse aortic constriction surgery. Finally, genetic ablation of the Ca(2+)/calmodulin-dependent protein kinase II site on RyR2 (S2814A) protects mutant mice from pacing-induced arrhythmias versus wild-type mice after transverse aortic constriction surgery. our results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure.

Enantioselectivity of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) Atropisomers toward Ryanodine Receptors (RyRs) and Their Influences on Hippocampal Neuronal Networks.

PubMed

Feng, Wei; Zheng, Jing; Robin, Gaëlle; Dong, Yao; Ichikawa, Makoto; Inoue, Yoshihisa; Mori, Tadashi; Nakano, Takeshi; Pessah, Isaac N

2017-12-19

Nineteen ortho-substituted PCBs are chiral and found enantioselectively enriched in ecosystems. Their differential actions on biological targets are not understood. PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a chiral PCB of current environmental relevance, is among the most potent toward modifying ryanodine receptors (RyR) function and Ca 2+ signaling. PCB 95 enantiomers are separated and assigned aR- and aS-PCB 95 using three chiral-column HPLC and circular dichroism spectroscopy. Studies of RyR1-enriched microsomes show aR-PCB 95 with >4× greater potency (EC 50 = 0.20 ± 0.05 μM), ∼ 1.3× higher efficacy (B max = 3.74 ± 0.07 μM) in [ 3 H]Ryanodine-binding and >3× greater rates (R = 7.72 ± 0.31 nmol/sec/mg) of Ca 2+ efflux compared with aS-PCB 95, whereas racemate has intermediate activity. aR-PCB 95 has modest selectivity for RyR2, and lower potency than racemate toward the RyR isoform mixture in brain membranes. Chronic exposure of hippocampal neuronal networks to nanomolar PCB 95 during a critical developmental period shows divergent influences on synchronous Ca 2+ oscillation (SCO): rac-PCB 95 increasing and aR-PCB 95 decreasing SCO frequency at 50 nM, although the latter's effects are nonmonotonic at higher concentration. aS-PCB95 shows the greatest influence on inhibiting responses to 20 Hz electrical pulse trains. Considering persistence of PCB 95 in the environment, stereoselectivity toward RyRs and developing neuronal networks may clarify health risks associated with enantioisomeric enrichment of PCBs.

Design of a concise Féry-prism hyperspectral imaging system based on multi-configuration

NASA Astrophysics Data System (ADS)

Dong, Wei; Nie, Yun-feng; Zhou, Jin-song

2013-08-01

In order to meet the needs of space borne and airborne hyperspectral imaging system for light weight, simplification and high spatial resolution, a novel design of Féry-prism hyperspectral imaging system based on Zemax multi-configuration method is presented. The novel structure is well arranged by analyzing optical monochromatic aberrations theoretically, and the optical structure of this design is concise. The fundamental of this design is Offner relay configuration, whereas the secondary mirror is replaced by Féry-prism with curved surfaces and a reflective front face. By reflection, the light beam passes through the Féry-prism twice, which promotes spectral resolution and enhances image quality at the same time. The result shows that the system can achieve light weight and simplification, compared to other hyperspectral imaging systems. Composed of merely two spherical mirrors and one achromatized Féry-prism to perform both dispersion and imaging functions, this structure is concise and compact. The average spectral resolution is 6.2nm; The MTFs for 0.45~1.00um spectral range are greater than 0.75, RMSs are less than 2.4um; The maximal smile is less than 10% pixel, while the keystones is less than 2.8% pixel; image quality approximates the diffraction limit. The design result shows that hyperspectral imaging system with one modified Féry-prism substituting the secondary mirror of Offner relay configuration is feasible from the perspective of both theory and practice, and possesses the merits of simple structure, convenient optical alignment, and good image quality, high resolution in space and spectra, adjustable dispersive nonlinearity. The system satisfies the requirements of airborne or space borne hyperspectral imaging system.

Imaging Ca2+ nanosparks in heart with a new targeted biosensor.

PubMed

Shang, Wei; Lu, Fujian; Sun, Tao; Xu, Jiejia; Li, Lin-Lin; Wang, Yanru; Wang, Gang; Chen, Liangyi; Wang, Xianhua; Cannell, Mark B; Wang, Shi-Qiang; Cheng, Heping

2014-01-31

In cardiac dyads, junctional Ca2+ directly controls the gating of the ryanodine receptors (RyRs), and is itself dominated by RyR-mediated Ca2+ release from the sarcoplasmic reticulum. Existing probes do not report such local Ca2+ signals because of probe diffusion, so a junction-targeted Ca2+ sensor should reveal new information on cardiac excitation-contraction coupling and its modification in disease states. To investigate Ca2+ signaling in the nanoscopic space of cardiac dyads by targeting a new sensitive Ca2+ biosensor (GCaMP6f) to the junctional space. By fusing GCaMP6f to the N terminus of triadin 1 or junctin, GCaMP6f-triadin 1/junctin was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. This membrane protein-tagged biosensor displayed ≈4× faster kinetics than native GCaMP6f. Confocal imaging revealed junctional Ca2+ transients (Ca2+ nanosparks) that were ≈50× smaller in volume than conventional Ca2+ sparks (measured with diffusible indicators). The presence of the biosensor did not disrupt normal Ca2+ signaling. Because no indicator diffusion occurred, the amplitude and timing of release measurements were improved, despite the small recording volume. We could also visualize coactivation of subclusters of RyRs within a single junctional region, as well as quarky Ca2+ release events. This new, targeted biosensor allows selective visualization and measurement of nanodomain Ca2+ dynamics in intact cells and can be used to give mechanistic insights into dyad RyR operation in health and in disease states such as when RyRs become orphaned.

Projective limits of state spaces II. Quantum formalism

NASA Astrophysics Data System (ADS)

Lanéry, Suzanne; Thiemann, Thomas

2017-06-01

In this series of papers, we investigate the projective framework initiated by Kijowski (1977) and Okołów (2009, 2014, 2013), which describes the states of a quantum theory as projective families of density matrices. A short reading guide to the series can be found in Lanéry (2016). After discussing the formalism at the classical level in a first paper (Lanéry, 2017), the present second paper is devoted to the quantum theory. In particular, we inspect in detail how such quantum projective state spaces relate to inductive limit Hilbert spaces and to infinite tensor product constructions (Lanéry, 2016, subsection 3.1) [1]. Regarding the quantization of classical projective structures into quantum ones, we extend the results by Okołów (2013), that were set up in the context of linear configuration spaces, to configuration spaces given by simply-connected Lie groups, and to holomorphic quantization of complex phase spaces (Lanéry, 2016, subsection 2.2) [1].

Structural basis for gating and activation of RyR1

PubMed Central

des Georges, Amédée; Clarke, Oliver B.; Zalk, Ran; Yuan, Qi; Condon, Kendall J.; Grassucci, Robert A.; Hendrickson, Wayne A.; Marks, Andrew R.; Frank, Joachim

2016-01-01

Summary The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca2+) release channel required for skeletal muscle contraction. Here we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca2+, ATP and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca2+ alone induce conformational changes in the cytoplasmic assembly (‘priming’), without pore dilation. In contrast, in the presence of all three activating ligands, high-resolution reconstructions of open and closed states of RyR1 were obtained from the same sample, enabling analyses of conformational changes associated with gating. Gating involves global conformational changes in the cytosolic assembly accompanied by local changes in the transmembrane domain, which include bending of the S6 transmembrane segment and consequent pore dilation, displacement and deformation of the S4-S5 linker, and conformational changes in the pseudo-voltage-sensor domain. PMID:27662087

GSC 02505-00411: A new delta Sct star in the field of RZ LMi

NASA Astrophysics Data System (ADS)

Ishioka, R.; Kokumbaeva, R.

2017-04-01

We present the time series analysis of CCD photometry from ``EAST'' Zeiss-1000 telescope at Tien-Shan Astronomical Observatory (Almaty, Kazakhstan) for GSC 02505-00411. GSC 02505-00411 is a new multi-frequency delta Scuti variable with a primary frequency of 43.84 c/d.

The Cytoplasmic Region of Inner Helix S6 Is an Important Determinant of Cardiac Ryanodine Receptor Channel Gating.

PubMed

Sun, Bo; Guo, Wenting; Tian, Xixi; Yao, Jinjing; Zhang, Lin; Wang, Ruiwu; Chen, S R Wayne

2016-12-09

The ryanodine receptor (RyR) channel pore is formed by four S6 inner helices, with its intracellular gate located at the S6 helix bundle crossing region. The cytoplasmic region of the extended S6 helix is held by the U motif of the central domain and is thought to control the opening and closing of the S6 helix bundle. However, the functional significance of the S6 cytoplasmic region in channel gating is unknown. Here we assessed the role of the S6 cytoplasmic region in the function of cardiac RyR (RyR2) via structure-guided site-directed mutagenesis. We mutated each residue in the S6 cytoplasmic region of the mouse RyR2 ( 4876 QQEQVKEDM 4884 ) and characterized their functional impact. We found that mutations Q4876A, V4880A, K4881A, and M4884A, located mainly on one side of the S6 helix that faces the U motif, enhanced basal channel activity and the sensitivity to Ca 2+ or caffeine activation, whereas mutations Q4877A, E4878A, Q4879A, and D4883A, located largely on the opposite side of S6, suppressed channel activity. Furthermore, V4880A, a cardiac arrhythmia-associated mutation, markedly enhanced the frequency of spontaneous openings and the sensitivity to cytosolic and luminal Ca 2+ activation of single RyR2 channels. V4880A also increased the propensity and reduced the threshold for arrhythmogenic spontaneous Ca 2+ release in HEK293 cells. Collectively, our data suggest that interactions between the cytoplasmic region of S6 and the U motif of RyR2 are important for stabilizing the closed state of the channel. Mutations in the S6/U motif domain interface likely destabilize the closed state of RyR2, resulting in enhanced basal channel activity and sensitivity to activation and increased propensity for spontaneous Ca 2+ release and cardiac arrhythmias. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison of myoplasmic calcium movements during excitation–contraction coupling in frog twitch and mouse fast-twitch muscle fibers

PubMed Central

Hollingworth, Stephen

2013-01-01

Single twitch fibers from frog leg muscles were isolated by dissection and micro-injected with furaptra, a rapidly responding fluorescent Ca2+ indicator. Indicator resting fluorescence (FR) and the change evoked by an action potential (ΔF) were measured at long sarcomere length (16°C); ΔF/FR was scaled to units of ΔfCaD, the change in fraction of the indicator in the Ca2+-bound form. ΔfCaD was simulated with a multicompartment model of the underlying myoplasmic Ca2+ movements, and the results were compared with previous measurements and analyses in mouse fast-twitch fibers. In frog fibers, sarcoplasmic reticulum (SR) Ca2+ release evoked by an action potential appears to be the sum of two components. The time course of the first component is similar to that of the entire Ca2+ release waveform in mouse fibers, whereas that of the second component is severalfold slower; the fractional release amounts are ∼0.8 (first component) and ∼0.2 (second component). Similar results were obtained in frog simulations with a modified model that permitted competition between Mg2+ and Ca2+ for occupancy of the regulatory sites on troponin. An anatomical basis for two release components in frog fibers is the presence of both junctional and parajunctional SR Ca2+ release channels (ryanodine receptors [RyRs]), whereas mouse fibers (usually) have only junctional RyRs. Also, frog fibers have two RyR isoforms, RyRα and RyRβ, whereas the mouse fibers (usually) have only one, RyR1. Our simulations suggest that the second release component in frog fibers functions to supply extra Ca2+ to activate troponin, which, in mouse fibers, is not needed because of the more favorable location of their triadic junctions (near the middle of the thin filament). We speculate that, in general, parajunctional RyRs permit increased myofilament activation in fibers whose triadic junctions are located at the z-line. PMID:23630340

The FUSE Survey of Algol-Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine J.; Andersson, B.; Ake, T. B.; Sankrit, R.

2006-12-01

A survey of Algol binaries at random phases is currently being carried through with the FUSE spacecraft as part of the FUSE survey and supplemental program. A similar program was undertaken in FUSE Cycle 3. Both programs have produced multiple observations of 12 Algol systems with periods ranging from 1.2 37 d and include direct-impact and disk systems. We report on the status of the program. The absence of O VI absorption in the systems observed to date allows us to place an upper limit on the column density and temperature of the High Temperature Accretion Region, HTAR ( 100,000 K) confirmed in some Algols from earlier IUE data. The HTAR plasma component appears to be distinct from an O VI-emitting polar plasma discovered in FUSE totality observations of RY Per, V356 Sgr, and TT Hya. New observations of the direct-impact system U Cep have provided more information on the geometry and mass flow (including a splash plasma) in the vicinity of a hot spot at phase 0.90 that was discovered earlier. The extent of disk asymmetries in the long period ( 33 d) systems SX Cas and RX Cas is discussed. Models for direct-impact and the disk systems will be presented. The authors appreciate support from NASA grants NAG5-12253, NNG04GL17G, and NAS5-32985.

Schoolyard Shade and Sun Exposure: Assessment of Personal Monitoring During Children's Physical Activity.

PubMed

Vanos, Jennifer K; McKercher, Grant R; Naughton, Kylie; Lochbaum, Marc

2017-07-01

Childhood exposure to ultraviolet radiation (UVR) is a major risk factor for the development of melanoma later in life. However, it is challenging to accurately determine personal outdoor exposure to UVR, specifically erythemally weighted UVR (UV E ry ), due to technological constraints, variable time-activity patterns, and the influence of outdoor environmental design. To address this challenge, this study utilized mobile and stationary techniques to examine the UV E ry exposures of 14 children in a schoolyard in Lubbock, TX, in spring 2016. The aims of the study were to examine the influence of artificial shade on personal UV E ry exposures and to assess full sun exposure ratios (ERs) within the same playground microenvironment. On average, personal wrist dosimeters worn during play in the sun measured 18% of the total onsite UV E ry measured by a stationary UV pyranometer. Shade was found to significantly reduce the personal UV E ry exposures by 55%, UVB 280-315 nm exposures by 91%, and the overall solar radiation by 84%. Substantial benefits can be garnered through focused design of children's recreational space to utilize shade-both natural and artificial-to reduce UVR exposures during play, and to extend safe outdoor stays. Finally, although the wrist is a practical location for a dosimeter, it often underestimates full exposures, particularly during physical activity. © 2017 The American Society of Photobiology.

Expression analysis of G Protein-Coupled Receptors in mouse macrophages

PubMed Central

Lattin, Jane E; Schroder, Kate; Su, Andrew I; Walker, John R; Zhang, Jie; Wiltshire, Tim; Saijo, Kaoru; Glass, Christopher K; Hume, David A; Kellie, Stuart; Sweet, Matthew J

2008-01-01

Background Monocytes and macrophages express an extensive repertoire of G Protein-Coupled Receptors (GPCRs) that regulate inflammation and immunity. In this study we performed a systematic micro-array analysis of GPCR expression in primary mouse macrophages to identify family members that are either enriched in macrophages compared to a panel of other cell types, or are regulated by an inflammatory stimulus, the bacterial product lipopolysaccharide (LPS). Results Several members of the P2RY family had striking expression patterns in macrophages; P2ry6 mRNA was essentially expressed in a macrophage-specific fashion, whilst P2ry1 and P2ry5 mRNA levels were strongly down-regulated by LPS. Expression of several other GPCRs was either restricted to macrophages (e.g. Gpr84) or to both macrophages and neural tissues (e.g. P2ry12, Gpr85). The GPCR repertoire expressed by bone marrow-derived macrophages and thioglycollate-elicited peritoneal macrophages had some commonality, but there were also several GPCRs preferentially expressed by either cell population. Conclusion The constitutive or regulated expression in macrophages of several GPCRs identified in this study has not previously been described. Future studies on such GPCRs and their agonists are likely to provide important insights into macrophage biology, as well as novel inflammatory pathways that could be future targets for drug discovery. PMID:18442421

The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation

PubMed Central

Lesiak, Adam; Zhu, Mingyan; Chen, Hao; Appleyard, Suzanne M.; Impey, Soren; Wayman, Gary A.

2014-01-01

Non–dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca2+ oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation. Nanomolar concentrations of PCB 95, a NDL congener with potent RyR activity, significantly increased spine density and the frequency of miniature EPSCs in primary dissociated rat hippocampal cultures coincident with upregulation of miR132. Inhibition of RyR, CREB, or miR132 as well as expression of a mutant p250GAP cDNA construct that is not suppressed by miR132 blocked PCB 95 effects on spines and miniature EPSCs. PCB 95 also induced spine formation via RyR- and miR132-dependent mechanisms in hippocampal slice cultures. These data demonstrate a novel mechanism of PCB developmental neurotoxicity whereby RyR sensitization modulates spine formation and synaptogenesis via CREB-mediated miR132 upregulation, which in turn suppresses the translation of p250GAP, a negative regulator of synaptogenesis. In light of recent evidence implicating miR132 dysregulation in Rett syndrome and schizophrenia, these findings identify NDL PCBs as potential environmental risk factors for neurodevelopmental disorders. PMID:24431430

M16

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

M16 is an open cluster in the constellation Serpens, associated with the EAGLE NEBULA (1 degree north and 2.5 degrees west of γ Scuti). It was discovered by de Chéseaux in 1746 as a `cluster of stars' and sits on the next inner spiral arm of the galaxy away from us next to M17....

The 2006-2007 Observing Campaign On VX Hydrae

NASA Astrophysics Data System (ADS)

Templeton, Matthew R.; Samolyk, G.; Dvorak, S.; Poklar, R.; Butterworth, N.; Gerner, H. S.

2009-12-01

We present the results of the 2006-2007 observing campaign on the double-mode delta Scuti star VX Hydrae. Nearly 8800 V-band CCD observations were obtained during the two observing seasons. Although the data were taken with small telescopes (0.3-m or less, using consumer-grade CCD cameras), the data quality is very high, enabling the detection of variability at the millimagnitude level at some frequencies. Analysis of the data yields only two primary pulsation frequencies: f(0) = 4.4765 c/d, and f(1) = 5.7899 c/d. The two modes have comparable amplitude, although the amplitude of f(1) appears to have increased slightly from 2006 to 2007 by 0.01 mag. Only two pulsation modes are detected, but at least 18 additional linear combination frequencies are also clearly detected, some having amplitudes as low as 1 mmag, resulting in an incredibly rich Fourier spectrum. We discuss the evidence for amplitude variation in VX Hydrae, along with prospects for future study of this and other similar delta Scuti stars by AAVSO observers.

Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model

PubMed Central

Lu, Luyao; Xia, Ling; Zhu, Xiuwei

2012-01-01

Cardiac cells with heart failure are usually characterized by impairment of Ca2+ handling with smaller SR Ca2+ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca2+ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca2+ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca2+ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca2+ dynamics is unstable and Ca2+ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level. PMID:23056145

Bipartite Structure of the 5s Ribosomal Gene Family in a Drosophila Melanogaster Strain, and Its Evolutionary Implications

PubMed Central

Samson, M. L.; Wegnez, M.

1988-01-01

Knowledge of multigenic family organization should provide insight into their mode of evolution. Accordingly, we characterized the 5S ribosomal gene family in the Drosophila melanogaster strain ry(506). The 5S genes in this strain display a striking HindIII restriction difference compared to the ``standard'' D. melanogaster 5S genes. The sequence of three ry(506) 5S genes was determined. We show that the HindIII restriction site heterogeneity within the ry(506) 5S family most probably results from the same point mutation, suggesting that a single 5S variant was propagated into the 5S cluster of this strain. Furthermore, we demonstrate that the structural organization of the 5S genes in ry(506) is a bipartite structure, i.e., that about 40% of the 5S genes constitute a HindIII(+)/HindIII(-) mixed cluster, while those remaining constitute an homogeneous HindIII(-) cluster. The events which might lead to such an heterogeneous pattern are discussed from an evolutionary point of view. PMID:2835290

A chemical chaperone improves muscle function in mice with a RyR1 mutation.

PubMed

Lee, Chang Seok; Hanna, Amy D; Wang, Hui; Dagnino-Acosta, Adan; Joshi, Aditya D; Knoblauch, Mark; Xia, Yan; Georgiou, Dimitra K; Xu, Jianjun; Long, Cheng; Amano, Hisayuki; Reynolds, Corey; Dong, Keke; Martin, John C; Lagor, William R; Rodney, George G; Sahin, Ergun; Sewry, Caroline; Hamilton, Susan L

2017-03-24

Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca 2+ release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca 2+ transient, resting cytosolic Ca 2+ levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production. Treatment of mice carrying the I4895T mutation with a chemical chaperone, sodium 4-phenylbutyrate (4PBA), reduces ER stress/UPR and improves muscle function, but does not restore SR Ca 2+ transients in I4895T fibres to wild type levels, suggesting that decreased SR Ca 2+ release is not the major driver of the myopathy. These findings suggest that 4PBA, an FDA-approved drug, has potential as a therapeutic intervention for RyR1 myopathies that are associated with ER stress.

A chemical chaperone improves muscle function in mice with a RyR1 mutation

PubMed Central

Lee, Chang Seok; Hanna, Amy D.; Wang, Hui; Dagnino-Acosta, Adan; Joshi, Aditya D.; Knoblauch, Mark; Xia, Yan; Georgiou, Dimitra K.; Xu, Jianjun; Long, Cheng; Amano, Hisayuki; Reynolds, Corey; Dong, Keke; Martin, John C.; Lagor, William R.; Rodney, George G.; Sahin, Ergun; Sewry, Caroline; Hamilton, Susan L.

2017-01-01

Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca2+ release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca2+ transient, resting cytosolic Ca2+ levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production. Treatment of mice carrying the I4895T mutation with a chemical chaperone, sodium 4-phenylbutyrate (4PBA), reduces ER stress/UPR and improves muscle function, but does not restore SR Ca2+ transients in I4895T fibres to wild type levels, suggesting that decreased SR Ca2+ release is not the major driver of the myopathy. These findings suggest that 4PBA, an FDA-approved drug, has potential as a therapeutic intervention for RyR1 myopathies that are associated with ER stress. PMID:28337975

Phosphorylation-Dependent Regulation of Ryanodine Receptors

PubMed Central

Marx, Steven O.; Reiken, Steven; Hisamatsu, Yuji; Gaburjakova, Marta; Gaburjakova, Jana; Yang, Yi-Ming; Rosemblit, Nora; Marks, Andrew R.

2001-01-01

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function. PMID:11352932

Potassium dependent rescue of a myopathy with core-like structures in mouse

PubMed Central

Hanson, M Gartz; Wilde, Jonathan J; Moreno, Rosa L; Minic, Angela D; Niswander, Lee

2015-01-01

Myopathies decrease muscle functionality. Mutations in ryanodine receptor 1 (RyR1) are often associated with myopathies with microscopic core-like structures in the muscle fiber. In this study, we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with core-like structures. The RyR1 mutation decreases sensitivity to activated calcium release and myoplasmic calcium levels, subsequently affecting mitochondrial calcium and ATP production. Mutant muscle shows a persistent potassium leak and disrupted expression of regulators of potassium homeostasis. Inhibition of KATP channels or increasing interstitial potassium by diet or FDA-approved drugs can reverse the muscle weakness, fatigue-like physiology and pathology. We identify regulators of potassium homeostasis as biomarkers of disease that may reveal therapeutic targets in human patients with myopathy of central core disease (CCD). Altogether, our results suggest that amelioration of potassium leaks through potassium homeostasis mechanisms may minimize muscle damage of myopathies due to certain RyR1 mutations. DOI: http://dx.doi.org/10.7554/eLife.02923.001 PMID:25564733

Calsequestrin mediates changes in spontaneous calcium release profiles.

PubMed

Tania, Nessy; Keener, James P

2010-08-07

Calsequestrin (CSQ) is the primary calcium buffer within the sarcoplasmic reticulum (SR) of cardiac cells. It has also been identified as a regulator of Ryanodine receptor (RyR) calcium release channels by serving as a SR luminal sensor. When calsequestrin is free and unbound to calcium, it can bind to RyR and desensitize the channel from cytoplasmic calcium activation. In this paper, we study the role of CSQ as a buffer and RyR luminal sensor using a mechanistic model of RyR-CSQ interaction. By using various asymptotic approximations and mean first exit time calculation, we derive a minimal model of a calcium release unit which includes CSQ dependence. Using this model, we then analyze the effect of changing CSQ expression on the calcium release profile and the rate of spontaneous calcium release. We show that because of its buffering capability, increasing CSQ increases the spark duration and size. However, because of luminal sensing effects, increasing CSQ depresses the basal spark rate and increases the critical SR level for calcium release termination. Finally, we show that with increased bulk cytoplasmic calcium concentration, the CRU model exhibits deterministic oscillations.

Tripeptidyl Peptidase II Regulates Sperm Function by Modulating Intracellular Ca2+ Stores via the Ryanodine Receptor

PubMed Central

Zhou, Yuchuan; Ru, Yanfei; Wang, Chunmei; Wang, Shoulin; Zhou, Zuomin; Zhang, Yonglian

2013-01-01

Recent studies have identified Ca2+ stores in sperm cells; however, it is not clear whether these Ca2+ stores are functional and how they are mobilized. Here, in vitro and in vivo, we determined that tripeptidyl peptidase II antagonists strongly activated the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. We demonstrated that in the absence of Ca2+, TPIII antagonists elevated the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ could be blocked by the inhibitors of ryanodine receptors (RyRs) which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+. Consistent with these results, indirect immunofluorescence assay using anti-RyR antibodies further validated the presence of RyR3 in the acrosomal region of mature sperm. Thus, TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 RyR. PMID:23818952

Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant

NASA Astrophysics Data System (ADS)

Yuchi, Zhiguang; Yuen, Siobhan M. Wong King; Lau, Kelvin; Underhill, Ainsley Q.; Cornea, Razvan L.; Fessenden, James D.; van Petegem, Filip

2015-08-01

Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca2+-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

CGP-37157 inhibits the sarcoplasmic reticulum Ca²+ ATPase and activates ryanodine receptor channels in striated muscle.

PubMed

Neumann, Jake T; Diaz-Sylvester, Paula L; Fleischer, Sidney; Copello, Julio A

2011-01-01

7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one [CGP-37157 (CGP)], a benzothiazepine derivative of clonazepam, is commonly used as a blocker of the mitochondrial Na+/Ca²+ exchanger. However, evidence suggests that CGP could also affect other targets, such as L-type Ca²+ channels and plasmalemma Na+/Ca²+ exchanger. Here, we tested the possibility of a direct modulation of ryanodine receptor channels (RyRs) and/or sarco/endoplasmic reticulum Ca²+-stimulated ATPase (SERCA) by CGP. In the presence of ruthenium red (inhibitor of RyRs), CGP decreased SERCA-mediated Ca²+ uptake of cardiac and skeletal sarcoplasmic reticulum (SR) microsomes (IC₅₀ values of 6.6 and 9.9 μM, respectively). The CGP effects on SERCA activity correlated with a decreased V(max) of ATPase activity of SERCA-enriched skeletal SR fractions. CGP (≥ 5 μM) also increased RyR-mediated Ca²+ leak from skeletal SR microsomes. Planar bilayer studies confirmed that both cardiac and skeletal RyRs are directly activated by CGP (EC(50) values of 9.4 and 12.0 μM, respectively). In summary, we found that CGP inhibits SERCA and activates RyR channels. Hence, the action of CGP on cellular Ca²+ homeostasis reported in the literature of cardiac, skeletal muscle, and other nonmuscle systems requires further analysis to take into account the contribution of all CGP-sensitive Ca²+ transporters.

CGP-37157 Inhibits the Sarcoplasmic Reticulum Ca2+ ATPase and Activates Ryanodine Receptor Channels in Striated Muscle

PubMed Central

Neumann, Jake T.; Diaz-Sylvester, Paula L.; Fleischer, Sidney

2011-01-01

7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one [CGP-37157 (CGP)], a benzothiazepine derivative of clonazepam, is commonly used as a blocker of the mitochondrial Na+/Ca2+ exchanger. However, evidence suggests that CGP could also affect other targets, such as L-type Ca2+ channels and plasmalemma Na+/Ca2+ exchanger. Here, we tested the possibility of a direct modulation of ryanodine receptor channels (RyRs) and/or sarco/endoplasmic reticulum Ca2+-stimulated ATPase (SERCA) by CGP. In the presence of ruthenium red (inhibitor of RyRs), CGP decreased SERCA-mediated Ca2+ uptake of cardiac and skeletal sarcoplasmic reticulum (SR) microsomes (IC50 values of 6.6 and 9.9 μM, respectively). The CGP effects on SERCA activity correlated with a decreased Vmax of ATPase activity of SERCA-enriched skeletal SR fractions. CGP (≥5 μM) also increased RyR-mediated Ca2+ leak from skeletal SR microsomes. Planar bilayer studies confirmed that both cardiac and skeletal RyRs are directly activated by CGP (EC50 values of 9.4 and 12.0 μM, respectively). In summary, we found that CGP inhibits SERCA and activates RyR channels. Hence, the action of CGP on cellular Ca2+ homeostasis reported in the literature of cardiac, skeletal muscle, and other nonmuscle systems requires further analysis to take into account the contribution of all CGP-sensitive Ca2+ transporters. PMID:20923851

Inositol trisphosphate receptor-mediated Ca2+ signalling stimulates mitochondrial function and gene expression in core myopathy patients.

PubMed

Suman, Matteo; Sharpe, Jenny A; Bentham, Robert B; Kotiadis, Vassilios N; Menegollo, Michela; Pignataro, Viviana; Molgó, Jordi; Muntoni, Francesco; Duchen, Michael R; Pegoraro, Elena; Szabadkai, Gyorgy

2018-07-01

Core myopathies are a group of childhood muscle disorders caused by mutations of the ryanodine receptor (RyR1), the Ca2+ release channel of the sarcoplasmic reticulum. These mutations have previously been associated with elevated inositol trisphosphate receptor (IP3R) levels in skeletal muscle myotubes derived from patients. However, the functional relevance and the relationship of IP3R mediated Ca2+ signalling with the pathophysiology of the disease is unclear. It has also been suggested that mitochondrial dysfunction underlies the development of central and diffuse multi-mini-cores, devoid of mitochondrial activity, which is a key pathological consequence of RyR1 mutations. Here we used muscle biopsies of central core and multi-minicore disease patients with RyR1 mutations, as well as cellular and in vivo mouse models of the disease to characterize global cellular and mitochondrial Ca2+ signalling, mitochondrial function and gene expression associated with the disease. We show that RyR1 mutations that lead to the depletion of the channel are associated with increased IP3-mediated nuclear and mitochondrial Ca2+ signals and increased mitochondrial activity. Moreover, western blot and microarray analysis indicated enhanced mitochondrial biogenesis at the transcriptional and protein levels and was reflected in increased mitochondrial DNA content. The phenotype was recapitulated by RYR1 silencing in mouse cellular myotube models. Altogether, these data indicate that remodelling of skeletal muscle Ca2+ signalling following loss of functional RyR1 mediates bioenergetic adaptation.

Rare missense mutations in P2RY11 in narcolepsy with cataplexy.

PubMed

Degn, Matilda; Dauvilliers, Yves; Dreisig, Karin; Lopez, Régis; Pfister, Corinne; Pradervand, Sylvain; Rahbek Kornum, Birgitte; Tafti, Mehdi

2017-06-01

The sleep disorder narcolepsy with cataplexy is characterized by a highly specific loss of hypocretin (orexin) neurons, leading to the hypothesis that the condition is caused by an immune or autoimmune mechanism. All genetic variants associated with narcolepsy are immune-related. Among these are single nucleotide polymorphisms in the P2RY11-EIF3G locus. It is unknown how these genetic variants affect narcolepsy pathogenesis and whether the effect is directly related to P2Y11 signalling or EIF3G function. Exome sequencing in 18 families with at least two affected narcolepsy with cataplexy subjects revealed non-synonymous mutations in the second exon of P2RY11 in two families, and P2RY11 re-sequencing in 250 non-familial cases and 135 healthy control subjects revealed further six different non-synonymous mutations in the second exon of P2RY11 in seven patients. No mutations were found in healthy controls. Six of the eight narcolepsy-associated P2Y11 mutations resulted in significant functional deficits in P2Y11 signalling through both Ca2+ and cAMP signalling pathways. In conclusion, our data show that decreased P2Y11 signalling plays an important role in the development of narcolepsy with cataplexy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EIF3G is associated with narcolepsy across ethnicities.

PubMed

Holm, Anja; Lin, Ling; Faraco, Juliette; Mostafavi, Sara; Battle, Alexis; Zhu, Xiaowei; Levinson, Douglas F; Han, Fang; Gammeltoft, Steen; Jennum, Poul; Mignot, Emmanuel; Kornum, Birgitte R

2015-11-01

Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB1*06:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.*638G>A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy.

Asteroseismology of the δ Scuti star HD 50844

NASA Astrophysics Data System (ADS)

Chen, X. H.; Li, Y.; Lai, X. J.; Wu, T.

2016-09-01

Aims: We aim to probe the internal structure and investigate with asteroseismology for more detailed information on the δ Scuti star HD 50844. Methods: We analyse the observed frequencies of the δ Scuti star HD 50844 and search for possible multiplets, which are based on the rotational splitting law of g-mode. We tried to disentangle the frequency spectra of HD 50844 only by means of rotational splitting. We then compare these with theoretical pulsation modes, which correspond to stellar evolutionary models with various sets of initial metallicity and stellar mass, to find the best-fitting model. Results: There are three multiplets, including two complete triplets and one incomplete quintuplet, in which mode identifications for spherical harmonic degree l and azimuthal number m are unique. The corresponding rotational period of HD 50844 is found to be 2.44 days. The physical parameters of HD 50844 are well limited in a small region by three modes that have been identified as nonradial ones (f11, f22, and f29) and by the fundamental radial mode (f4). Our results show that the three nonradial modes (f11, f22, and f29) are all mixed modes, which mainly represent the property of the helium core. The fundamental radial mode (f4) mainly represents the property of the stellar envelope. To fit these four pulsation modes, both the helium core and the stellar envelope need to be matched to the actual structure of HD 50844. Finally, the mass of the helium core of HD 50844 is estimated to be 0.173 ± 0.004 M⊙ for the first time. The physical parameters of HD 50844 are determined to be M = 1.81 ± 0.01 M⊙, Z = 0.008 ± 0.001. Teff = 7508 ± 125 K, log g = 3.658 ± 0.004, R = 3.300 ± 0.023 R⊙, L = 30.98 ± 2.39 L⊙.

Seismological Modeling of the Delta Scuti Star: CD-24 7599

NASA Astrophysics Data System (ADS)

Bradley, Paul A.; Guzik, Joyce A.

1996-01-01

A major goal of asteroseismology is a better understanding of stellar evolution via ''snapshots'' of many stars of different masses in different evolutionary states. For stars of about 2M(circle dot) near the sequence, b Scuti stars are the usual suspects. There is an ongoing renaissance in theoretical modeling of 6 Scuti stars brought on by improvements in constitutive physics and by a dramatic increase in the number of modes observed. FG Virginis and CD-24' 7599 are two of the best studied objects, and they have 19 and 13 known frequencies, respectively. . We create models using an updated and modified version of the Iben code described by Guzik & Cox that includes either of the two versions of the OPAL opacities . We use the star's observed location on the H-R diagram as a starting point for our seismological modeling. Because there is no evidence for observed t = 3 modes, we only consider l = 0, 1, and 2 modes in our analysis. We take into account rotational splitting (about 5 - 10 (mu)Hz) in our frequency matching. Several observed modes must be rotationally split members of a given mode. CD-24' 7599 is less than halfway through core hydrogen burning, and the modes appear to be a set of consecutive 3rd through 5th overtones of (ital l) = 0 through 2 modes. With only 13 modes, we find satisfactory fits with models between 1.9 and 2.0 M(circle dot) that fall within the observed luminosity and effective temperature range. By contrast, Guzik & Bradley suggest that FG Virginis is over halfway through core hydrogen burning and the best fitting models lie near 1.80 or 2.00 M(circle dot). We see persistent discrepancies in some low frequency modes, which suggests we may need a small amount of core overshoot or a slight change in metallicity to duplicate FG Virginis.

A NEW CENSUS OF THE VARIABLE STAR POPULATION IN THE GLOBULAR CLUSTER NGC 2419

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

Di Criscienzo, M.; Greco, C.; Ripepi, V.

We present B, V, and I CCD light curves for 101 variable stars belonging to the globular cluster NGC 2419, 60 of which are new discoveries, based on data sets obtained at the Telescopio Nazionale Galileo, the Subaru telescope, and the Hubble Space Telescope. The sample includes 75 RR Lyrae stars (38 RRab, 36 RRc, and one RRd), one Population II Cepheid, 12 SX Phoenicis variables, two {delta} Scuti stars, three binary systems, five long-period variables, and three variables of uncertain classification. The pulsation properties of the RR Lyrae variables are close to those of Oosterhoff type II clusters, consistentmore » with the low metal abundance and the cluster horizontal branch morphology, disfavoring (but not totally ruling out) an extragalactic hypothesis for the origin of NGC 2419. The observed properties of RR Lyrae and SX Phoenicis stars are used to estimate the cluster reddening and distance, using a number of different methods. Our final value is {mu}{sub 0} (NGC 2419) = 19.71 {+-} 0.08 mag (D = 87.5 {+-} 3.3 kpc), with E(B - V) = 0.08 {+-} 0.01 mag, [Fe/H] = -2.1 dex on the Zinn and West metallicity scale, and a value of M{sub V} that sets {mu}{sub 0} (LMC) = 18.52 mag. This value is in good agreement with the most recent literature estimates of the distance to NGC 2419.« less

First discovery of a magnetic field in a main-sequence δ Scuti star: the Kepler star HD 188774

NASA Astrophysics Data System (ADS)

Neiner, C.; Lampens, P.

2015-11-01

The Kepler space mission provided a wealth of δ Sct-γ Dor hybrid candidates. While some may be genuine hybrids, others might be misclassified due to the presence of a binary companion or to rotational modulation caused by magnetism and related surface inhomogeneities. In particular, the Kepler δ Sct-γ Dor hybrid candidate HD 188774 shows a few low frequencies in its light and radial velocity curves, whose origin is unclear. In this work, we check for the presence of a magnetic field in HD 188774. We obtained two spectropolarimetric measurements with an Echelle SpectroPolarimetric Device for the Observation of Stars (ESPaDOnS) at Canada-France-Hawaii Telescope. The data were analysed with the least-squares deconvolution (LSD) method. We detected a clear magnetic signature in the Stokes V LSD profiles. The origin of the low frequencies detected in HD 188774 is therefore most probably the rotational modulation of surface spots possibly related to the presence of a magnetic field. Consequently, HD 188774 is not a genuine hybrid δ Sct-γ Dor star, but the first known magnetic main-sequence δ Sct star. This makes it a prime target for future asteroseismic and spot modelling. This result casts new light on the interpretation of the Kepler results for other δ Sct-γ Dor hybrid candidates.

Mutation-Linked Defective Inter-Domain Interactions within Ryanodine Receptor Cause Aberrant Ca2+ Release Leading to Catecholaminergic Polymorphic Ventricular Tachycardia

PubMed Central

Suetomi, Takeshi; Yano, Masafumi; Uchinoumi, Hitoshi; Fukuda, Masakazu; Hino, Akihiro; Ono, Makoto; Xu, Xiaojuan; Tateishi, Hiroki; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Ikeda, Yasuhiho; Yamamoto, Takeshi; Ikemoto, Noriaki; Matsuzaki, Masunori

2011-01-01

Background The molecular mechanism by which catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by single amino acid mutations within the cardiac ryanodine receptor (RyR2) remains elusive. Here, we investigated mutation-induced conformational defects of RyR2 using a knock-in (KI) mouse model expressing the human CPVT-associated RyR2 mutant (S2246L; Serine to Leucine mutation at the residue 2246). Methods and Results All KI mice we examined produced VT after exercise on a treadmill. cAMP-dependent increase in the frequency of Ca2+ sparks was more pronounced in saponin-permeabilized KI cardiomyocytes than in WT cardiomyocytes. Site-directed fluorescent labeling and quartz microbalance assays of the specific binding of DP2246 (a peptide corresponding to the 2232–2266 region: the 2246 domain) showed that DP2246 binds with the K201-binding sequence of RyR2 (1741– 2270). Introduction of S2246L mutation into the DP2246 increased the affinity of peptide binding. Fluorescence quench assays of inter-domain interactions within RyR2 showed that tight interaction of the 2246 domain/K201-binding domain is coupled with domain unzipping of the N-terminal (1-600)/central (2000–2500) domain pair in an allosteric manner. Dantrolene corrected the mutation-caused domain unzipping of the domain switch, and stopped the exercise-induced ventricular tachycardia. Conclusions The CPVT-linked mutation of RyR2, S2246L, causes an abnormally tight local sub-domain/sub-domain interaction within the central domain involving the mutation site, which induces defective interaction between the N-terminal and central domains. This results in an erroneous activation of Ca2+ channel in a diastolic state reflecting on the increased Ca2+ spark frequency, which then leads to lethal arrhythmia. PMID:21768539

Implication of the ryanodine receptor in TRPV4-induced calcium response in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

PubMed

Dahan, Diana; Ducret, Thomas; Quignard, Jean-François; Marthan, Roger; Savineau, Jean-Pierre; Estève, Eric

2012-11-01

There is a growing body of evidence indicating that transient receptor potential (TRP) channels are implicated in calcium signaling and various cellular functions in the pulmonary vasculature. The aim of this study was to investigate the expression, functional role, and coupling to reticulum calcium channels of the type 4 vanilloid TRP subfamily (TRPV4) in the pulmonary artery from both normoxic (Nx) and chronically hypoxic (CH) rats. Activation of TRPV4 with the specific agonist 4α-phorbol-12,13-didecanoate (4α-PDD, 5 μM) increased the intracellular calcium concentration ([Ca(2+)](i)). This effect was significantly reduced by a high concentration of ryanodine (100 μM) or chronic caffeine (5 mM) that blocked ryanodine receptor (RyR) but was insensitive to xestospongin C (10 μM), an inositol trisphosphate receptor antagonist. Inhibition of RyR1 and RyR3 only with 10 μM of dantrolene did not attenuate the 4α-PDD-induced [Ca(2+)](i) increase. Western blotting experiments revealed the expression of TRPV4 and RyR2 with an increase in both receptors in pulmonary arteries from CH rats vs. Nx rats. Accordingly, the 4α-PDD-activated current, measured with patch-clamp technique, was increased in pulmonary artery smooth muscle cells (PASMC) from CH rats vs. Nx rats. 4α-PDD increased isometric tension in artery rings, and this response was also potentiated under chronic hypoxia conditions. 4α-PDD-induced calcium response, current, and contraction were all inhibited by the selective TRPV4 blocker HC-067047. Collectively, our findings provide evidence of the interplay between TRPV4 and RyR2 in the Ca(2+) release mechanism and contraction in PASMC. This study provides new insights onto the complex calcium signaling in PASMC and point out the importance of the TRPV4-RyR2 signaling pathway under hypoxic conditions that may lead to pulmonary hypertension.

Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca²⁺release leading to catecholaminergic polymorphic ventricular tachycardia.

PubMed

Suetomi, Takeshi; Yano, Masafumi; Uchinoumi, Hitoshi; Fukuda, Masakazu; Hino, Akihiro; Ono, Makoto; Xu, Xiaojuan; Tateishi, Hiroki; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Ikeda, Yasuhiro; Yamamoto, Takeshi; Ikemoto, Noriaki; Matsuzaki, Masunori

2011-08-09

The molecular mechanism by which catecholaminergic polymorphic ventricular tachycardia is induced by single amino acid mutations within the cardiac ryanodine receptor (RyR2) remains elusive. In the present study, we investigated mutation-induced conformational defects of RyR2 using a knockin mouse model expressing the human catecholaminergic polymorphic ventricular tachycardia-associated RyR2 mutant (S2246L; serine to leucine mutation at the residue 2246). All knockin mice we examined produced ventricular tachycardia after exercise on a treadmill. cAMP-dependent increase in the frequency of Ca²⁺ sparks was more pronounced in saponin-permeabilized knockin cardiomyocytes than in wild-type cardiomyocytes. Site-directed fluorescent labeling and quartz microbalance assays of the specific binding of DP2246 (a peptide corresponding to the 2232 to 2266 region: the 2246 domain) showed that DP2246 binds with the K201-binding sequence of RyR2 (1741 to 2270). Introduction of S2246L mutation into the DP2246 increased the affinity of peptide binding. Fluorescence quench assays of interdomain interactions within RyR2 showed that tight interaction of the 2246 domain/K201-binding domain is coupled with domain unzipping of the N-terminal (1 to 600)/central (2000 to 2500) domain pair in an allosteric manner. Dantrolene corrected the mutation-caused domain unzipping of the domain switch and stopped the exercise-induced ventricular tachycardia. The catecholaminergic polymorphic ventricular tachycardia-linked mutation of RyR2, S2246L, causes an abnormally tight local subdomain-subdomain interaction within the central domain involving the mutation site, which induces defective interaction between the N-terminal and central domains. This results in an erroneous activation of Ca²⁺ channel in a diastolic state reflecting on the increased Ca²⁺ spark frequency, which then leads to lethal arrhythmia.

Postoperative long-term evaluation of interposition reconstruction compared with Roux-en-Y after total gastrectomy in gastric cancer: prospective randomized controlled trial.

PubMed

Ishigami, Sumiya; Natsugoe, Shoji; Hokita, Shuichi; Aoki, Teruaki; Kashiwagi, Hideyuki; Hirakawa, Kosei; Sawada, Tetsuji; Yamamura, Yoshitaka; Itoh, Seiji; Hirata, Koichi; Ohta, Keiichiro; Mafune, Kenichi; Nakane, Yasushi; Kanda, Tatsuo; Furukawa, Hiroshi; Sasaki, Iwao; Kubota, Tetsuro; Kitajima, Masaki; Aikou, Takashi

2011-09-01

The postoperative clinical superiority of the interposition of jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total gastrectomy has not been clarified. Postoperative quality of life (QOL) was evaluated between the 2 methods by a multi-institutional prospective randomized trial. A total of 103 patients with gastric cancer were prospectively randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after total gastrectomy. They were stratified by sex, age, institute, histology, and degree of lymph node dissection. Postoperatively, body mass index (BMI) and nutritional conditions were measured serially, and QOL and postoperative squalor scores were evaluated at 3, 12, and 60 months and compared between the 2 groups. After removing patients who did not complete the follow-up survey or censured cases, 24 patients in the RY group and 18 patients in the INT group were clinically available and their postoperative status was assessed. QOL scores were increased and complication scores were improved in the postoperative periods (P < .01). Postoperative BMI significantly deteriorated compared with preoperative BMI in each group. The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group (P < .01). However, there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups. The nutritional condition in the INT group was nearly the same as that in the RY group. Although our patient sample was small and patients who did not complete the follow-up survey were present, we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery. The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy. Copyright © 2011. Published by Elsevier Inc.

Characterization of ryanodine receptor and Ca2+-ATPase isoforms in the thermogenic heater organ of blue marlin (Makaira nigricans).

PubMed

Morrissette, Jeffery M; Franck, Jens P G; Block, Barbara A

2003-03-01

A thermogenic organ is found beneath the brain of billfishes (Istiophoridae), swordfish (Xiphiidae) and the butterfly mackerel (Scombridae). The heater organ has been shown to warm the brain and eyes up to 14 degrees C above ambient water temperature. Heater cells are derived from extraocular muscle fibers and express a modified muscle phenotype with an extensive transverse-tubule (T-tubule) network and sarcoplasmic reticulum (SR) enriched in Ca(2+)-ATPase (SERCA) pumps and ryanodine receptors (RyRs). Heater cells have a high mitochondria content but have lost most of the contractile myofilaments. Thermogenesis has been hypothesized to be associated with release and reuptake of Ca(2+). In this study, Ca(2+) fluxes in heater SR vesicles derived from blue marlin (Makaira nigricans) were measured using fura-2 fluorescence. Upon the addition of MgATP, heater SR vesicles rapidly sequestered Ca(2+). Uptake of Ca(2+) was thapsigargin sensitive, and maximum loading ranged between 0.8 micro mol Ca(2+) mg(-1) protein and 1.0 micro mol Ca(2+) mg(-1) protein. Upon the addition of 10 mmol l(-1) caffeine or 350 micro mol l(-1) ryanodine, heater SR vesicles released only a small fraction of the loaded Ca(2+). However, ryanodine could elicit a much larger Ca(2+) release event when the activity of the SERCA pumps was reduced. RNase protection assays revealed that heater tissue expresses an RyR isoform that is also expressed in fish slow-twitch skeletal muscle but is distinct from the RyR expressed in fish fast-twitch skeletal muscle. The heater and slow-twitch muscle RyR isoform has unique physiological properties. In the presence of adenine nucleotides, this RyR remains open even though cytoplasmic Ca(2+) is elevated, a condition that normally closes RyRs. The fast Ca(2+) sequestration by the heater SR, coupled with a physiologically unique RyR, is hypothesized to promote Ca(2+) cycling, ATP turnover and heat generation. A branch of the oculomotor nerve innervates heater organs, and, in this paper, we demonstrate that heater cells contain large 'endplate-like' clusters of acetylcholine receptors that appear to provide a mechanism for nervous control of thermogenesis.

Characterization of the patterns of polymorphism in a [open quotes]cryptic repeat[close quotes] reveals a novel type of hypervariable sequence

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

Jacobson, D.P.; Schmeling, P.; Sommer, S.S.

Alternating purine and pyrimidine repeats (RY(i)) are an abundant source of polymorphism. The subset with long tandem repeats of GT or AC (GT(i)) have been studied extensively, but cryptic RY(i) (i.e., no single tandem repeat predominates) have received little attention. The factor IX gene has a polymorphic cryptic RY(i) of 142-216 bp. Previously, there were four known polymorphic alleles, of the form AB, A[sub 2]B, A[sub 2]B[sub 2], and A[sub 3]B[sub 2], where A = (GT)(AC)[sub 3](AT)[sub 3](GT)(AT)[sub 4] and B = A with an additional 3' AT dinucleotide. To further characterize this locus, the authors examined more than 1,700more » additional human chromosomes and determined the sequences of the homologous sites in orangutans and chimpanzees. The novel alleles found in humans expand the repertoire of A/B alleles to A[sub 0-4]B[sub 1] and A[sub 1-3]B[sub 2]. The A[sub n]B[sub 2] series are abundant in Caucasians but are absent in blacks and Asians. Conversely, the A[sub 0]B[sub 1] allele is common in blacks but is not found in more than 1,700 Caucasian chromosomes. The data are compatible with a model in which recombination is more frequent than polymerase slippage at this locus. In orangutans, the RY(i) is present, but the sequence is markedly different. An A/B-type of pattern was discerned in which B differs from A by an additional six (AT) dinucleotides at the 3' end. In chimpanzees, the size of the RY(i) locus was greatly expanded, and the sequence showed a novel pattern of hypervariability in which there are many tandem repeats of the form (GT)[sub n](AC)[sub 0](AT)[sub p](GT)[sub q](AT)[sub s], where n, o, p, q, and s are different integers. The sequences of the factor IX intron 1 cryptic RY(i) in three primates provide perspective on the range of possible patterns of polymorphism. Analysis of the patterns suggests how the RY(i) can be conserved during evolution, while the precise sequence varies. 25 refs., 5 figs., 3 tabs.« less

Geographic spread, genetics and functional characteristics of ryanodine receptor based target-site resistance to diamide insecticides in diamondback moth, Plutella xylostella.

PubMed

Steinbach, Denise; Gutbrod, Oliver; Lümmen, Peter; Matthiesen, Svend; Schorn, Corinna; Nauen, Ralf

2015-08-01

Anthranilic diamides and flubendiamide belong to a new chemical class of insecticides acting as conformation sensitive activators of the insect ryanodine receptor (RyR). These compounds control a diverse range of different herbivorous insects including diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae), a notorious global pest on cruciferous crops, which recently developed resistance due to target-site mutations located in the trans-membrane domain of the Plutella RyR. In the present study we further investigated the genetics and functional implications of a RyR G4946E target-site mutation we recently identified in a Philippine diamondback moth strain (Sudlon). Strain Sudlon is homozygous for the G4946E mutation and has been maintained under laboratory conditions without selection pressure for almost four years, and still exhibit stable resistance ratios of >2000-fold to all commercial diamides. Its F1 progeny resulting from reciprocal crosses with a susceptible strain (BCS-S) revealed no maternal effects and a diamide susceptible phenotype, suggesting an autosomally almost recessive mode of inheritance. Subsequent back-crosses indicate a near monogenic nature of the diamide resistance in strain Sudlon. Radioligand binding studies with Plutella thoracic microsomal membrane preparations provided direct evidence for the dramatic functional implications of the RyR G4946E mutation on both diamide specific binding and its concentration dependent modulation of [(3)H]ryanodine binding. Computational modelling based on a cryo-EM structure of rabbit RyR1 suggests that Plutella G4946E is located in trans-membrane helix S4 close to S4-S5 linker domain supposed to be involved in the modulation of the voltage sensor, and another recently described mutation, I4790M in helix S2 approx. 13 Å opposite of G4946E. Genotyping by pyrosequencing revealed the presence of the RyR G4946E mutation in larvae collected in 2013/14 in regions of ten different countries where diamide insecticides largely failed to control diamondback moth populations. Thus, our study highlights the global importance of the G4946E RyR target-site mutation, which as a mechanism on its own, confers high-level resistance to diamide insecticides in diamondback moth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts

PubMed Central

Cooper, Leroy L; Li, Weiyan; Lu, Yichun; Centracchio, Jason; Terentyeva, Radmila; Koren, Gideon; Terentyev, Dmitry

2013-01-01

Ageing is associated with a blunted response to sympathetic stimulation and an increased risk of arrhythmia and sudden cardiac death. Aberrant calcium (Ca2+) handling is an important contributor to the electrical and contractile dysfunction associated with ageing. Yet, the specific molecular mechanisms underlying abnormal Ca2+ handling in ageing heart remain poorly understood. In this study, we used ventricular myocytes isolated from young (5–9 months) and old (4–6 years) rabbit hearts to test the hypothesis that changes in Ca2+ homeostasis are caused by post-translational modification of ryanodine receptors (RyRs) by mitochondria-derived reactive oxygen species (ROS) generated in the ageing heart. Changes in parameters of Ca2+ handling were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) Ca2+ dynamics in intact and permeabilized ventricular myocytes using confocal microscopy. We also measured age-related changes in ROS production and mitochondria membrane potential using a ROS-sensitive dye and a mitochondrial voltage-sensitive fluorescent indicator, respectively. In permeablized myocytes, ageing did not change SERCA activity and spark frequency but decreased spark amplitude and SR Ca2+ load suggesting increased RyR activity. Treatment with the antioxidant dithiothreitol reduced RyR-mediated SR Ca2+ leak in permeabilized myocytes from old rabbit hearts to the level comparable to young. Moreover, myocytes from old rabbits had more depolarized mitochondria membrane potential and increased rate of ROS production. Under β-adrenergic stimulation, Ca2+ transient amplitude, SR Ca2+ load, and latency of pro-arrhythmic spontaneous Ca2+ waves (SCWs) were decreased while RyR-mediated SR Ca2+ leak was increased in cardiomyocytes from old rabbits. Additionally, with β-adrenergic stimulation, scavenging of mitochondrial ROS in myocytes from old rabbit hearts restored redox status of RyRs, which reduced SR Ca2+ leak, ablated most SCWs, and increased latency to levels comparable to young. These data indicate that an age-associated increase of ROS production by mitochondria leads to the thiol-oxidation of RyRs, which underlies the hyperactivity of RyRs and thereby shortened refractoriness of Ca2+ release in cardiomyocytes from the ageing heart. This mechanism probably plays an important role in the increased incidence of arrhythmia and sudden death in the ageing population. PMID:24042501

Reconnecting Youth: A Peer Group Approach to Building Life Skills.

ERIC Educational Resources Information Center

Eggert, Leona L.; Nicholas, Liela J.; Owen, Linda M.

The Reconnecting Youth (RY) program offers a carefully designed, research-validated model for building strength and competence in at-risk students, transforming risk into resilience. This manual was written to assist group leaders in implementing the RY program. The overall purpose of the program is to reach high-risk youth, who are on a potential…

Twilight Musings Concerning the Gamma Doradus Phenomenon

NASA Astrophysics Data System (ADS)

Kaye, A. B.; Zerbi, F. M.

1997-07-01

In this contribution, we intend to address some of the points in the article entitled ``Night Thoughts on Slowly Variable F-Type Stars'' by Gautschy and Loeffler in the Delta Scuti Newsletter, issue 10 (1996). We present these points as direct results of the conference ``A Half-Century of Stellar Pulsation'' at Los Alamos National Laboratory in June 1997.

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise

PubMed Central

Place, Nicolas; Ivarsson, Niklas; Venckunas, Tomas; Neyroud, Daria; Brazaitis, Marius; Cheng, Arthur J.; Ochala, Julien; Kamandulis, Sigitas; Girard, Sebastien; Volungevičius, Gintautas; Paužas, Henrikas; Mekideche, Abdelhafid; Kayser, Bengt; Martinez-Redondo, Vicente; Bruton, Joseph; Truffert, Andre; Lanner, Johanna T.; Skurvydas, Albertas; Westerblad, Håkan

2015-01-01

High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca2+ leak at rest, and depressed force production due to impaired SR Ca2+ release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca2+-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group. PMID:26575622

Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

PubMed

Place, Nicolas; Ivarsson, Niklas; Venckunas, Tomas; Neyroud, Daria; Brazaitis, Marius; Cheng, Arthur J; Ochala, Julien; Kamandulis, Sigitas; Girard, Sebastien; Volungevičius, Gintautas; Paužas, Henrikas; Mekideche, Abdelhafid; Kayser, Bengt; Martinez-Redondo, Vicente; Ruas, Jorge L; Bruton, Joseph; Truffert, Andre; Lanner, Johanna T; Skurvydas, Albertas; Westerblad, Håkan

2015-12-15

High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group.

Effects of Cloud Particles on Remote Sensing from Space in the 10-Micrometer Infrared Region.

DTIC Science & Technology

1977-01-01

ayers , that is , a plane-parallel atmosphere wi th infinite hori zontal extent . As a matter of fact, this is how the planeta ry atmosphere is being...Remote Probin g of the Atmosphe re, 1973. 43 . Hansen , J. E. and L. D. Travis , 1974 , “Light Scattering in Planeta ry • Atmospheres ,” Goddard

The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes.

PubMed

Chen, Xudong; Feng, Yundi; Huo, Yunlong; Tan, Wenchang

2018-01-01

Ca 2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca 2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca 2+ waves. The model successfully reproduces Ca 2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of "spark-diffusion-quark-spark" is put forward. It is found that rogue RyRs greatly increase the initiation of Ca 2+ sparks, further contribute to the formation and propagation of Ca 2+ waves when the free Ca 2+ concentration in JSR lumen ([Ca 2+ ] lumen ) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca 2+ waves with [Ca 2+ ] lumen . In addition, more CRUs of rogue RyRs and Ca 2+ release from rogue RyRs result in higher velocity and amplitude of Ca 2+ waves. Distance between CRUs significantly affects the velocity of Ca 2+ waves, but not the amplitude. This work could improve understanding the mechanism of Ca 2+ waves in cardiac myocytes.

The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes

PubMed Central

Chen, Xudong; Feng, Yundi; Huo, Yunlong; Tan, Wenchang

2018-01-01

Ca2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca2+ waves. The model successfully reproduces Ca2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of “spark-diffusion-quark-spark” is put forward. It is found that rogue RyRs greatly increase the initiation of Ca2+ sparks, further contribute to the formation and propagation of Ca2+ waves when the free Ca2+ concentration in JSR lumen ([Ca2+]lumen) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca2+ waves with [Ca2+]lumen. In addition, more CRUs of rogue RyRs and Ca2+ release from rogue RyRs result in higher velocity and amplitude of Ca2+ waves. Distance between CRUs significantly affects the velocity of Ca2+ waves, but not the amplitude. This work could improve understanding the mechanism of Ca2+ waves in cardiac myocytes. PMID:29755362

Examples of seismic modelling

NASA Astrophysics Data System (ADS)

Pamyatnykh, A. A.

2008-12-01

Findings of a few recent asteroseismic studies of the main sequence pulsating stars, as per- formed in Wojciech Dziembowski’s group in Warsaw and in Michel Breger’s group in Vienna, are briefly presented and discussed. The selected objects are three hybrid pulsators ν Eridani, 12 Lacertae and γ Pegasi, which show both β Cephei and SPB type modes, and the δ Scuti type star 44 Tauri.

Discovery of multiple pulsations in the new δ Scuti star HD 92277: Asteroseismology from Dome A, Antarctica

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

Zong, Weikai; Fu, Jian-Ning; Niu, Jia-Shu

We report the discovery of low-amplitude oscillations in the star HD 92277 from long, continuous observations in the r and g bands using the CSTAR telescopes in Antarctica. A total of more than 1950 hours of high-quality light curves were used to categorize HD 92277 as a new member of the δ Scuti class. We have detected 21 (20 frequencies are independent and one is the linear combination) and 14 (13 frequencies are independent and one is the linear combination) pulsation frequencies in the r and g bands, respectively, indicating a multi-periodic pulsation behavior. The primary frequency f{sub 1} =more » 10.810 days{sup −1} corresponds to a period of 0.0925 days and is an l = 1 mode. We estimate a B − V index of 0.39 and derive an effective temperature of 6800 K for HD 92277. We conclude that long, continuous and uninterrupted time-series photometry can be performed from Dome A, Antarctica, and that this is especially valuable for asteroseismology where multi-color observations (often not available from space-based telescopes) assist with mode identification.« less

Pulsations of the High-Amplitude δ Scuti star YZ Bootis

NASA Astrophysics Data System (ADS)

Yang, Tao-Zhi; Esamdin, Ali; Fu, Jian-Ning; Niu, Hu-Biao; Feng, Guo-Jie; Song, Fang-Fang; Liu, Jin-Zhong; Ma, Lu

2018-01-01

We present a study on pulsations of the high-amplitude δ Scuti star YZ Boo based on photometric observations in Johnson V and R bands with both the Nanshan 1-m telescope of Xinjiang AstronomicalObservatory (XAO) and the Xinglong 85-cmtelescope of NationalAstronomical Observatories, Chinese Academy of Sciences (NAOC). Fourier analysis of the light curves reveals the fundamental radial mode and its five harmonics, with the fourth and fifth being newly detected. Thirty-nine new times of maximum light are determined from the light curves, and combined with those in the literature, we construct the O ‑ C diagram, derive a new ephemeris and determine a new value for the updated period of 0.104091579(2). In addition, the O ‑ C diagram reveals an increasing rate of period change for YZ Boo. Theoretical models are calculated and constrained with the observationally determined parameters of YZ Boo. The mass and age of YZ Boo are hence derived as M = 1.61±0.05 M ⊙ and age = (1.44±0.14)×109 yr, respectively.With both the frequency of the fundamental radial mode and the rate of period change, YZ Boo is located at the post main sequence stage.

The Enumeration Structure of 爾雅 Ěryǎ's "Semantic Lists"

NASA Astrophysics Data System (ADS)

Teboul (戴明德), Michel

Modern linguistic enumeration theory is applied to a study of 爾雅 Ěryǎ's Semantic Lists, leading to an in-depth analysis of the work's first three sections without any recourse to the traditional methods of Chinese classical philology. It is hoped that an extension of the same method can lead to a better understanding of the remaining 16 sections.

[Ottoman pharmacist Pierre Apéry and his scientifical publications].

PubMed

Nicolas, Michèle

2006-01-01

Pierre Apéry, owner of a laboratory and one of the most famous pharmacy in Istanbul, is a model of life quite devoted to his business. His publications (end of 19th/beginning of 20th century), which plaid a major role in the formation and the dissemination of knowledge about health, are a precious testimony about pharmacy and medicine in the Ottoman Empire.

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

PubMed

Roston, Thomas M; Yuchi, Zhiguang; Kannankeril, Prince J; Hathaway, Julie; Vinocur, Jeffrey M; Etheridge, Susan P; Potts, James E; Maginot, Kathleen R; Salerno, Jack C; Cohen, Mitchell I; Hamilton, Robert M; Pflaumer, Andreas; Mohammed, Saira; Kimlicka, Lynn; Kanter, Ronald J; LaPage, Martin J; Collins, Kathryn K; Gebauer, Roman A; Temple, Joel D; Batra, Anjan S; Erickson, Christopher; Miszczak-Knecht, Maria; Kubuš, Peter; Bar-Cohen, Yaniv; Kantoch, Michal; Thomas, Vincent C; Hessling, Gabriele; Anderson, Chris; Young, Ming-Lon; Choi, Sally H J; Cabrera Ortega, Michel; Lau, Yung R; Johnsrude, Christopher L; Fournier, Anne; Van Petegem, Filip; Sanatani, Shubhayan

2018-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Sorcin modulation of Ca2+ sparks in rat vascular smooth muscle cells

PubMed Central

Rueda, Angélica; Song, Ming; Toro, Ligia; Stefani, Enrico; Valdivia, Héctor H

2006-01-01

Spontaneous, local Ca2+ release events or Ca2+ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca2+-binding protein that associates with cardiac RyRs and quickly stops Ca2+ release in the heart, provides a potential mechanism to modulate Ca2+ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca2+ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca2+-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca2+ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca2+ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca2+ spark properties. Perfusion of 2 μm sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca2+ sparks, demonstrating that sorcin effectively regulates Ca2+ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle. PMID:16931553

Amino acid residues 489-503 of dihydropyridine receptor (DHPR) β1a subunit are critical for structural communication between the skeletal muscle DHPR complex and type 1 ryanodine receptor.

PubMed

Eltit, Jose M; Franzini-Armstrong, Clara; Perez, Claudio F

2014-12-26

The β1a subunit is a cytoplasmic component of the dihydropyridine receptor (DHPR) complex that plays an essential role in skeletal muscle excitation-contraction (EC) coupling. Here we investigate the role of the C-terminal end of this auxiliary subunit in the functional and structural communication between the DHPR and the Ca(2+) release channel (RyR1). Progressive truncation of the β1a C terminus showed that deletion of amino acid residues Gln(489) to Trp(503) resulted in a loss of depolarization-induced Ca(2+) release, a severe reduction of L-type Ca(2+) currents, and a lack of tetrad formation as evaluated by freeze-fracture analysis. However, deletion of this domain did not affect expression/targeting or density (Qmax) of the DHPR-α1S subunit to the plasma membrane. Within this motif, triple alanine substitution of residues Leu(496), Leu(500), and Trp(503), which are thought to mediate direct β1a-RyR1 interactions, weakened EC coupling but did not replicate the truncated phenotype. Therefore, these data demonstrate that an amino acid segment encompassing sequence (489)QVQVLTSLRRNLSFW(503) of β1a contains critical determinant(s) for the physical link of DHPR and RyR1, further confirming a direct correspondence between DHPR positioning and DHPR/RyR functional interactions. In addition, our data strongly suggest that the motif Leu(496)-Leu(500)-Trp(503) within the β1a C-terminal tail plays a nonessential role in the bidirectional DHPR/RyR1 signaling that supports skeletal-type EC coupling. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Resistance to Diamide Insecticides in Plutella xylostella (Lepidoptera: Plutellidae): Comparison Between Lab-Selected Strains and Field-Collected Populations.

PubMed

Qin, Chao; Wang, Cheng-Hua; Wang, Ying-Ying; Sun, Shi-Qing; Wang, Huan-Huan; Xue, Chao-Bin

2018-04-02

Diamondback moth, Plutella xylostella (L.; Lepidoptera: Plutellidae), is an important pest of crucifers worldwide. The extensive use of diamide insecticides has led to P. xylostella resistance and this presents a serious threat to vegetable production. We selected chlorantraniliprole (Rf) and flubendiamide (Rh) resistance strains of P. xylostella with resistance ratios of 684.54-fold and 677.25-fold, respectively. The Rf and Rh strains underwent 46 and 36 generations of lab-selection for resistance, respectively. Low cross resistance of Rh to cyantraniliprole was found. Cross resistance to chlorfenapyr, tebufenozid, and indoxacarb was not found in Rf and Rh strains. The P. xylostella ryanodine receptor gene (PxRyR) transcripts level in the Rf and Rh strains was up-regulated. Except for Rf34 and Rh36, PxRyR expression in all generations of Rf and Rh selection gradually increased with increasing resistance. Two resistant populations were field-collected from Guangzhou Baiyun (Rb) and Zengcheng (Rz) and propagated for several generations without exposure to any pesticide had higher PxRyR expression than the susceptible strain (S). In the S strain, PxRyR expression was not related to the resistance ratio. Gene sequencing found that the RyR 4946 gene site was glycine (G) in the S, Rf, and Rh strains, and was glutamate (E) with 70% and 80% frequency in the Rb and Rz populations, respectively. The 4946 gene site was substituted by valine (V) with the frequency of 30% and 20% in Rb and Rz populations, respectively. These results increase the understanding of the mechanisms of diamide insecticide resistance in P. xylostella.

Ground state energy of electrons in a static point-ion lattice

NASA Technical Reports Server (NTRS)

Styer, D. F.; Ashcroft, N. W.

1983-01-01

The ground state energy of a neutral collection of protons and electrons was investigated under the assumption that in the ground state configuration, static protons occupy the sites of a rigid Bravais lattice. The Wigner-Seitz method was used in conjunction with three postulated potentials: bare Coulomb, Thomas-Fermi screening, and screening by a uniform bare background charge. Within these approximations, the exact band-minimum energy and wave functions are derived. For each of the three potentials, the approximate minimum ground state energy per proton (relative to isolated electrons and protons) is, respectively, -1.078 Ry, -1.038 Ry, and -1.052 Ry. These three minima all fall at a density of about 0.60 gm/cu cm, which is thus an approximate lower bound on the density of metallic hydrogen at its transition pressure.

Type 1 Inositol (1,4,5)-Trisphosphate Receptor Activates Ryanodine Receptor 1 to Mediate Calcium Spark Signaling in Adult Mammalian Skeletal Muscle*♦

PubMed Central

Tjondrokoesoemo, Andoria; Li, Na; Lin, Pei-Hui; Pan, Zui; Ferrante, Christopher J.; Shirokova, Natalia; Brotto, Marco; Weisleder, Noah; Ma, Jianjie

2013-01-01

Functional coupling between inositol (1,4,5)-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) represents a critical component of intracellular Ca2+ signaling in many excitable cells; however, the role of this mechanism in skeletal muscle remains elusive. In skeletal muscle, RyR-mediated Ca2+ sparks are suppressed in resting conditions, whereas application of transient osmotic stress can trigger activation of Ca2+ sparks that are restricted to the periphery of the fiber. Here we show that onset of these spatially confined Ca2+ sparks involves interaction between activation of IP3R and RyR near the sarcolemmal membrane. Pharmacological prevention of IP3 production or inhibition of IP3R channel activity abolishes stress-induced Ca2+ sparks in skeletal muscle. Although genetic ablation of the type 2 IP3R does not appear to affect Ca2+ sparks in skeletal muscle, specific silencing of the type 1 IP3R leads to ablation of stress-induced Ca2+ sparks. Our data indicate that membrane-delimited signaling involving cross-talk between IP3R1 and RyR1 contributes to Ca2+ spark activation in skeletal muscle. PMID:23223241

Recombination Can Initiate and Terminate at a Large Number of Sites within the Rosy Locus of Drosophila Melanogaster

PubMed Central

Clark, S. H.; Hilliker, A. J.; Chovnick, A.

1988-01-01

This report presents the results of a recombination experiment designed to question the existence of special sites for the initiation or termination of a recombination heteroduplex within the region of the rosy locus. Intragenic recombination events were monitored between two physically separated rosy mutant alleles ry(301) and ry(2) utilizing DNA restriction site polymorphisms as genetic markers. Both ry(301) and ry(2) are known from previous studies to be associated with gene conversion frequencies an order of magnitude lower than single site mutations. The mutations are associated with large, well defined insertions located as internal sites within the locus in prior intragenic mapping studies. On the molecular map, they represent large insertions approximately 2.7 kb apart in the second and third exons, respectively, of the XDH coding region. The present study monitors intragenic recombination in a mutant heterozygous genotype in which DNA homology is disrupted by these large discontinuities, greater than the region of DNA homology and flanking both sides of the locus. If initiation/or termination requires separate sites at either end of the locus, then intragenic recombination within the rosy locus of the heterozygote should be eliminated. Contrary to expectation, significant recombination between these sites is seen. PMID:2834266

Paraneoplastic myasthenia gravis: immunological and clinical aspects.

PubMed

Skeie, G O; Romi, F

2008-10-01

Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make-up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late-onset MG (age >or= 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient's immunological profile. Paraneoplastic MG causes a distinctive non-limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre-thymectomy plasmapheresis or iv-IgG should be considered in these patients to minimize post-thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non-paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR-related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.

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

Cacciari, C.; Clementini, G.

Attention is given to the folowing topics: population I and II variable stars; LP variables, the sun, and mass determination; and predegenerate and degenerate variables. Particular papers are presented on alternative evolutionary approaches to the absolute magnitude of the RR Lyrae variables; the evolution of the Cepheid stars; nonradial pulsations in rapidly rotating Delta Scuti stars; dynamical models of dust shells around Mira variables; and pulsations of central stars of planetary nebulae.

Variable Stars in Large Magellanic Cloud Globular Clusters. II. NGC 1786

NASA Astrophysics Data System (ADS)

Kuehn, Charles A.; Smith, Horace A.; Catelan, Márcio; Pritzl, Barton J.; De Lee, Nathan; Borissova, Jura

2012-12-01

This is the second in a series of papers studying the variable stars in Large Magellanic Cloud globular clusters. The primary goal of this series is to study how RR Lyrae stars in Oosterhoff-intermediate systems compare to their counterparts in Oosterhoff I/II systems. In this paper, we present the results of our new time-series B-V photometric study of the globular cluster NGC 1786. A total of 65 variable stars were identified in our field of view. These variables include 53 RR Lyraes (27 RRab, 18 RRc, and 8 RRd), 3 classical Cepheids, 1 Type II Cepheid, 1 Anomalous Cepheid, 2 eclipsing binaries, 3 Delta Scuti/SX Phoenicis variables, and 2 variables of undetermined type. Photometric parameters for these variables are presented. We present physical properties for some of the RR Lyrae stars, derived from Fourier analysis of their light curves. We discuss several different indicators of Oosterhoff type which indicate that the Oosterhoff classification of NGC 1786 is not as clear cut as what is seen in most globular clusters. Based on observations taken with the SMARTS 1.3 m telescope operated by the SMARTS Consortium and observations taken at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

Muscle Dysfunction in Androgen Deprivation: Role of Ryanodine Receptor

DTIC Science & Technology

2016-11-01

undergoing ORX have reduced muscle specific force due to calcium leak through RyR1, which is caused by high levels of TGFβ released from the bone during... leak could be causing long-term effects, such as decreased muscle mass, body weight and forelimb grip strength. 15. SUBJECT TERMS Prostate Cancer...calcium leak and contractile dysfunction in chronic muscle fatigue, heart failure and muscular dystrophy (13-16). RyR1 is the skeletal muscle

Proteins as Supramolecular Building Blocks for Responsive Materials and Nanodevices

DTIC Science & Technology

2015-12-20

Wojciechowski, Han Yue Zheng, James E. A. Webb, Céline Valéry, Pall Thordarson , Natalie O. V. Plank, Juliet A. Gerrard, Justin M. Hodgkiss. Functional...materials: Eakins GL, Pandey R, Wojciechowski JP, Zheng  HY, Webb  JEA, Valéry C,  Thordarson  P, Plank NOV, Gerrard  JA, Hodgkiss  JM. 2015:  Functional

Magnetic and thermal property studies of RCrTeO6 (R=trivalent lanthanides) with layered honeycomb sublattices

NASA Astrophysics Data System (ADS)

Narsinga Rao, G.; Sankar, R.; Panneer Muthuselvam, I.; Chou, F. C.

2014-12-01

We have investigated the magnetic ordering of the RCrTeO6 (R=Y, La, Tb and Er) samples comprising Cr3+ (S=3/2). The X-ray diffraction structure analysis revealed that all samples are a hexagonal structure with the space group P 3bar. The magnetic susceptibility χ(T) and heat capacity CP(T) measurement results reveal that both short range and long range antiferromagnetic (AFM) orderings exist in non-magnetic rare earth R=Y and La compounds. For isostructural compounds of R=Tb and Er, CP(T) curves show long range ordering at the same temperature as non-magnetic R=Y, which indicates that the super-super exchange of Cr spins dominates. For R elements of Tb and Er with large spins sitting between honeycomb sublattices composed of CrO6-TeO6 octahedra, the two sublattices of R and Cr appear to be independently magnetic.

Gain of function AMP-activated protein kinase γ3 mutation (AMPKγ3R200Q) in pig muscle increases glycogen storage regardless of AMPK activation.

PubMed

Scheffler, Tracy L; Park, Sungkwon; Roach, Peter J; Gerrard, David E

2016-06-01

Chronic activation of AMP-activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1(R615C)) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPKγ3 subunit (AMPKγ3(R200Q)); this may decrease the glycogen storage capacity of AMPKγ3(R200Q) + RyR1(R615C) muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPKγ3(R200Q) and AMPK activation contribute to glycogen storage and metabolism in muscle. We selected and bred pigs in order to generate offspring with naturally occurring AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q) + RyR1(R615C) mutations, and also retained wild-type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1(R615C), AMPKγ3(R200Q) increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6-phosphate (G6P) was decreased in AMPKγ3(R200Q) relative to all other genotypes, whereas both AMPKγ3(R200Q) and AMPKγ3(R200Q) + RyR1(R615C) muscle exhibited increased GS activity with G6P. Increased activity of GS with G6P was not associated with increased abundance of GS or hexokinase 2. However, AMPKγ3(R200Q) enhanced UDP-glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate-limiting enzyme for glycogen synthesis, our model suggests that UGP2 plays an important role in increasing flux to glycogen synthase. Moreover, we have shown that the capacity for glycogen storage is more closely related to the AMPKγ3(R200Q) mutation than activity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Experimental Studies on Pressure and Temperature Effects on Deep Dea Organisms.

DTIC Science & Technology

1980-02-28

SUPPLEMENTARY NOTES Research published in two papers: (a) George, R.Y. 1979. What Adaptive Strategies Promote Immig ration and Speciation in Deep Sea...Environment. Sarsia 64(1-2):61-65. (b) George, R.Y. 1979. Behavorial and 4etabolic Adaptations o Polar and Deep Sea Crustaceans. Bull. Biol. Soc. W ch #3...pages 283-296. 19. KE WORDS (Continue on reverse side If noeemy and Identify by block nuimber) Pressure adaptation , temperature-pressure interaction

Clinical usefulness of a short-type, prototype single-balloon enteroscope for endoscopic retrograde cholangiopancreatography in patients with altered gastrointestinal anatomy: preliminary experiences.

PubMed

Kawamura, Takuji; Uno, Koji; Suzuki, Azumi; Mandai, Koichiro; Nakase, Kojiro; Tanaka, Kiyohito; Yasuda, Kenjiro

2015-01-01

A limited number of endoscopic retrograde cholangiopancreatography (ERCP) accessories are compatible with the conventional single-balloon enteroscope (SBE) because of the latter's dimensions. The aim of the present study was to assess the utility of a prototype SBE that has a shorter working length and a wider channel than the conventional SBE. ERCP procedures carried out between January 2012 and July 2013 using the short SBE prototype were reconstructions such as Billroth II (B-II), post-gastrectomy with Roux-en-Y (RY-G), and post-choledochojejunostomy with Roux-en-Y (RY-CJ). We retrospectively analyzed the rate of reaching the blind end of the intestine, the diagnostic success rate, the interventional success rate, and the frequency of related complications. Twenty-seven ERCP procedures on 18 patients analyzed comprised two B-II, 15 RY-G, and 10 RY-CJ reconstructions. With a mean procedure time of 56 min (range 40-150 min), the rate of reaching the blind end, the diagnostic success rate, and the interventional success rate were 24/27 (89%), 20/27 (74%), and 19/27 (70%), respectively. There were no major ERCP-related complications in any patient. The prototype short-type SBE appears safe and effective for use in ERCP, and is compatible with conventional endoscopy accessories. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Functional analysis of a point mutation in the ryanodine receptor of Plutella xylostella (L.) associated with resistance to chlorantraniliprole.

PubMed

Guo, Lei; Wang, Yi; Zhou, Xuguo; Li, Zhenyu; Liu, Shangzhong; Pei, Liang; Gao, Xiwu

2014-07-01

The diamondback moth, Plutella xylostella (L.) has developed extremely high resistance to chlorantraniliprole and other diamide insecticides in the field. A glycine to glutamic acid substitution (G4946E) in the P. xylostella ryanodine receptor (PxRyR) has been found in two resistant populations collected in Thailand and Philippines and was considered associated with the diamide insecticides resistance but no experimental evidence was provided. The present study aimed to clarify the function of the reported mutation in chlorantraniliprole resistance in P. xylostella. We identified the same mutation (G4946E) in PxRyR from four field collected chlorantraniliprole resistant populations of Plutella xylostella in China. Most importantly, we found that the frequency of the G4946E mutation is significantly correlated to the chlorantraniliprole resistance ratios in P. xylostella (R(2)  = 0.82, P = 0.0003). Ligand binding assays showed that the binding affinities of the PxRyR to the chlorantraniliprole in three field resistant populations were 2.41-, 2.54- and 2.60-times lower than that in the susceptible one. For the first time we experimentally proved that the G4946E mutation in PxRyR confers resistance to chlorantraniliprole in Plutella xylostella. These findings pave the way for the complete understanding of the mechanisms of diamide insecticides resistance in insects. © 2013 Society of Chemical Industry.

Structural basis of DNA target recognition by the B3 domain of Arabidopsis epigenome reader VAL1

PubMed Central

Sasnauskas, Giedrius; Kauneckaitė, Kotryna; Siksnys, Virginijus

2018-01-01

Abstract Arabidopsis thaliana requires a prolonged period of cold exposure during winter to initiate flowering in a process termed vernalization. Exposure to cold induces epigenetic silencing of the FLOWERING LOCUS C (FLC) gene by Polycomb group (PcG) proteins. A key role in this epigenetic switch is played by transcriptional repressors VAL1 and VAL2, which specifically recognize Sph/RY DNA sequences within FLC via B3 DNA binding domains, and mediate recruitment of PcG silencing machinery. To understand the structural mechanism of site-specific DNA recognition by VAL1, we have solved the crystal structure of VAL1 B3 domain (VAL1-B3) bound to a 12 bp oligoduplex containing the canonical Sph/RY DNA sequence 5′-CATGCA-3′/5′-TGCATG-3′. We find that VAL1-B3 makes H-bonds and van der Waals contacts to DNA bases of all six positions of the canonical Sph/RY element. In agreement with the structure, in vitro DNA binding studies show that VAL1-B3 does not tolerate substitutions at any position of the 5′-TGCATG-3′ sequence. The VAL1-B3–DNA structure presented here provides a structural model for understanding the specificity of plant B3 domains interacting with the Sph/RY and other DNA sequences. PMID:29660015

Semi-empirical seismic relations of A-F stars from COROT and Kepler legacy data

NASA Astrophysics Data System (ADS)

Moya, A.; Suárez, J. C.; García Hernández, A.; Mendoza, M. A.

2017-10-01

Asteroseismology is witnessing a revolution, thanks to high-precise asteroseismic space data (MOST, COROT, Kepler, BRITE) and their large ground-based follow-up programs. Those instruments have provided an unprecedented large amount of information, which allows us to scrutinize its statistical properties in the quest for hidden relations among pulsational and/or physical observables. This approach might be particularly useful for stars whose pulsation content is difficult to interpret. This is the case of intermediate-mass classical pulsating stars (I.e. γ Dor, δ Scuti, hybrids) for which current theories do not properly predict the observed oscillation spectra. Here, we establish a first step in finding such hidden relations from data mining techniques for these stars. We searched for those hidden relations in a sample of δ Scuti and hybrid stars observed by COROT and Kepler (74 and 153, respectively). No significant correlations between pairs of observables were found. However, two statistically significant correlations emerged from multivariable correlations in the observed seismic data, which describe the total number of observed frequencies and the largest one, respectively. Moreover, three different sets of stars were found to cluster according to their frequency density distribution. Such sets are in apparent agreement with the asteroseismic properties commonly accepted for A-F pulsating stars.

Total internal reflectance fluorescence imaging of genetically engineered ryanodine receptor-targeted Ca2+ probes in rat ventricular myocytes.

PubMed

Pahlavan, Sara; Morad, Marin

2017-09-01

The details of cardiac Ca 2+ signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca 2+ probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca 2+ nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, K d =150nM, or FKBP-GCaMP6, K d =240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP, 2 -targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images. FKBP-YCaMP signals were too small (∼20%) and too slow (2-3s) to detect Ca 2+ sparks, but the probe was effective in marking where Fluo-4 Ca 2+ sparks developed. FKBP-GCaMP6, on the other hand, produced rapidly decaying Ca 2+ signals that: a) had faster kinetics and activated synchronous with I Ca 3 but were of variable size at different z-lines and b) were accompanied by spatially confined spontaneous Ca 2+ sparks, originating from a subset of eager sites. The frequency of spontaneously occurring sparks was lower in FKBP-GCaMP6 infected myocytes as compared to Fluo-4 dialyzed myocytes, but isoproterenol enhanced their frequency more effectively than in Fluo-4 dialyzed cells. Nevertheless, isoproterenol failed to dissociate FKBP-GCaMP6 from the z-lines. The data suggests that FKBP-GCaMP6 binds predominantly to junctional RyR2s and has sufficient on-rate efficiency as to monitor the released Ca 2+ in individual dyadic clefts, and supports the idea that β-adrenergic agonists may modulate the stabilizing effects of native FKBP on RyR2. Copyright © 2017 Elsevier Ltd. All rights reserved.

HD 51844: An Am δ Scuti in a binary showing periastron brightening

NASA Astrophysics Data System (ADS)

Hareter, M.; Paparó, M.; Weiss, W.; García Hernández, A.; Borkovits, T.; Lampens, P.; Rainer, M.; De Cat, P.; Marcos-Arenal, P.; Vos, J.; Poretti, E.; Baglin, A.; Michel, E.; Baudin, F.; Catala, C.

2014-07-01

Context. Pulsating stars in binary systems are ideal laboratories to test stellar evolution and pulsation theory, since a direct, model-independent determination of component masses is possible. The high-precision CoRoT photometry allows a detailed view of the frequency content of pulsating stars, enabling detection of patterns in their distribution. The object HD 51844 is such a case showing periastron brightening instead of eclipses. Aims: We present a comprehensive study of the HD 51844 system, where we derive physical parameters of both components, the pulsation content and frequency patterns. Additionally, we obtain the orbital elements, including masses, and the chemical composition of the stars. Methods: Time series analysis using standard tools was employed to extract the pulsation frequencies. Photospheric abundances of 21 chemical elements were derived by means of spectrum synthesis. We derived orbital elements both by fitting the observed radial velocities and the light curves, and we did asteroseismic modelling as well. Results: We found that HD 51844 is a double lined spectroscopic binary. The determined abundances are consistent with δ Delphini classification. We determined the orbital period (33.498 ± 0.002 d), the eccentricity (0.484 ± 0.020), the mass ratio (0.988 ± 0.02), and the masses to 2.0 ± 0.2 M⊙ for both components. Only one component showed pulsation. Two p modes (f22 and f36) and one g mode (forb) may be tidally excited. Among the 115 frequencies, we detected triplets due to the frequency modulation, frequency differences connected to the orbital period, and unexpected resonances (3:2, 3:5, and 3:4), which is a new discovery for a δ Sct star. The observed frequency differences among the dominant modes suggest a large separation of 2.0-2.2 d-1, which are consistent with models of mean density of 0.063 g cm-3, and with the binary solution and TAMS evolutionary phase for the pulsating component. The binary evolution is in an intermediate evolutionary phase; the stellar rotation is super-synchronised, but circularisation of the orbit is not reached. Based on observations obtained with the HERMES spectrograph attached to the Mercator Telescope which is operated on the island of La Palma by the University of Leuven (IvS) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. The HERMES spectrograph is supported by the Fund for Scientific Research of Flanders (FWO), Belgium, the Research Council of K.U. Leuven, Belgium, the Fonds National de la Recherche Scientifique (FNRS), Belgium, the Royal Observatory of Belgium, the Observatoire de Genève, Switzerland and the Thüringer Landessternwarte Tautenburg, Germany. Based on CoRoT space-based photometric data; the CoRoT space mission was developed and operated by the French space agency CNES, with the participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain. Based on observations collected at La Silla Observatory, ESO (Chile) with the HARPS spectrograph at the 3.6 m telescope, under programme LP185.D-0056.Table 9 is available in electronic form at http://www.aanda.org

Long-Term Quadrature Light Variability in Early Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine J.; Wilson, R. E.; Vaccaro, T. R.

2014-01-01

Four years of Kepler observations have revealed a phenomenon in the light curves of short-period Algol-type eclipsing binaries that has never been reported from ground-based photometry. These systems display unequal brightness at their quadrature phases that numerically reverses over a time scale of about 100-400 days. We call these systems L/T (leading hemisphere/ trailing hemisphere) variables. Twenty-one such systems have so far been identified in the Kepler database and at least three classes of L/T behavior have been identified. The prototype is WX Draconis (A8V + K0IV, P=1.80 d) which shows L/ T light variations of 2-3%. The primary is a delta Scuti star with a dominant pulsation period of 41 m. The Kepler light curves are being analyzed with the 2013 version of the Wilson-Devinney (WD) program that includes major improvements in modeling star spots (i.e. spot motions due to drift and stellar rotation and spot growth and decay). Preliminary analysis of the WX Dra data suggests that the L/T variability can be fit with either an accretion hot spot on the primary (T = 2.3 T_phot) that jumps in longitude or a magnetic cool spotted region on the secondary. If the latter model is correct the dark region must occupy at least 20% of the surface of the facing hemisphere of the secondary if it is completely black, or a larger area if not completely black. In both hot and cool spot scenarios magnetic fields must play a role in the activity. Echelle spectra were recently secured with the KPNO 4-m telescope to determine the mass ratios of the L/T systems and their spectral types. This information will allow us to assess whether the hot or cool spot model explains the L/T activity. Progress toward this goal will be presented. Support from NASA grants NNX11AC78G and NNX12AE44G and USC’s Women in Science and Engineering (WiSE) program is greatly appreciated.

Proposal for mars express: detailed dds-test in the "inca city" and "csontváry" areas

NASA Astrophysics Data System (ADS)

Horvath, A.; Manrubia, S. C.; Ganti, T.; Berczi, S.; Gesztesi, A.; Fernandez-Remolar, D.; Prieto Ballesteros, O.; Szathmary, E.

2003-04-01

Analyis of Mars Global Surveyor MOC images taken in Martian winter and spring has revealed a peculiar spotting phenomenon on the dark dunes in the polar region of Mars [1]. These spots are named Dark Dune Spots (DDSs) and various hypotheses have been put forward for their origin and formation process, which fall into two main groups: geophysical and biological [2, 3, 4, 5 and 6]. Because the high-resolution images by MGS-MOC have shown well-developed and recurrent DDSs on some dark dune fields since the Southern winter of 1999 [5, 6 and 7], we have selected two areas of them. They are many dozen kilometers in size in the Southern polar region. Namely: the "Inca City" area (λ=295.3^oE, ϕ=81.5^oS) and the Northern part of Pityusa Patera (λ=37^oE, ϕ=66^oS), which we call "Csontváry" area. These two areas could be excellent test areas for Mars Express in order to reveal the mechanism of the formation, development and annual recurrence of the DDSs. For this we propose, that different instruments (HRSC, spectrometers, etc.) of the orbiter of the ESA Mars Express Mission should produce high-resolution images and spectral measurements of the frosted surface of the dark dunes of the "Inca City" and the Pityusa Patera from the second half of the Southern winter till the end of spring, with weekly regularity, because this may be sufficient to choose between the abiogenic and the biogenic origin of DDSs. Referenes [1] Malin, M. C. and Edgett, K. S.: 2000, Frosting and defrosting of Martian polar dunes, LPS XXXI, #1056, Houston-CD. [2] Horváth, A., Gánti, T., Gesztesi, A., Bérczi, Sz., Szathmáry, E., 2001, Probable evidences of recent biological activity on Mars: appearance and growing of dark dune spots in the south polar region. LPS XXXII, # 1543, Houston-CD. [3] Malin, M. C. and Edgett, K. S.: 2001, The Mars Global Surveyor Mars Orbiter Camera: Interplanetary Cruise through Primary Mission. J. Geophys. Res. 106 E10, p. 23,429-23,570. [4] Gánti, T., Horváth, A., Gesztesi, A., Bérczi, Sz., Szathmáry E.: 2002, Defrosting and Melting, not Defrosting Alone, Lunar Planetary Science XXXIII, #1221, Houston-CD. [5] Horváth, A., Bérczi, Sz., Gánti, T., Gesztesi, A., Szathmáry E.: 2002, The “Inca City” Region of Mars: Test field for Dark Dune Spots Origin, LPS XXXIII, #1109, Houston-CD. [6] Gánti, T., Horváth, A., Gesztesi, A., Bérczi, Sz., Szathmáry, E., 2003, Dark dune spots: possible biomarkers on Mars? OLEB in print. [7] Horváth, A., Gánti, T., Bérczi, Sz., Gesztesi, A., Szathmáry, E., 2003, Morphological analysis of annual recurrence of dark dune spots on Southern Polar Region, LPS XXXIV.

Projective limits of state spaces III. Toy-models

NASA Astrophysics Data System (ADS)

Lanéry, Suzanne; Thiemann, Thomas

2018-01-01

In this series of papers, we investigate the projective framework initiated by Kijowski (1977) and Okołów (2009, 2014, 2013) [1,2], which describes the states of a quantum theory as projective families of density matrices. A short reading guide to the series can be found in Lanéry (2016). A strategy to implement the dynamics in this formalism was presented in our first paper Lanéry and Thiemann (2017) (see also Lanéry, 2016, section 4), which we now test in two simple toy-models. The first one is a very basic linear model, meant as an illustration of the general procedure, and we will only discuss it at the classical level. In the second one, we reformulate the Schrödinger equation, treated as a classical field theory, within this projective framework, and proceed to its (non-relativistic) second quantization. We are then able to reproduce the physical content of the usual Fock quantization.

Thymoma in myasthenia gravis: from diagnosis to treatment.

PubMed

Romi, Fredrik

2011-01-01

One half of cortical thymoma patients develop myasthenia gravis (MG), while 15% of MG patients have thymomas. MG is a neuromuscular junction disease caused in 85% of the cases by acetylcholine receptor (AChR) antibodies. Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG and 50% of late-onset MG (MG onset ≥50 years), are associated with severe disease, and may predict thymoma MG outcome. Nonlimb symptom profile at MG onset with bulbar, ocular, neck, and respiratory symptoms should raise the suspicion about the presence of thymoma in MG. The presence of titin and RyR antibodies in an MG patient younger than 60 years strongly suggests a thymoma, while their absence at any age strongly excludes thymoma. Thymoma should be removed surgically. Prethymectomy plasmapheresis/iv-IgG should be considered before thymectomy. The pharmacological treatment does not differ from nonthymoma MG, except for tacrolimus which is an option in difficult thymoma and nonthymoma MG cases with RyR antibodies.

[Thymectomy and muscle antibodies in myasthenia gravis].

PubMed

Romi, Fredrik; Gilhus, Nils Erik; Aarli, Johan A

2004-03-04

Thymectomy as a treatment for myasthenia gravis (MG) is widely carried out as there is good clinical evidence for post-thymectomy improvement in younger MG patients. We examined the relationship between thymectomy, MG severity, the occurrence of muscle autoantibodies against acetylcholine receptor (AChR), titin, and ryanodine receptor (RyR), and pharmacological treatment in 52 early and 43 late-onset MG patients. Thymectomy in early-onset MG gave a rapid, highly significant, and long-lasting improvement during the first one to two years after surgery. Several patients had a remission. In late-onset MG, thymectomy did not provide the same improvement, but these patients responded well to immunosuppressive drug treatment, which was necessary in 75% of late-onset MG patients compared to only 25% of early-onset patients. The concentration of AChR, titin, and RyR antibodies did not predict the outcome of thymectomy. The occurrence of titin/RyR antibodies in late-onset MG indicated a less favorable prognosis.

Cloning of apg-2 encoding a novel member of heat shock protein 110 family.

PubMed

Kaneko, Y; Kimura, T; Kishishita, M; Noda, Y; Fujita, J

1997-04-11

Chinese hamster heat shock protein 110-encoding gene (hsp110), mouse apg-1 and human hsp70RY are structurally related genes, with the first two encoding about 110-kDa HSPs [Yoon et al. (1995) J. Biol. Chem. 270, 15725-15733; Kaneko et al. (1997) J. Biol. Chem., in press; Fathallah et al. (1993) J. Immunol. 151, 810-813]. Using apg-1 cDNA as a probe, we isolated a novel cDNA, apg-2 from a mouse testis cDNA library, which was highly homologous to human hsp70RY. However, the predicted amino acid (aa) sequence of APG-2 was longer (841 aa) than that of HSP70RY (701 aa) and comparable to those of HSP110 and APG-1. Northern blot analysis revealed that the expression of apg-2 transcripts was ubiquitous in various mouse tissues, and most abundant in the testis and ovary. While induction of hsp70 transcripts was observed in mouse TAMA26 Sertoli cells and NIH/3T3 fibroblasts on temperature shift from 37 degrees C to 42 degrees C (traditional heat shock) or from 32 degrees C to 39 degrees C, apg-2 transcripts were not induced under either condition. These results suggest that apg-2 is an isoform of mouse homolog of hsp70RY, but that it belongs to the hsp110 family instead of hsp70 family, and that it plays a role under non-stress conditions.

Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

PubMed Central

Vesely, C; Frech, C; Eckert, C; Cario, G; Mecklenbräuker, A; zur Stadt, U; Nebral, K; Kraler, F; Fischer, S; Attarbaschi, A; Schuster, M; Bock, C; Cavé, H; von Stackelberg, A; Schrappe, M; Horstmann, M A; Mann, G; Haas, O A; Panzer-Grümayer, R

2017-01-01

Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1’s critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias. PMID:27899802

RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism

PubMed Central

Wang, Yue Yi; Mesirca, Pietro; Marqués-Sulé, Elena; Villejoubert, Olivier; D’Ocon, Pilar; Ruiz, Cristina; Domingo, Diana; Zorio, Esther; Mangoni, Matteo E.; Benitah, Jean-Pierre; Gómez, Ana María

2017-01-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the “funny” current (If ). The L-type Ca2+ current was reduced in KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to disrupted crosstalk between the “voltage” and “Ca2+” clock, and the mechanisms of pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This finding was consistent with a higher Ca2+ leak during diastolic periods produced by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling between Ca2+ and voltage clocks. PMID:28422759

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle.

PubMed

Tazzeo, T; Zhang, Y; Keshavjee, S; Janssen, L J

2008-08-01

Several putative roles for ryanodine receptors (RyR) were investigated in human and bovine airway smooth muscle. Changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane current were investigated in single cells by confocal fluorimetry and patch-clamp electrophysiology, respectively, whereas mechanical activity was monitored in intact strips with force transducers. RyR released Ca2+ from the sarcoplasmic reticulum in a ryanodine- and chloroethyl phenol (CEP)-sensitive fashion. Neither ryanodine nor CEP inhibited responses to KCl, cholinergic agonists or serotonin, indicating no direct role for RyR in contraction; in fact, there was some augmentation of these responses. In tissues pre-contracted with carbachol, the concentration-response relationships for isoproterenol and salmeterol were unaffected by ryanodine; relaxations due to a nitric oxide donor were also largely unaffected. Finally, it was examined whether RyR were involved in regulating [Ca2+]i within the subplasmalemmal space using patch-clamp electrophysiology as well as Ca2+ fluorimetry: isoproterenol increased [Ca2+]i- and Ca2+-dependent K+ current activity in a ryanodine-sensitive fashion. In conclusion, ryanodine receptors in airway smooth muscle are not important in directly mediating contraction or relaxation. The current authors speculate instead that these allow the sarcoplasmic reticulum to release Ca2+ towards the plasmalemma (to unload an overly full Ca2+ store and/or increase the Ca2+-buffering capacity of the sarcoplasmic reticulum) without affecting bronchomotor tone.

Maternal high-altitude hypoxia and suppression of ryanodine receptor-mediated Ca2+ sparks in fetal sheep pulmonary arterial myocytes

PubMed Central

Hadley, Scott R.; Blood, Quintin; Rubalcava, Monica; Waskel, Edith; Lumbard, Britney; Le, Petersen; Longo, Lawrence D.; Buchholz, John N.

2012-01-01

Ca2+ sparks are fundamental Ca2+ signaling events arising from ryanodine receptor (RyR) activation, events that relate to contractile and dilatory events in the pulmonary vasculature. Recent studies demonstrate that long-term hypoxia (LTH) can affect pulmonary arterial reactivity in fetal, newborn, and adult animals. Because RyRs are important to pulmonary vascular reactivity and reactivity changes with ontogeny and LTH we tested the hypothesis that RyR-generated Ca2+ signals are more active before birth and that LTH suppresses these responses. We examined these hypotheses by performing confocal imaging of myocytes in living arteries and by performing wire myography studies. Pulmonary arteries (PA) were isolated from fetal, newborn, or adult sheep that lived at low altitude or from those that were acclimatized to 3,801 m for > 100 days. Confocal imaging demonstrated preservation of the distance between the sarcoplasmic reticulum, nucleus, and plasma membrane in PA myocytes. Maturation increased global Ca2+ waves and Ca2+ spark activity, with sparks becoming larger, wider, and slower. LTH preferentially depressed Ca2+ spark activity in immature pulmonary arterial myocytes, and these sparks were smaller, wider, and slower. LTH also suppressed caffeine-elicited contraction in fetal PA but augmented contraction in the newborn and adult. The influence of both ontogeny and LTH on RyR-dependent cell excitability shed new light on the therapeutic potential of these channels for the treatment of pulmonary vascular disease in newborns as well as adults. PMID:22962012

Integrins protect cardiomyocytes from ischemia/reperfusion injury

PubMed Central

Okada, Hideshi; Lai, N. Chin; Kawaraguchi, Yoshitaka; Liao, Peter; Copps, Jeffrey; Sugano, Yasuo; Okada-Maeda, Sunaho; Banerjee, Indroneal; Schilling, Jan M.; Gingras, Alexandre R.; Asfaw, Elizabeth K.; Suarez, Jorge; Kang, Seok-Min; Perkins, Guy A.; Au, Carol G.; Israeli-Rosenberg, Sharon; Manso, Ana Maria; Liu, Zheng; Milner, Derek J.; Kaufman, Stephen J.; Patel, Hemal H.; Roth, David M.; Hammond, H. Kirk; Taylor, Susan S.; Dillmann, Wolfgang H.; Goldhaber, Joshua I.; Ross, Robert S.

2013-01-01

Ischemic damage is recognized to cause cardiomyocyte (CM) death and myocardial dysfunction, but the role of cell-matrix interactions and integrins in this process has not been extensively studied. Expression of α7β1D integrin, the dominant integrin in normal adult CMs, increases during ischemia/reperfusion (I/R), while deficiency of β1 integrins increases ischemic damage. We hypothesized that the forced overexpression of integrins on the CM would offer protection from I/R injury. Tg mice with CM-specific overexpression of integrin α7β1D exposed to I/R had a substantial reduction in infarct size compared with that of α5β1D-overexpressing mice and WT littermate controls. Using isolated CMs, we found that α7β1D preserved mitochondrial membrane potential during hypoxia/reoxygenation (H/R) injury via inhibition of mitochondrial Ca2+ overload but did not alter H/R effects on oxidative stress. Therefore, we assessed Ca2+ handling proteins in the CM and found that β1D integrin colocalized with ryanodine receptor 2 (RyR2) in CM T-tubules, complexed with RyR2 in human and rat heart, and specifically bound to RyR2 amino acids 165–175. Integrins stabilized the RyR2 interdomain interaction, and this stabilization required integrin receptor binding to its ECM ligand. These data suggest that α7β1D integrin modifies Ca2+ regulatory pathways and offers a means to protect the myocardium from ischemic injury. PMID:24091324

GREEN TEA CATECHINS ARE POTENT SENSITIZERS OF RYANODINE RECEPTOR TYPE 1 (RYR1)

PubMed Central

Feng, Wei; Cherednichenko, Gennady; Ward, Chris W.; Padilla, Isela T.; Cabrales, Elaine; Lopez, José R.; Eltit, José M.; Allen, Paul D.; Pessah, Isaac N.

2010-01-01

Catechins, polyphenols extracted from green tea leaves, have a broad range of biological activities although the specific molecular mechanisms responsible are not known. At the high experimental concentrations typically used polyphenols bind to membrane phospholipid and also are easily auto-oxidized to generate superoxide anion and semiquinones, and can adduct to protein thiols. We report that the type 1 ryanodine receptor (RyR1) is a molecular target that responds to nanomolar (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin-3-gallate (ECG). Single channel analyses demonstrate EGCG (5-10nM) increases channel open probability (Po) 2-fold, by lengthening open dwell time. The degree of channel activation is concentration dependent and is rapidly and fully reversible. Four related catechins, EGCG, ECG, EGC ((−)-epigallocatechin) and EC ((−)-epicatechin) showed a rank order of activity toward RyR1 (EGCG>ECG>>EGC>>>EC). EGCG and ECG enhance the sensitivity of RyR1 to activation by ≤100μM cytoplasmic Ca2+ without altering inhibitory potency by >100μM Ca2+. EGCG as high as 10μM in the extracellular medium potentiated Ca2+ transient amplitudes evoked by electrical stimuli applied to intact myotubes and adult FDB fibers, without eliciting spontaneous Ca2+ release or slowing Ca2+ transient recovery. The results identify RyR1 as a sensitive target for the major tea catechins EGCG and ECG, and this interaction is likely to contribute to their observed biological activities. PMID:20471964

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.

Identification and period investigation of pulsation variable star UY Camelopardalis, an RR Lyrae star in binary system

NASA Astrophysics Data System (ADS)

Li, Lin-Jia; Qian, Sheng-Bang; Voloshina, Irina; Metlov, Vladimir G.; Zhu, Li-Ying; Liao, Wen-Ping

2018-06-01

We present photometric measurements of the short period variable star UY Cam, which has been classified as a δ Scuti or c-type RR Lyrae (RRc) variable in different catalogs. Based on the analyses on Fourier coefficients and (NUV - V)0, we find that UY Cam is probably an RRc star. We obtain 58 new times of light maximum for UY Cam based on several sky surveys and our observations. Combining these with the times of light maximum in literature, a total of 154 times of light maximum are used to analyze the O - C diagram of UY Cam. The results show that the O - C pattern can be described by a downward parabolic component with a rate of -6.86 ± 0.47 × 10-11 d d-1, and a cyclic variation with a period of 65.7 ± 2.4 yr. We suppose these components are caused by the stellar evolution and the light travel time effect (LiTE) of a companion in elliptical orbit, respectively. By calculation, the minimum mass of the potential companion is about 0.17 M⊙, and its mass should be less than or equal to the pulsation primary star when the inclination i > 22.5°D. Therefore, the companion should be a low-mass star, like a late-type main-sequence star or a white dwarf. Due to the unique property of UY Cam, we suggest that more observations and studies on UY Cam and other RRc stars are needed to check the nature of these stars, including the pulsations and binarities.

A Strategic Approach to the Maritime-Continental Strategy Debate

DTIC Science & Technology

1987-02-01

TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE A Strategic Approach to the Maritime-Continental Strategy Debate 5a. CONTRACT NUMBER 5b...War Col ]. e C.le, Fort Les ].ey J. McNair, Washington, DC 70319-6000. ii THE NATIONAL. WAR COLLEL:iE S’I’RATEGI C S’FUDIES REF:’OR’I" ABSTRACf...cesses, and ’the study ,’-,f strategi,- the,:,ry alqd histc, ry. Itl additi,:,n to his civilian gc, verr ~r,~ent expc.ri .... ence, his rrlilitary

An annotated checklist of the chrysidid wasps (Hymenoptera, Chrysididae) from China

PubMed Central

Rosa, Paolo; Wei, Na-sen; Xu, Zai-fu

2014-01-01

Abstract An annotated checklist of the Chinese Chrysididae is provided. The list includes 188 species and subspecies in twenty three genera of five subfamilies. Four species are proposed as new combinations: Hedychridium cupreum asianum (Linsenmaier, 1997), Philoctetes deauratus (Mocsáry, 1914), Philoctetes mordvilkoi (Semenov-Tian-Shanskij, 1932), and Pseudomalus hypocritus (du Buysson, 1893). Two species are revalidated: Chrysis consobrina Mocsáry, 1889, and Philoctetes mongolicus (du Buysson, 1901). Historical data with comments on the current taxonomic position, and the pictures of sixty five types are also given. PMID:25493069

Military Review. January-February 2010

DTIC Science & Technology

2010-01-01

MILITARY REVIEW 64 C op yr ig ht U nk no w n, C ou rte sy o f H ar ry S . T ru m an L ib ra ry Farewell reception and luncheon in honor of General...Whether it is perfume or a new food item, if the sample is pleasing, the customer may purchase the product. As another example, movie MILITARY...REVIEW  January-February 2010 115 previews online, in a theater, or on a DVD often entice people to watch the movie in a theater or rent or purchase

The Simulation Operations Officer in a Sustainment Brigade

DTIC Science & Technology

2016-05-17

want to assist FA57s who will be assigned to sustain- ment brigades in the future and to describe the training exercises and road to war (RTW) that... constructive simulations and knowledge manage- ment (KM). A primary difficulty units may face is how to effectively train a “hyper- modular” formation...integrated into the brigade RTW. Th e FA57 can plan a MCSIT to train the brigade. (See CO M M EN TA RY CO M M EN TA RY 3rd Sustainment Brigade Road to

Nitric Oxide Synthase 1 Modulates Basal and β-Adrenergic-Stimulated Contractility by Rapid and Reversible Redox-Dependent S-Nitrosylation of the Heart

PubMed Central

Vielma, Alejandra Z.; León, Luisa; Fernández, Ignacio C.; González, Daniel R.

2016-01-01

S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC. Selective NOS-1 blockade with S-methyl-L-thiocitrulline (SMTC) and Nω-propyl-l-arginine decreased basal contractility and relaxation (−25–30%) and basal S-nitrosylation of total proteins (−25–60%), RyR2, SERCA2 and LTCC (−60–75%). NOS-1 inhibition reduced (−25–40%) the inotropic response and protein S-nitrosylation induced by isoproterenol, particularly that of RyR2 (−85±7%). Tempol, a superoxide scavenger, mimicked the effects of NOS-1 inhibition on inotropism and protein S-nitrosylation; whereas selective NOS-3 inhibitor L-N5-(1-Iminoethyl)ornithine had no effect. Inhibition of NOS-1 did not affect phospholamban phosphorylation, but reduced its oligomerization. Attenuation of contractility was abolished by PKA blockade and unaffected by guanylate cyclase inhibition. Additionally, in isolated mouse cardiomyocytes, NOS-1 inhibition or removal reduced the Ca2+-transient amplitude and sarcomere shortening induced by isoproterenol or by direct PKA activation. We conclude that 1) normal cardiac performance requires basal NOS-1 activity and S-nitrosylation of the calcium-cycling machinery; 2) β-adrenergic stimulation induces rapid and reversible NOS-1 dependent, PKA and ROS-dependent, S-nitrosylation of RyR2 and other proteins, accounting for about one third of its inotropic effect. PMID:27529477

Allele-Specific Silencing of Mutant mRNA Rescues Ultrastructural and Arrhythmic Phenotype in Mice Carriers of the R4496C Mutation in the Ryanodine Receptor Gene (RYR2).

PubMed

Bongianino, Rossana; Denegri, Marco; Mazzanti, Andrea; Lodola, Francesco; Vollero, Alessandra; Boncompagni, Simona; Fasciano, Silvia; Rizzo, Giulia; Mangione, Damiano; Barbaro, Serena; Di Fonso, Alessia; Napolitano, Carlo; Auricchio, Alberto; Protasi, Feliciano; Priori, Silvia G

2017-08-18

Mutations in the cardiac Ryanodine Receptor gene ( RYR2 ) cause dominant catecholaminergic polymorphic ventricular tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals exposed to emotions or physical exercise. We investigated the efficacy of allele-specific silencing by RNA interference to prevent CPVT phenotypic manifestations in our dominant CPVT mice model carriers of the heterozygous mutation R4496C in RYR2 . We developed an in vitro mRNA and protein-based assays to screen multiple siRNAs for their ability to selectively silence mutant RYR2 -R4496C mRNA over the corresponding wild-type allele. For the most performant of these siRNAs (siRYR2-U10), we evaluated the efficacy of an adeno-associated serotype 9 viral vector (AAV9) expressing miRYR2-U10 in correcting RyR2 (Ryanodine Receptor type 2 protein) function after in vivo delivery by intraperitoneal injection in neonatal and adult RyR2 R4496C/+ (mice heterozygous for the R4496C mutation in the RyR2) heterozygous CPVT mice. Transcriptional analysis showed that after treatment with miRYR2-U10, the ratio between wild-type and mutant RYR2 mRNA was doubled (from 1:1 to 2:1) confirming the ability of miRYR2-U10 to selectively inhibit RYR2 -R4496C mRNA, whereas protein quantification showed that total RyR2 was reduced by 15% in the heart of treated mice. Furthermore, AAV9-miRYR2-U10 effectively (1) reduced isoproterenol-induced delayed afterdepolarizations and triggered activity in infected cells, (2) reduced adrenergically mediated ventricular tachycardia in treated mice, (3) reverted ultrastructural abnormalities of junctional sarcoplasmic reticulum and transverse tubules, and (4) attenuated mitochondrial abnormalities. The study demonstrates that allele-specific silencing with miRYR2-U10 prevents life-threatening arrhythmias in CPVT mice, suggesting that the reduction of mutant RyR2 may be a novel therapeutic approach for CPVT. © 2017 American Heart Association, Inc.

Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure.

PubMed

Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

2010-05-26

Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca(2+) pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca(2+) leak in the form of Ca(2+) quarks, increase the probability of occurrence of spontaneous Ca(2+) waves even with smaller SR Ca(2+) stores, accelerate Ca(2+) wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca(2+) wave model under HF conditions provides a new view of Ca(2+) dynamics that could not be mimicked by adjusting traditional parameters involved in Ca(2+) release units and other ion channels, and contributes to understanding the underlying mechanism of HF.

MeRy-B: a web knowledgebase for the storage, visualization, analysis and annotation of plant NMR metabolomic profiles

PubMed Central

2011-01-01

Background Improvements in the techniques for metabolomics analyses and growing interest in metabolomic approaches are resulting in the generation of increasing numbers of metabolomic profiles. Platforms are required for profile management, as a function of experimental design, and for metabolite identification, to facilitate the mining of the corresponding data. Various databases have been created, including organism-specific knowledgebases and analytical technique-specific spectral databases. However, there is currently no platform meeting the requirements for both profile management and metabolite identification for nuclear magnetic resonance (NMR) experiments. Description MeRy-B, the first platform for plant 1H-NMR metabolomic profiles, is designed (i) to provide a knowledgebase of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata, (ii) for queries and visualization of the data, (iii) to discriminate between profiles with spectrum visualization tools and statistical analysis, (iv) to facilitate compound identification. It contains lists of plant metabolites and unknown compounds, with information about experimental conditions, the factors studied and metabolite concentrations for several plant species, compiled from more than one thousand annotated NMR profiles for various organs or tissues. Conclusion MeRy-B manages all the data generated by NMR-based plant metabolomics experiments, from description of the biological source to identification of the metabolites and determinations of their concentrations. It is the first database allowing the display and overlay of NMR metabolomic profiles selected through queries on data or metadata. MeRy-B is available from http://www.cbib.u-bordeaux2.fr/MERYB/index.php. PMID:21668943

Chlorantraniliprole resistance and its biochemical and new molecular target mechanisms in laboratory and field strains of Chilo suppressalis (Walker).

PubMed

Sun, Yang; Xu, Lu; Chen, Qiong; Qin, Wenjing; Huang, Shuijin; Jiang, Ying; Qin, Houguo

2018-06-01

The rice striped stem borer (SSB), Chilo suppressalis (Walker), is one of the most economically important and destructive rice pests in China. To date, the efficiency of conventional insecticides has decreased greatly because of the development of high resistance. Since the introduction of chlorantraniliprole in 2008, SSB has presented resistance issues. In this study, laboratory resistant strains R1 and R2 [resistance ratio (RR) of 38.8 and 110.4, respectively] were established and a field population HR (RR of 249.6) was collected. Synergist assessment and enzyme activity data suggested the potential involvement of P450s and esterases in the resistance mechanism. No target (ryanodine receptor, RyR) mutation was found in R1, but a novel mutation Y4667D was found in R2. At the same position of RyR in HR strain, Y4667D and Y4667C were observed at low frequencies. In addition, the conserved mutation I4758M was found with a frequency of 94.4%. RyR mRNA expression was significantly lower in R1, R2 and HR than in S. When treated with chlorantraniliprole, RyR mRNA expression in all four strains was downregulated to ∼ 50%. A comprehensive analysis, including biochemical, target mutations and target mRNA expression, was conducted in an attempt to interpret the chlorantraniliprole resistance mechanism in both laboratory and field SSB strains. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Transactivation of the Brassica napus napin promoter by ABI3 requires interaction of the conserved B2 and B3 domains of ABI3 with different cis-elements: B2 mediates activation through an ABRE, whereas B3 interacts with an RY/G-box.

PubMed

Ezcurra, I; Wycliffe, P; Nehlin, L; Ellerström, M; Rask, L

2000-10-01

The transcriptional activator ABI3 is a key regulator of gene expression during embryo maturation in crucifers. In monocots, the related VP1 protein regulates the Em promoter synergistically with abscisic acid (ABA). We identified cis-elements in the Brassica napus napin napA promoter mediating regulation by ABI3 and ABA, by analyzing substitution mutation constructs of napA in transgenic tobacco plantlets ectopically expressing ABI3. In transient analysis using particle bombardment of tobacco leaf sections, a tetramer of the distB ABRE (abscisic acid-responsive element) mediated transactivation by ABI3 and ABI3-dependent response to ABA, whereas a tetramer of the composite RY/G complex, containing RY repeats and a G-box, mediated only ABA-independent transactivation by ABI3. Deletion of the conserved B2 and B3 domains of ABI3 abolished transactivation of napA by ABI3. The two domains of ABI3 interact with different cis-elements: B2 is necessary for ABA-independent and ABA-dependent activations through the distB ABRE, whereas B3 interacts with the RY/G complex. Thus B2 mediates the interaction of ABI3 with the protein complex at the ABRE. The regulation of napA by ABI3 differs from Em regulation by VP1, in that the B3 domain of ABI3 is essential for the ABA-dependent regulation of napA.

Analysis and explanation of the Thiéry-Wundt illusion.

PubMed

Day, Ross H; Kimm, Andrew C

2010-01-01

The midpoint of the axis of bisection in a triangle appears to be displaced toward the apex so that the apical extent seems to be shorter than the basal extent, an effect originally reported in 1895 by Thiéry and later in 1898 by Wundt and, therefore, referred to here as the Thiéry-Wundt illusion. Following a demonstration strongly suggesting that the illusion is yet another version of the Müller-Lyer effect in a stimulus figure with inward-directed angles, four exploratory experiments designed to throw more light on this group of illusions are reported. The first showed that the effect occurs in an open angle, between converging lines that do not meet to form an apex, between converging stepped lines, and when one of the converging lines is removed, leaving a single oblique line. The other three experiments showed that the illusion also occurs in an open semicircle and a rectangular bracket, is weakened by the addition of a complete or partial baseline to form a triangle, and weakly but reliably when the angle is minimally formed from dots marking the ends of oblique lines. On the basis of these data, Judd's version of the conventional Müller-Lyer figure, and informal but easily repeatable observations, it is concluded that the Thiéry-Wundt illusion is, like other variants of the Müller-Lyer group of illusions, due to a process of directional biasing-an extension of the concept of biasing proposed originally by Morgan et al (1990, Vision Research 30 1793 1810).

Activity-induced Ca2+ signaling in perisynaptic Schwann cells of the early postnatal mouse is mediated by P2Y1 receptors and regulates muscle fatigue

PubMed Central

Heredia, Dante J; Feng, Cheng-Yuan; Hennig, Grant W; Renden, Robert B

2018-01-01

Perisynaptic glial cells respond to neural activity by increasing cytosolic calcium, but the significance of this pathway is unclear. Terminal/perisynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction that respond to nerve-derived substances such as acetylcholine and purines. Here, we provide genetic evidence that activity-induced calcium accumulation in neonatal TPSCs is mediated exclusively by one subtype of metabotropic purinergic receptor. In P2ry1 mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue in P2ry1 mutants was more greatly exacerbated by exposure to high potassium than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reduced P2ry1 mutants. These results suggest that activity-induced calcium responses in TPSCs regulate postsynaptic function and muscle fatigue by regulating perisynaptic potassium. PMID:29384476

The molecular basis of the genesis of basal tone in internal anal sphincter

PubMed Central

Zhang, Cheng-Hai; Wang, Pei; Liu, Dong-Hai; Chen, Cai-Ping; Zhao, Wei; Chen, Xin; Chen, Chen; He, Wei-Qi; Qiao, Yan-Ning; Tao, Tao; Sun, Jie; Peng, Ya-Jing; Lu, Ping; Zheng, Kaizhi; Craige, Siobhan M.; Lifshitz, Lawrence M.; Keaney Jr, John F.; Fogarty, Kevin E.; ZhuGe, Ronghua; Zhu, Min-Sheng

2016-01-01

Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca2+ channels (VDCCs) or TMEM16A Ca2+-activated Cl− channels significantly changes global cytosolic Ca2+ concentration ([Ca2+]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca2+]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca2+]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence. PMID:27101932

21st Century SOF: Toward an American Theory of Special Operations

DTIC Science & Technology

2013-04-01

century order. However, non-state actors can also pursue destructive ends that contribute to disorder and instability. It is worth noting that other...JS O U R ep o rt 13 -1 21st C en tu ry S O F: To w a rd a n A m erica n Th eo ry o f S p ecia l O p eratio n s Ya rger 21st Century ...21st Century SOF: Toward an American Theory of Special Operations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Air Traffic Control/Active Beacon Collision Avoidance System Knoxville Simulation.

DTIC Science & Technology

1980-05-01

I’s & AIRCRAFT 2’s POSITION VECTOR. ENTER (X1l,Y,Zl,,ZI,2) & (X2,Y2,Z2,X2,Y2,i2) As x = XI-X2 Y= Yl-Y2 VRX =Xi-X2 VRY = YI-Y2 MD2 -(4X*\\’RY - AY*vHJ...2 VRX 2 + vRy 2 M SQRT(MD2) YES MD> MDCM FILTER + OR - COMAND IF FITER VAVE TITRj-SITnLD PERFORMANCE LEATl. VALIE 3 o . U mi 5 3.0 1in t ;u~i:F-2

First Student Project at the University of Tennessee at Martin Observatory

NASA Astrophysics Data System (ADS)

Crews, Lionel J.; Turner, K.; Wesner, P.

2011-05-01

The University of Tennessee at Martin has recently completed the construction and setup of an observatory. The dome houses a 16" Meade telescope with SBIG STL-11000M CCD. For its first project, observations of the Delta Scuti type variable SZ Lynx were taken in March and analyzed using MiraPRO. A simple ephemeris calculation was done, and compared to previous results. This project was done under the University Scholars program, a four year scholarship program which includes a faculty-mentored research project.

First scattered light detection of a nearly edge-on transition disk around the T Tauri star RY Lupi

NASA Astrophysics Data System (ADS)

Langlois, M.; Pohl, A.; Lagrange, A.-M.; Maire, A.-L.; Mesa, D.; Boccaletti, A.; Gratton, R.; Denneulin, L.; Klahr, H.; Vigan, A.; Benisty, M.; Dominik, C.; Bonnefoy, M.; Menard, F.; Avenhaus, H.; Cheetham, A.; Van Boekel, R.; de Boer, J.; Chauvin, G.; Desidera, S.; Feldt, M.; Galicher, R.; Ginski, C.; Girard, J. H.; Henning, T.; Janson, M.; Kopytova, T.; Kral, Q.; Ligi, R.; Messina, S.; Peretti, S.; Pinte, C.; Sissa, E.; Stolker, T.; Zurlo, A.; Magnard, Y.; Blanchard, P.; Buey, T.; Suarez, M.; Cascone, E.; Moller-Nilsson, O.; Weber, L.; Petit, C.; Pragt, J.

2018-06-01

Context. Transition disks are considered sites of ongoing planet formation, and their dust and gas distributions could be signposts of embedded planets. The transition disk around the T Tauri star RY Lup has an inner dust cavity and displays a strong silicate emission feature. Aims: Using high-resolution imaging we study the disk geometry, including non-axisymmetric features, and its surface dust grain, to gain a better understanding of the disk evolutionary process. Moreover, we search for companion candidates, possibly connected to the disk. Methods: We obtained high-contrast and high angular resolution data in the near-infrared with the VLT/SPHERE extreme adaptive optics instrument whose goal is to study the planet formation by detecting and characterizing these planets and their formation environments through direct imaging. We performed polarimetric imaging of the RY Lup disk with IRDIS (at 1.6 μm), and obtained intensity images with the IRDIS dual-band imaging camera simultaneously with the IFS spectro-imager (0.9-1.3 μm). Results: We resolved for the first time the scattered light from the nearly edge-on circumstellar disk around RY Lup, at projected separations in the 100 au range. The shape of the disk and its sharp features are clearly detectable at wavelengths ranging from 0.9 to 1.6 μm. We show that the observed morphology can be interpreted as spiral arms in the disk. This interpretation is supported by in-depth numerical simulations. We also demonstrate that these features can be produced by one planet interacting with the disk. We also detect several point sources which are classified as probable background objects.

Insulin elicits a ROS-activated and an IP₃-dependent Ca²⁺ release, which both impinge on GLUT4 translocation.

PubMed

Contreras-Ferrat, Ariel; Llanos, Paola; Vásquez, César; Espinosa, Alejandra; Osorio-Fuentealba, César; Arias-Calderon, Manuel; Lavandero, Sergio; Klip, Amira; Hidalgo, Cecilia; Jaimovich, Enrique

2014-05-01

Insulin signaling includes generation of low levels of H2O2; however, its origin and contribution to insulin-stimulated glucose transport are unknown. We tested the impact of H2O2 on insulin-dependent glucose transport and GLUT4 translocation in skeletal muscle cells. H2O2 increased the translocation of GLUT4 with an exofacial Myc-epitope tag between the first and second transmembrane domains (GLUT4myc), an effect additive to that of insulin. The anti-oxidants N-acetyl L-cysteine and Trolox, the p47(phox)-NOX2 NADPH oxidase inhibitory peptide gp91-ds-tat or p47(phox) knockdown each reduced insulin-dependent GLUT4myc translocation. Importantly, gp91-ds-tat suppressed insulin-dependent H2O2 production. A ryanodine receptor (RyR) channel agonist stimulated GLUT4myc translocation and insulin stimulated RyR1-mediated Ca(2+) release by promoting RyR1 S-glutathionylation. This pathway acts in parallel to insulin-mediated stimulation of inositol-1,4,5-trisphosphate (IP3)-activated Ca(2+) channels, in response to activation of phosphatidylinositol 3-kinase and its downstream target phospholipase C, resulting in Ca(2+) transfer to the mitochondria. An inhibitor of IP3 receptors, Xestospongin B, reduced both insulin-dependent IP3 production and GLUT4myc translocation. We propose that, in addition to the canonical α,β phosphatidylinositol 3-kinase to Akt pathway, insulin engages both RyR-mediated Ca(2+) release and IP3-receptor-mediated mitochondrial Ca(2+) uptake, and that these signals jointly stimulate glucose uptake.

De novo RNA-Seq based transcriptome analysis of Papiliotrema laurentii strain RY1 under nitrogen starvation.

PubMed

Sarkar, Soumyadev; Chakravorty, Somnath; Mukherjee, Avishek; Bhattacharya, Debanjana; Bhattacharya, Semantee; Gachhui, Ratan

2018-03-01

Nitrogen is a key nutrient for all cell forms. Most organisms respond to nitrogen scarcity by slowing down their growth rate. On the contrary, our previous studies have shown that Papiliotrema laurentii strain RY1 has a robust growth under nitrogen starvation. To understand the global regulation that leads to such an extraordinary response, we undertook a de novo approach for transcriptome analysis of the yeast. Close to 33 million sequence reads of high quality for nitrogen limited and enriched condition were generated using Illumina NextSeq500. Trinity analysis and clustered transcripts annotation of the reads produced 17,611 unigenes, out of which 14,157 could be annotated. Gene Ontology term analysis generated 44.92% cellular component terms, 39.81% molecular function terms and 15.24% biological process terms. The most over represented pathways in general were translation, carbohydrate metabolism, amino acid metabolism, general metabolism, folding, sorting, degradation followed by transport and catabolism, nucleotide metabolism, replication and repair, transcription and lipid metabolism. A total of 4256 Single Sequence Repeats were identified. Differential gene expression analysis detected 996 P-significant transcripts to reveal transmembrane transport, lipid homeostasis, fatty acid catabolism and translation as the enriched terms which could be essential for Papiliotrema laurentii strain RY1 to adapt during nitrogen deprivation. Transcriptome data was validated by quantitative real-time PCR analysis of twelve transcripts. To the best of our knowledge, this is the first report of Papiliotrema laurentii strain RY1 transcriptome which would play a pivotal role in understanding the biochemistry of the yeast under acute nitrogen stress and this study would be encouraging to initiate extensive investigations into this Papiliotrema system. Copyright © 2017 Elsevier B.V. All rights reserved.

Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial.

PubMed

Ensor, Hannah M; Schwab, Claire; Russell, Lisa J; Richards, Sue M; Morrison, Heather; Masic, Dino; Jones, Lisa; Kinsey, Sally E; Vora, Ajay J; Mitchell, Christopher D; Harrison, Christine J; Moorman, Anthony V

2011-02-17

Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.

T-tubule Disruption Promotes Calcium Alternans in Failing Ventricular Myocytes: Mechanistic Insights from Computational Modeling

PubMed Central

Nivala, Michael; Song, Zhen; Weiss, James N.; Qu, Zhilin

2015-01-01

In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the mechanisms of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in “orphaned” RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. PMID:25450613

T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

PubMed

Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

2015-02-01

In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.

A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor.

PubMed

Cui, Yanfang; Tae, Han-Shen; Norris, Nicole C; Karunasekara, Yamuna; Pouliquin, Pierre; Board, Philip G; Dulhunty, Angela F; Casarotto, Marco G

2009-03-01

The II-III loop of the dihydropyridine receptor (DHPR) alpha(1s) subunit is a modulator of the ryanodine receptor (RyR1) Ca(2+) release channel in vitro and is essential for skeletal muscle contraction in vivo. Despite its importance, the structure of this loop has not been reported. We have investigated its structure using a suite of NMR techniques which revealed that the DHPR II-III loop is an intrinsically unstructured protein (IUP) and as such belongs to a burgeoning structural class of functionally important proteins. The loop does not possess a stable tertiary fold: it is highly flexible, with a strong N-terminal helix followed by nascent helical/turn elements and unstructured segments. Its residual structure is loosely globular with the N and C termini in close proximity. The unstructured nature of the II-III loop may allow it to easily modify its interaction with RyR1 following a surface action potential and thus initiate rapid Ca(2+) release and contraction. The in vitro binding partner for the II-III was investigated. The II-III loop interacts with the second of three structurally distinct SPRY domains in RyR1, whose function is unknown. This interaction occurs through two preformed N-terminal alpha-helical regions and a C-terminal hydrophobic element. The A peptide corresponding to the helical N-terminal region is a common probe of RyR function and binds to the same SPRY domain as the full II-III loop. Thus the second SPRY domain is an in vitro binding site for the II-III loop. The possible in vivo role of this region is discussed.

Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor.

PubMed

Wolf, Insa M A; Diercks, Björn-Philipp; Gattkowski, Ellen; Czarniak, Frederik; Kempski, Jan; Werner, René; Schetelig, Daniel; Mittrücker, Hans-Willi; Schumacher, Valéa; von Osten, Manuel; Lodygin, Dimitri; Flügel, Alexander; Fliegert, Ralf; Guse, Andreas H

2015-10-13

The activation of T cells is the fundamental on switch for the adaptive immune system. Ca(2+) signaling is essential for T cell activation and starts as initial, short-lived, localized Ca(2+) signals. The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) forms rapidly upon T cell activation and stimulates early Ca(2+) signaling. We developed a high-resolution imaging technique using multiple fluorescent Ca(2+) indicator dyes to characterize these early signaling events and investigate the channels involved in NAADP-dependent Ca(2+) signals. In the first seconds of activation of either primary murine T cells or human Jurkat cells with beads coated with an antibody against CD3, we detected Ca(2+) signals with diameters close to the limit of detection and that were close to the activation site at the plasma membrane. In Jurkat cells in which the ryanodine receptor (RyR) was knocked down or in primary T cells from RyR1(-/-) mice, either these early Ca(2+) signals were not detected or the number of signals was markedly reduced. Local Ca(2+) signals observed within 20 ms upon microinjection of Jurkat cells with NAADP were also sensitive to RyR knockdown. In contrast, TRPM2 (transient receptor potential channel, subtype melastatin 2), a potential NAADP target channel, was not required for the formation of initial Ca(2+) signals in primary T cells. Thus, through our high-resolution imaging method, we characterized early Ca(2+) release events in T cells and obtained evidence for the involvement of RyR and NAADP in such signals. Copyright © 2015, American Association for the Advancement of Science.

Different oxidative status and expression of calcium channel components in stress-induced dysfunctional chicken muscle.

PubMed

Xing, T; Zhao, X; Wang, P; Chen, H; Xu, X; Zhou, G

2017-04-01

The objective of this study was to assess the effects of transport stress at high ambient temperatures on the oxidation status and the expression of essential elements responsible for the Ca transport (sarco- (endo-) plasmic reticulum Ca-ATPase (SERCA1) and the ryanodine receptor (RyR) in (PM) muscles of broilers. Briefly, Arbor Acres broiler chickens ( = 112) were randomly categorized into 2 treatments: unstressed control (C) and 0.5 h transport (T). Each treatment consisted of 8 replicates of 7 birds each. Birds were transported according to a designed protocol. PM muscle samples in T group were collected and classified as normal (T-NOR) or pale, soft, and exudative-like (T-PSE) using meat quality parameters. The results indicated that production of corticosterone (CORT) and reactive oxygen species (ROS) increased significantly after transportation ( < 0.05). Thiobarbituric acid reactive substance values and carbonyl contents increased significantly in the T group ( < 0.05). Moreover, the extent of lipid peroxidation and protein oxidation was more severe in the T-PSE group compared to the T-NOR group ( < 0.05). The mRNA and protein expression of SERCA1 and αRyR increased in the T-NOR group but decreased significantly in the T-PSE group compared to the CON group ( < 0.05). The mRNA expression of βRyR was found to be enhanced in the T-NOR group compared to the CON group, whereas there was no difference in the T-PSE group ( < 0.05). The results indicate that short-distance transport of broilers affects their physiological responses and biochemical changes which may lead to different oxidative states and, importantly, to different expressions of SERCA and RyR. These induced changes in abnormal sarcoplasmic Ca homeostasis have significant implications for the development of PSE-like meat.

Disbalance of calcium regulation-related genes in broiler hearts induced by selenium deficiency.

PubMed

Zhang, Ziwei; Liu, Man; Guan, Zhenqiong; Yang, Jie; Liu, Zhonghua; Xu, Shiwen

2017-06-01

Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in broilers. Our objective was to investigate the effects of Se deficiency on Ca regulation-related genes in broiler hearts. In the present study, 1-day-old broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined the mRNA expression levels of 15 Ca regulation-related genes (ITPR 1, ITPR 2, ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, stromal interacting molecule 1, ORAI1, calmodulin (CaLM) and calreticulin (CRT) in broiler hearts. Then, Kyoto Encyclopedia of Genes and Genomes analysis, protein-protein interactions (PPI) analysis and correlation analysis were performed to analyse the relationships between these genes. The results showed that the mRNA expression levels of ITPR 1, ITPR 2, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, CaLM and CRT were generally decreased by Se deficiency, while mRNA expression levels of TRPC1, TRPC3, stromal interacting molecule 1, ORAI1 and ITPR3 were increased by Se deficiency. Kyoto Encyclopedia of Genes and Genomes and PPI analysis showed that these Ca regulation-related genes are involved in the Ca signalling pathway and a total of 15 PPIs with a combined score of >0.4 were obtained. In conclusion, the results demonstrated that Se deficiency might cause heart injury via modulating the Ca-related pathway genes, and then induce Ca 2+ overload in the heart of broilers.

STEREO observations of HD90386 (RX Sex): a δ-Scuti or a hybrid star?

NASA Astrophysics Data System (ADS)

Ozuyar, D.; Stevens, I. R.; Whittaker, G.; Sangaralingam, V.

2016-04-01

HD90386 is a rarely studied bright A2V type δ Scuti star (V = 6.66 mag). It displays short-term light curve variations which are originated due to either a beating phenomenon or a non-periodic variation. In this paper, we presented high-precision photometric data of HD90386 taken by the STEREO satellite between 2007 and 2011 to shed light on its internal structure and evolution stage. From the frequency analysis of the four-year data, we detected that HD90386 had at least six different frequencies between 1 and 15 c d-1. The most dominant frequencies were found at around 10.25258 c d-1 (A ∼ 1.92 mmag) and 12.40076 c d-1 (A ∼ 0.61 mmag). Based on the ratio between these frequencies, the star was considered as an overtone pulsator. The variation in pulsation period over 35 years was calculated to be dP/Pdt = 5.39(2) x 10-3 yr-1. Other variabilities at around 1.0 c d-1 in the amplitude spectrum of HD90386 were also discussed. In order to explain these variabilities, possible rotational effects and γ Dor type variations were focused. Consequently, depending on the rotation velocity of HD90386, we speculated that these changes might be related to γ Dor type high-order g-modes shifted to the higher frequencies and that HD90386 might be a hybrid star.

The Delta Scuti star 38 Eri from the ground and from space

NASA Astrophysics Data System (ADS)

Paparó, M.; Kolláth, Z.; Shobbrook, R. R.; Matthews, J. M.; Antoci, V.; Benkő, J. M.; Park, N.-K.; Mirtorabi, M. T.; Luedeke, K.; Kusakin, A.; Bognár, Zs; Sódor, Á.; García-Hernández, A.; Pe na, J. H.; Kuschnig, R.; Moffat, A. F. J.; Rowe, J.; Rucinski, S. M.; Sasselov, D.; Weiss, W. W.

2018-04-01

We present and discuss the pulsational characteristics of the Delta Scuti star 38 Eri from photometric data obtained at two widely spaced epochs, partly from the ground (1998) and partly from space (MOST, 2011). We found 18 frequencies resolving the discrepancy among the previously published frequencies. Some of the frequencies appeared with different relative amplitudes at two epochs, however, we carried out investigation for amplitude variability for only the MOST data. Amplitude variability was found for one of three frequencies that satisfy the necessary frequency criteria for linear-combination or resonant-mode coupling. Checking the criteria of beating and resonant-mode coupling we excluded them as possible reason for amplitude variability. The two recently developed methods of rotational-splitting and sequence-search were applied to find regular spacings based only on frequencies. Doublets or incomplete multiplets with l = 1, 2 and 3 were found in the rotational splitting search. In the sequence search method we identified four sequences. The averaged spacing, probably a combination of the large separation and the rotational frequency, is 1.724 ± 0.092 d-1. Using the spacing and the scaling relation \\bar{ρ }= [0.0394, 0.0554] gcm-3 was derived. The shift of the sequences proved to be the integer multiple of the rotational splitting spacing. Using the precise MOST frequencies and multi-colour photometry in a hybrid way, we identified four modes with l = 1, two modes with l = 2, two modes with l = 3, and two modes as l = 0 radial modes.

ROTATIONALLY MODULATED g-MODES IN THE RAPIDLY ROTATING {delta} SCUTI STAR RASALHAGUE ({alpha} OPHIUCHI)

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

Monnier, J. D.; Che, X.; Townsend, R. H. D.

2010-12-10

Despite a century of remarkable progress in understanding stellar interiors, we know surprisingly little about the inner workings of stars spinning near their critical limit. New interferometric imaging of these so-called rapid rotators combined with breakthroughs in asteroseismology promise to lift this veil and probe the strongly latitude-dependent photospheric characteristics and even reveal the internal angular momentum distribution of these luminous objects. Here, we report the first high-precision photometry on the low-amplitude {delta} Scuti variable star Rasalhague ({alpha} Oph, A5IV, 2.18 M{sub sun}, {omega}/{omega}{sub c}{approx}0.88) based on 30 continuous days of monitoring using the MOST satellite. We have identified 57more » {+-} 1 distinct pulsation modes above a stochastic granulation spectrum with a cutoff of {approx}26 cycles day{sup -1}. Remarkably, we have also discovered that the fast rotation period of 14.5 hr modulates low-frequency modes (1-10 day periods) that we identify as a rich family of g-modes (|m| up to 7). The spacing of the g-modes is surprisingly linear considering Coriolis forces are expected to strongly distort the mode spectrum, suggesting we are seeing prograde 'equatorial Kelvin' waves (modes l = m). We emphasize the unique aspects of Rasalhague motivating future detailed asteroseismic modeling-a source with a precisely measured parallax distance, photospheric oblateness, latitude temperature structure, and whose low-mass companion provides an astrometric orbit for precise mass determinations.« less

A Genetic Interaction Screen for Breast Cancer Progression Driver Genes

DTIC Science & Technology

2014-08-01

M D A -M B -2 3 1 M D A -M B -4 3 6 N o rm a l p r im a ry B re a s t C e lls P r im a ry T N B C KEY RESEARCH ACCOMPLISHMENTS: • Screening PB...GRANT NUMBER W81XWH-12-1-0082 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER Tian Xu, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail...tian.xu@yale.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Yale

76 FR 26431 - Medicare Program; Inpatient Psychiatric Facilities Prospective Payment System-Update for Rate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

...This final rule updates the prospective payment rates for Medicare inpatient hospital services provided by inpatient psychiatric facilities (IPFs) for discharges occurring during the rate year (RY) beginning July 1, 2011 through September 30, 2012. The final rule also changes the IPF prospective payment system (PPS) payment rate update period to a RY that coincides with a fiscal year (FY). In addition, the rule implements policy changes affecting the IPF PPS teaching adjustment. It also rebases and revises the Rehabilitation, Psychiatric, and Long-Term Care (RPL) market basket, and makes some clarifications and corrections to terminology and regulations text.

Military Police Authority over Civilians. They look like Police, They Act like Police, But Are They Police

DTIC Science & Technology

1978-06-09

ndsc.t.=. accomplishing tZheize-r missLon toantaa n aw W-c order on m a- ry instaa- tiors. Tne proposed sta t=rv l -nguage -D -e d di dnce b" specifically...Military Moie.........10 Loss of Court-Matial jurisdiction Over Civilian4s . . . 10 Prohibitions Against Execution of Civil l ~aws by Soldiers...have only the authority of - a Ti---k---- 3 10a~~z~ ~ry c t ens- to er c!tizes onli nr ci e in law enforcement against other citizens. 1fT. irr l ’fL

Biodegradation of Mordant orange-1 using newly isolated strain Trichoderma harzianum RY44 and its metabolite appraisal.

PubMed

Hadibarata, Tony; Syafiuddin, Achmad; Al-Dhabaan, Fahad A; Elshikh, Mohamed Soliman; Rubiyatno

2018-05-01

Herein, we systematically reported the capability of T. harzianum RY44 for decolorization of Mordant orange-1. The fungi strains were isolated from the Universiti Teknologi Malaysia tropical rain forest. For initial screening, the decolorization was conducted using 50 strains of the fungi for 20 days incubation time and the best performance was selected. Then, the decolorization capability and fungal biomass were evaluated using different dye concentrations, namely, 0, 50, 75 and 100 ppm. Effects of the carbon sources (fructose, glucose, and galactose), nitrogen sources (ammonium nitrate, ammonium sulfate and yeast extract), surfactant (tween 80), aromatic compounds (benzoic acid, catechol and salicylic acid), and pH on the decolorization efficiency were examined. This study has found that the employed carbon sources, nitrogen sources, and aromatic compounds strongly enhance the decolorization efficiency. In addition, increasing the surfactant volume and pH generally decreased the decolorization efficiencies from 19.5 to 9.0% and 81.7 to 60.5%, respectively. In the mechanism philosophy, the present work has found that Mordant orange-1 were initially degraded by T. harzianum RY44 to benzoic acid and finally transformed into salicylic acid.

Novel mutations and mutation combinations of ryanodine receptor in a chlorantraniliprole resistant population of Plutella xylostella (L.)

PubMed Central

Guo, Lei; Liang, Pei; Zhou, Xuguo; Gao, Xiwu

2014-01-01

A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. PMID:25377064

INVESTIGATING PLANET FORMATION IN CIRCUMSTELLAR DISKS: CARMA OBSERVATIONS OF RY Tau AND DG Tau

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

Isella, Andrea; Carpenter, John M.; Sargent, Anneila I., E-mail: isella@astro.caltech.ed

2010-05-10

We present CARMA observations of the thermal dust emission from the circumstellar disks around the young stars RY Tau and DG Tau at wavelengths of 1.3 mm and 2.8 mm. The angular resolution of the maps is as high as 0.''15, or 20 AU at the distance of the Taurus cloud, which is a factor of 2 higher than has been achieved to date at these wavelengths. The unprecedented detail of the resulting disk images enables us to address three important questions related to the formation of planets. (1) What is the radial distribution of the circumstellar dust? (2) Doesmore » the dust emission show any indication of gaps that might signify the presence of (proto-)planets? (3) Do the dust properties depend on the orbital radius? We find that modeling the disk surface density in terms of either a classical power law or the similarity solution for viscous disk evolution reproduces the observations well. Both models constrain the surface density between 15 and 50 AU to within 30% for a given dust opacity. Outside this range, the densities inferred from the two models differ by almost an order of magnitude. The 1.3 mm image from RY Tau shows two peaks separated by 0.''2 with a decline in the dust emission toward the stellar position, which is significant at about 2{sigma}-4{sigma}. For both RY Tau and DG Tau, the dust emission at radii larger than 15 AU displays no significant deviation from an unperturbed viscous disk model. In particular, no radial gaps in the dust distribution are detected. Under reasonable assumptions, we exclude the presence of planets more massive than 5 M{sub J} orbiting either star at distances between about 10 and 60 AU, unless such a planet is so young that there has been insufficient time to open a gap in the disk surface density. The radial variation of the dust opacity slope, {beta}, was investigated by comparing the 1.3 mm and 2.8 mm observations. We find mean values of {beta} of 0.5 and 0.7 for DG Tau and RY Tau, respectively. Variations in {beta} are smaller than {Delta}{beta} = 0.7 between 20 and 70 AU. These results confirm that the circumstellar dust throughout these disks differs significantly from dust in the interstellar medium.« less

Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

PubMed Central

Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

2016-01-01

Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether decay of Ca waves, biphasic or monophasic, occurs. PMID:26537441

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke

PubMed Central

Liu, Rui; Zhou, Zi-yi; Chen, Yi-bei; Li, Jia-li; Yu, Wei-bang; Chen, Xin-meng; Zhao, Min; Zhao, Yuan-qi; Cai, Ye-feng; Jin, Jing; Huang, Min

2016-01-01

Aim: There is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. Methods: A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4*1G (rs2242480), CYP2C19*2 (rs4244285) and P2RY12 (rs2046934) were genotyped. Results: The CR rate in this population was 36%. The CYP2C19*2 variant was a risk factor for CR (*2/*2+wt/*2 vs wt/wt, OR: 2.366, 95% CI: 1.180–4.741, P=0.014), whereas the CYP3A4*1G variant had a protective effect on CR (*1/*1 vs *1G/*1G+*1/*1G, OR: 2.360, 95% CI: 1.247–4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286–0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191–0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022). Conclusion: The individuals with both the CYP2C19*2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4*1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke. PMID:27133299

Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO

PubMed Central

Sun, Junhui; Xin, Chunlin; Eu, Jerry P.; Stamler, Jonathan S.; Meissner, Gerhard

2001-01-01

We have shown previously that at physiologically relevant oxygen tension (pO2 ≈ 10 mmHg), NO S-nitrosylates 1 of ≈50 free cysteines per ryanodine receptor 1 (RyR1) subunit and transduces a calcium-sensitizing effect on the channel by means of calmodulin (CaM). It has been suggested that cysteine-3635 is part of a CaM-binding domain, and its reactivity is attenuated by CaM [Porter Moore, C., Zhang, J. Z., Hamilton, S. L. (1999) J. Biol. Chem. 274, 36831–36834]. Therefore, we tested the hypothesis that the effect of NO was mediated by C3635. The full-length RyR1 single-site C3635A mutant was generated and expressed in HEK293 cells. The mutation resulted in the loss of CaM-dependent NO modulation of channel activity and reduced S-nitrosylation by NO to background levels but did not affect NO-independent channel modulation by CaM or the redox sensitivity of the channel to O2 and glutathione. Our results reveal that different cysteines within the channel have been adapted to serve in nitrosative and oxidative responses, and that S-nitrosylation of the cysteine-containing CaM-binding domain underlies the mechanism of CaM-dependent regulation of RyR1 by NO. PMID:11562475

Carvedilol inhibits cADPR- and IP3-induced Ca2+ release.

PubMed

Morgan, Anthony J; Bampali, Konstantina; Ruas, Margarida; Factor, Cailley; Back, Thomas G; Chen, S R Wayne; Galione, Antony

2016-06-01

Spontaneous Ca 2+ waves, also termed store-overload-induced Ca 2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca 2+ . Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca 2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca 2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca 2+ release by caffeine. These results are consistent with cADPR releasing Ca 2+ in sea urchin eggs by sensitizing RyRs to Ca 2+ involving a luminal Ca 2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP 3 )-induced Ca 2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca 2+ release channels.

Multi-modal Patient Cohort Identification from EEG Report and Signal Data

PubMed Central

Goodwin, Travis R.; Harabagiu, Sanda M.

2016-01-01

Clinical electroencephalography (EEG) is the most important investigation in the diagnosis and management of epilepsies. An EEG records the electrical activity along the scalp and measures spontaneous electrical activity of the brain. Because the EEG signal is complex, its interpretation is known to produce moderate inter-observer agreement among neurologists. This problem can be addressed by providing clinical experts with the ability to automatically retrieve similar EEG signals and EEG reports through a patient cohort retrieval system operating on a vast archive of EEG data. In this paper, we present a multi-modal EEG patient cohort retrieval system called MERCuRY which leverages the heterogeneous nature of EEG data by processing both the clinical narratives from EEG reports as well as the raw electrode potentials derived from the recorded EEG signal data. At the core of MERCuRY is a novel multimodal clinical indexing scheme which relies on EEG data representations obtained through deep learning. The index is used by two clinical relevance models that we have generated for identifying patient cohorts satisfying the inclusion and exclusion criteria expressed in natural language queries. Evaluations of the MERCuRY system measured the relevance of the patient cohorts, obtaining MAP scores of 69.87% and a NDCG of 83.21%. PMID:28269938

Metal-rich RRc Stars in the Carnegie RR Lyrae Survey

NASA Astrophysics Data System (ADS)

Sneden, Christopher; Preston, George W.; Kollmeier, Juna A.; Crane, Jeffrey D.; Morrell, Nidia; Prieto, José L.; Shectman, Stephen A.; Skowron, Dorota M.; Thompson, Ian B.

2018-01-01

We describe and employ a stacking procedure to investigate abundances derived from the low signal-to-noise ratio spectra obtained in the Carnegie RR Lyrae Survey (CARRS). We find iron metallicities that extend from [Fe/H] ∼ ‑2.5 to values at least as large as [Fe/H] ∼ ‑0.5 in the 274-spectrum CARRS RRc data set. We consider RRc sample contamination by high amplitude solar metallicity δ Scuti stars (HADS) at periods less than 0.3 days, where photometric discrimination between RRc and δ Scuti stars has proven to be problematic. We offer a spectroscopic discriminant, the well-marked overabundance of heavy elements, principally [Ba/H], that is a common, if not universal, characteristic of HADS of all periods and axial rotations. No bona fide RRc stars known to us have verified heavy-element overabundances. Three out of 34 stars in our sample with [Fe/H] > ‑0.7 exhibit anomalously strong features of Sr, Y, Zr, Ba, and many rare earths. However, carbon is not enhanced in these three stars, and we conclude that their elevated n-capture abundances have not been generated in interior neutron-capture nucleosynthesis. Contamination by HADS appears to be unimportant, and metal-rich RRc stars occur in approximately the same proportion in the Galactic field as do metal-rich RRab stars. An apparent dearth of metal-rich RRc is probably a statistical fluke. Finally, we show that RRc stars have a similar inverse period–metallicity relationship as has been found for RRab stars.

The Delta Scuti star 38 Eri from the ground and from space

NASA Astrophysics Data System (ADS)

Paparó, M.; Kolláth, Z.; Shobbrook, R. R.; Matthews, J. M.; Antoci, V.; Benkő, J. M.; Park, N.-K.; Mirtorabi, M. T.; Luedeke, K.; Kusakin, A.; Bognár, Zs; Sódor, Á.; García-Hernández, A.; Peña, J. H.; Kuschnig, R.; Moffat, A. F. J.; Rowe, J.; Rucinski, S. M.; Sasselov, D.; Weiss, W. W.

2018-07-01

We present and discuss the pulsational characteristics of the Delta Scuti star 38 Eri from photometric data obtained at two widely spaced epochs, partly from the ground (1998) and partly from space (MOST, 2011). We found 18 frequencies resolving the discrepancy among the previously published frequencies. Some of the frequencies appeared with different relative amplitudes at two epochs, however, we carried out investigation for amplitude variability for only the MOST (Microvariability and Oscillation of STars) data. Amplitude variability was found for one of the three frequencies that satisfy the necessary frequency criteria for linear-combination or resonant-mode coupling. Checking the criteria of beating and resonant-mode coupling we excluded them as possible reason for amplitude variability. The two recently developed methods of rotational splitting and sequence search were applied to find regular spacings based only on frequencies. Doublets or incomplete multiplets with l = 1, 2, and 3 were found in the rotational splitting search. In the sequence search method we identified four sequences. The averaged spacing, probably a combination of the large separation and the rotational frequency, is 1.724 ± 0.092 d-1. Using the spacing and the scaling relation \\bar{ρ}= [0.0394, 0.0554] g cm-3 was derived. The shift of the sequences proved to be the integer multiple of the rotational splitting spacing. Using the precise MOST frequencies and multicolour photometry in a hybrid way, we identified four modes with l = 1, two modes with l = 2, two modes with l = 3, and two modes as l = 0 radial modes.

Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks

PubMed Central

Gomez-Hurtado, Nieves; Boczek, Nicole J.; Kryshtal, Dmytro O.; Johnson, Christopher N.; Sun, Jennifer; Nitu, Florentin R.; Cornea, Razvan L.; Chazin, Walter J.; Calvert, Melissa L.; Tester, David J.; Ackerman, Michael J.; Knollmann, Bjorn C.

2016-01-01

Background Calmodulin (CaM) mutations are associated with severe forms of long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). We recently reported that CaM mutations were found in 13% of genotype-negative LQTS patients, but the prevalence of CaM mutations in genotype-negative CPVT patients is unknown. Here, we identify and characterize CaM mutations in 12 patients with genotype-negative but clinically-diagnosed CPVT. Methods and Results Mutational analysis of CALM1, CALM2 and CALM3 coding regions, in vitro measurement of CaM-Ca2+ (Ca) binding affinity, RyR2-CaM binding, Ca handling, L-type Ca current (LTCC) and action potential duration (APD). We identified a novel CaM mutation – A103V – in CALM3 in 1 of 12 patients (8%), a female who experienced episodes of exertion-induced syncope since age 10, had normal QT interval, and displayed ventricular ectopy during stress testing consistent with CPVT. A103V modestly lowered CaM Ca-binding affinity (3-fold reduction vs WT-CaM), but did not alter CaM binding to RyR2. In permeabilized cardiomyocytes, A103V-CaM (100 nM) promoted spontaneous Ca wave and spark activity, a cellular phenotype of RyR2 activation. Even a 1:3 mixture of A103V-CaM:WT-CaM activated Ca waves, demonstrating functional dominance. Compared to LQTS D96V-CaM, A103V-CaM had significantly less effects on LTCC inactivation and APD, and caused delayed after depolarizations (DADs) and triggered beats in intact cardiomyocytes. Conclusions We discovered a novel CPVT mutation in the CALM3 gene that shares functional characteristics with established CPVT-associated mutations in CALM1. A small proportion of A103V-CaM is sufficient to evoke arrhythmogenic Ca disturbances via RyR2 dysregulation, which explains the autosomal dominant inheritance. PMID:27516456

Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration.

PubMed

Orem, Ben C; Pelisch, Nicolas; Williams, Joshua; Nally, Jacqueline M; Stirling, David P

2017-10-01

Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca 2+ store mediated intra-axonal Ca 2+ release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model. Ascending spinal cord dorsal column axons that express YFP were severed using an 800 nm laser pulse while being imaged continuously using two-photon excitation microscopy. We inhibited two major intra-axonal Ca 2+ store channels, ryanodine receptors (RyR) and IP 3 R, with ryanodine or 2-APB, respectively, to individually determine their role in axonal dieback and secondary axonal degeneration. Each antagonist was dissolved in artificial CSF and applied 1h post-injury alone or in combination, and continuously perfused for the remainder of the imaging session. Initially following LiSCI, transected axons retracted equal distances both distal and proximal to the lesion. However, by 4h after injury, the distal axonal segments that are destined for Wallerian degeneration had significantly retracted further than their proximal counterparts. We also found that targeting either RyR or IP 3 R using pharmacological and genetic approaches significantly reduced proximal axonal dieback and "bystander" secondary degeneration of axons compared to vehicle controls at 6h post-injury. Combined treatment effects on secondary axonal degeneration were similar to either drug in isolation. Together, these results suggest that intra-axonal Ca 2+ store mediated Ca 2+ release through RyR or IP 3 R contributes to secondary axonal degeneration following SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

PubMed

Li, Mengye; Hothi, Sandeep S; Salvage, Samantha C; Jeevaratnam, Kamalan; Grace, Andrew A; Huang, Christopher L-H

2017-06-01

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P<.05). However, dantrolene, whether alone (0 of 10 and 1 of 13) or combined with 8-CPT (0 of 10 and 0 of 13) did not increase VT incidence relative to those observed in untreated hearts (P>.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV. © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

Mutation-linked, excessively tight interaction between the calmodulin binding domain and the C-terminal domain of the cardiac ryanodine receptor as a novel cause of catecholaminergic polymorphic ventricular tachycardia.

PubMed

Nishimura, Shigehiko; Yamamoto, Takeshi; Nakamura, Yoshihide; Kohno, Michiaki; Hamada, Yoriomi; Sufu, Yoko; Fukui, Go; Nanno, Takuma; Ishiguchi, Hironori; Kato, Takayoshi; Xu, Xiaojuan; Ono, Makoto; Oda, Tetsuro; Okuda, Shinichi; Kobayashi, Shigeki; Yano, Masafumi

2018-06-01

Ryanodine receptor (RyR2) is known to be a causal gene of catecholaminergic polymorphic ventricular tachycardia (CPVT), an important inherited disease. Some of the human CPVT-associated mutations have been found in a domain (4026-4172) that has EF hand motifs, the so-called calmodulin (CaM)-like domain (CaMLD). The purpose of this study was to investigate the underlying mechanism by which CPVT is induced by a mutation at CaMLD. A new N4103K/+ knock-in (KI) mice model was generated. Sustained ventricular tachycardia was frequently observed after infusion of caffeine plus epinephrine in KI mice. Endogenous CaM bound to RyR2 decreased even at baseline in isolated KI cardiomyocytes. Ca 2+ spark frequency (CaSpF) was much higher in KI cells than in wild-type cells. Addition of GSH-CaM (higher affinity CaM to RyR2) significantly decreased CaSpF. In response to isoproterenol, spontaneous Ca 2+ transient (SCaT) was frequently observed in intact KI cells. Incorporation of GSH-CaM into intact KI cells using a protein delivery kit decreased SCaT significantly. An assay using a quartz crystal microbalance technique revealed that mutated CaMLD peptide showed higher binding affinity to CaM binding domain (CaMBD) peptide. In the N4103K mutant, CaM binding affinity to RyR2 was significantly reduced regardless of beta-adrenergic stimulation. We found that this was caused by an abnormally tight interaction between CaMBD and mutated CaM-like domain (N4103K-CaMBD). Thus, CaMBD-CaMLD interaction may be a novel therapeutic target for treatment of lethal arrhythmia. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Involvement of plasma membrane Ca2+ channels, IP3 receptors, and ryanodine receptors in the generation of spontaneous rhythmic contractions of the cricket lateral oviduct.

PubMed

Tamashiro, Hirotake; Yoshino, Masami

2014-12-01

In the present study, the isolated cricket (Gryllus bimaculatus) lateral oviduct exhibited spontaneous rhythmic contractions (SRCs) with a frequency of 0.29±0.009 Hz (n=43) and an amplitude of 14.6±1.25 mg (n=29). SRCs completely disappeared following removal of extracellular Ca2+ using a solution containing 5mM EGTA. Application of the non-specific Ca2+ channel blockers Co2+, Ni2+, and Cd2+ also decreased both the frequency and amplitude of SRCs in dose-dependent manners, suggesting that Ca2+ entry through plasma membrane Ca2+ channels is essential for the generation of SRCs. Application of ryanodine (30 μM), which depletes intracellular Ca2+ by locking ryanodine receptor (RyR)-Ca2+ channels in an open state, gradually reduced the frequency and amplitude of SRCs. A RyR antagonist, tetracaine, reduced both the frequency and amplitude of SRCs, whereas a RyR activator, caffeine, increased the frequency of SRCs with a subsequent increase in basal tonus, indicating that RyRs are essential for generating SRCs. To further investigate the involvement of phospholipase C (PLC) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in SRCs, we examined the effect of a PLC inhibitor, U73122, and an IP3R antagonist, 2-aminoethoxydiphenyl borate (2-APB), on SRCs. Separately, U73122 (10 μM) and 2-APB (30-50 μM) both significantly reduced the amplitude of SRCs with little effect on their frequency, further indicating that the PLC/IP3R signaling pathway is fundamental to the modulation of the amplitude of SRCs. A hypotonic-induced increase in the frequency and amplitude of SRCs and a hypertonic-induced decrease in the frequency and amplitude of SRCs indicated that mechanical stretch of the lateral oviduct is involved in the generation of SRCs. The sarcoplasmic reticulum Ca2+-pump ATPase inhibitors thapsigargin and cyclopiazonic acid impaired or suppressed the relaxation phase of SRCs. Taken together, the present results indicate that Ca2+ influx through plasma membrane Ca2+ channels and Ca2+ release from RyRs play an essential role in pacing SRCs and that Ca2+ release from IP3Rs may play a role in modulating the amplitude of SRCs, probably via activation of PLC. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel mechanism of tandem activation of ryanodine receptors by cytosolic and SR luminal Ca2+ during excitation-contraction coupling in atrial myocytes.

PubMed

Maxwell, Joshua T; Blatter, Lothar A

2017-06-15

In atrial myocytes excitation-contraction coupling is strikingly different from ventricle because atrial myocytes lack a transverse tubule membrane system: Ca 2+ release starts in the cell periphery and propagates towards the cell centre by Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum (SR) Ca 2+ store. The cytosolic Ca 2+ sensitivity of the ryanodine receptor (RyRs) Ca 2+ release channel is low and it is unclear how Ca 2+ release can be activated in the interior of atrial cells. Simultaneous confocal imaging of cytosolic and intra-SR calcium revealed a transient elevation of store Ca 2+ that we termed 'Ca 2+ sensitization signal'. We propose a novel paradigm of atrial ECC that is based on tandem activation of the RyRs by cytosolic and luminal Ca 2+ through a 'fire-diffuse-uptake-fire' (or FDUF) mechanism: Ca 2+ uptake by SR Ca 2+ pumps at the propagation front elevates Ca 2+ inside the SR locally, leading to luminal RyR sensitization and lowering of the cytosolic Ca 2+ activation threshold. In atrial myocytes Ca 2+ release during excitation-contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca 2+ store into the peripheral subsarcolemmnal junctional (j-SR) and the much more abundant central non-junctional (nj-SR) SR. Action potential (AP)-induced Ca 2+ entry activates Ca 2+ -induced Ca 2+ release (CICR) from j-SR ryanodine receptor (RyR) Ca 2+ release channels. Peripheral elevation of [Ca 2+ ] i initiates CICR from nj-SR and sustains propagation of CICR to the cell centre. Simultaneous confocal measurements of cytosolic ([Ca 2+ ] i ; with the fluorescent Ca 2+ indicator rhod-2) and intra-SR ([Ca 2+ ] SR ; fluo-5N) Ca 2+ in rabbit atrial myocytes revealed that Ca 2+ release from j-SR resulted in a cytosolic Ca 2+ transient of higher amplitude compared to release from nj-SR; however, the degree of depletion of j-SR [Ca 2+ ] SR was smaller than nj-SR [Ca 2+ ] SR . Similarly, Ca 2+ signals from individual release sites of the j-SR showed a larger cytosolic amplitude (Ca 2+ sparks) but smaller depletion (Ca 2+ blinks) than release from nj-SR. During AP-induced Ca 2+ release the rise of [Ca 2+ ] i detected at individual release sites of the nj-SR preceded the depletion of [Ca 2+ ] SR , and during this latency period a transient elevation of [Ca 2+ ] SR occurred. We propose that Ca 2+ release from nj-SR is activated by cytosolic and luminal Ca 2+ (tandem RyR activation) via a novel 'fire-diffuse-uptake-fire' (FDUF) mechanism. This novel paradigm of atrial ECC predicts that Ca 2+ uptake by sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA) at the propagation front elevates local [Ca 2+ ] SR , leading to luminal RyR sensitization and lowering of the activation threshold for cytosolic CICR. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

One new species and three new records of Chrysis Linnaeus from China (Hymenoptera, Chrysididae)

PubMed Central

Rosa, Paolo; Wei, Na-sen; Xu, Zai-fu

2017-01-01

Abstract Four Chinese Chrysis species-groups, the antennata, capitalis, elegans, and maculicornis species-groups, are discussed. Chrysis lapislazulina Rosa & Xu, sp. n. is described in the elegans species-group; and three species, C. brachyceras Bischoff, 1910, C. subdistincta Linsenmaier, 1968 and C. yoshikawai Tsuneki, 1961, are reported for the first time from China in other species-groups. A new synonymy is proposed for C. ignifascia Mocsáry, 1893 = C. taiwana Tsuneki, 1970, syn. n. A short historical review of the elegans species-group is provided. C. goetheana Semenov, 1967 is transferred from the elegans species-group to the maculicornis species-group. C. mesochlora Mocsáry, 1893 is considered a nomen dubium. PMID:28769653

Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

PubMed

Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

2018-03-16

Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

Optical X-ray density of composite resin luting agents.

PubMed

Carracho, Helena G; da Silveira, Ivori D; Soares, Clarissa G; Paranhos, Maria Paula G; Júnior, Luiz Henrique Burnett; Spohr, Ana Maria

2011-01-01

This study verified the optical density of four composite resin luting agents - RelyX ARC (RY), Enforce (E), C&B Cement (CB) and Flow it (FI), at thicknesses of 2, 3, and 4 mm. The optical density of the luting agents was compared with that of enamel and dentin at the same thicknesses. Fifteen tooth crowns were embedded in PVC cylinders with self-cured acrylic resin. In addition, acrylic resin was poured into 5 PVC cylinders and four equidistant 5 mm diameter holes were prepared, with one luting material inserted in each. A laboratory cutting machine was used to prepare 4-, 3- and 2-mm thick slices of the tooth crowns and materials. Digital images were obtained with a Digora system. Three radiographs of each thickness were obtained, totalizing 135 radiographs of the crowns and 45 of the materials. Three readings were carried out on each radiograph: three in enamel, three in dentin and three in each material, totalizing 1350. According to Students t-test (p

Atomic Data and Spectral Line Intensities for Ca IX

NASA Technical Reports Server (NTRS)

Landi, E.; Bhatia, A. K.

2012-01-01

Electron impact collision strengths, energy levels, oscillator strengths and spontaneous radiative decay rates are calculated for Ca IX. We include in the calculations the 33 lowest configurations in the n = 3, 4, 5 complexes, corresponding to 283 fine structure levels in the 3l3l ', 3l4l'' and 3l4l''' configurations, where l,l' = s, p, d, l '' = s, p, d, f and l''' = s, p, d, f, g. Collision strengths are calculated at five incident energies for all transitions: 5.8, 13.6, 24.2, 38.6 and 57.9 Ry above the threshold of each transition. An additional energy, very close to the transition threshold, has been added, whose value is between 0.0055 Ry and 0.23 Ry depending on the levels involved. Calculations have been carried out using the Flexible Atomic Code and the distorted wave approximation. Excitation rate coefficients are calculated as a function of electron temperature by assuming a Maxwellian electron velocity distribution. Using the excitation rate coefficients and the radiative transition rates calculated in the present work, statistical equilibrium equations for level populations are solved at electron densities covering the 10(exp 8)-10(exp 14)/cubic cm range and at an electron temperature of log T(sub e)(K)=5.8, corresponding to the maximum abundance of Ca IX. Spectral line intensities are calculated, and their diagnostic relevance is discussed.

The role of complement in myasthenia gravis: serological evidence of complement consumption in vivo.

PubMed

Romi, Fredrik; Kristoffersen, Einar K; Aarli, Johan A; Gilhus, Nils Erik

2005-01-01

Antibodies to the acetylcholine receptor (AChR) titin and the ryanodine receptor (RyR) occur in myasthenia gravis (MG). These antibodies are capable of complement activation in vitro. The involvement of the complement system should cause consumption of complement components such as C3 and C4 in vivo. Complement components C3 and C4 were assayed in sera from 78 AChR antibody-positive MG patients and 52 healthy controls. Forty-eight of the patient sera contained titin antibodies as well, and 20 were also RyR antibody-positive. MG patients with AChR antibody concentrations above the median (11.2 nmol/l) had significantly lower mean C3 and C4 concentrations in serum compared to those with AChR antibody concentrations below the median. Titin antibody-positive MG patients, titin antibody-negative early-onset MG patients, titin antibody-negative late-onset MG patients, and controls had similar C3 and C4 concentrations. Nor did mean C3 and C4 concentrations differ in MG patients with RyR antibodies. Patients with severe MG (grades 4 and 5) had similar C3 and similar C4 levels compared to those with mild MG (grades 1 and 2). An increased in vivo complement consumption was detected in MG patients with high AChR antibody concentrations, unrelated to MG severity and non-AChR muscle antibodies.

[Effects of different winter cover crops on soil organic carbon in a double cropping rice paddy field.

PubMed

Tang, Hai Ming; Cheng, Kai Kai; Xiao, Xiao Ping; Tang, Wen Guang; Wang, Ke; Li, Chao; Zhang, Fan; Sun, Yu Tao

2017-02-01

In a double cropping rice field experiment, effects of five winter cover crops on the total organic carbon (TOC), active organic carbon (AOC), carbon pool management index (CPMI) and organic carbon storage were studied in three soil layers (0-5, 5-10 and 10-20 cm).Winter cover crops of ryegrass (Ry), Chinese milk vetch (Mv), potato (Po), and rape (Ra) between two rice crops were compared with fallow as control (CK). The results showed that the TOC and AOC contents under Ry, Mv, Po and Ra treatments were higher than those of CK in all three la-yers. Meanwhile, the TOC and AOC contents in Po treatment were higher than those of other treatments. Compared with CK, the AOC, activity index (AI), carbon pool index (CPI) and CPMI in the soil were improved through the recycling of winter cover crops straw. The AOC, AI, CPI and CPMI in the studied layers increased in order of Po>Mv>Ry>Ra>CK. The results indicated that the recycling of winter cover crops straw promoted the storage of SOC in the 0-20 cm soil profile as compared with CK. The strongest effect of the winter cover crops on the SOC storage occurred in Mv treatment, followed by Mv and Po treatments, and the SOC storage increased with the increasing soil depth.

Environmental Assessment for the Construction of Facilities in Support of the 343d Training Squadron, 37th Training Group, Security Forces Apprentice Course at JBSA-Camp Bullis, Texas

DTIC Science & Technology

2012-11-01

ai n un de r g ov er nm en ta l j ur is di ct io n as a m ili ta ry tr ai ni ng fa ci lit y, a nd th er ef or e no lo ng...n o ne w co ns tru ct io n or re no va tio n w ou ld o cc ur ; t he re fo re , n o im pa ct s o n ai r q ua lit y w ou ld oc cu r. Te m...po ra ry a nd m in or in cr ea se s i n ai r p ol lu

Pulsations and period variations of the δ Scuti star AN Lyncis in a possible three-body system

NASA Astrophysics Data System (ADS)

Li, Gang; Fu, Jianning; Su, Jie; Fox-Machado, Lester; Michel, Raul; Guo, Zhen; Liu, Jinzhong; Feng, Guojie

2018-01-01

Observations for the δ Scuti star AN Lyn have been made between 2008 and 2016 with the 85-cm telescope at Xinglong station of National Astronomical Observatories of China, the 84-cm telescope at SPM Observatory of Mexico and the Nanshan One metre Wide field Telescope of Xinjiang Observatory of China. Data in V in 50 nights and in R in 34 nights are obtained in total. The bi-site observations from both Xinglong Station and SPM Observatory in 2014 are analysed with Fourier Decomposition to detect pulsation frequencies. Two independent frequencies are resolved, including one non-radial mode. A number of stellar model tracks are constructed with the MESA code and the fit of frequencies leads to the best-fitting model with the stellar mass of M = 1.70 ± 0.05 M⊙, the metallicity abundance of Z = 0.020 ± 0.001, the age of 1.33 ± 0.01 billion years and the period change rate 1/P · dP/dt = 1.06 × 10-9 yr-1, locating the star at the evolutionary stage close to the terminal age main sequence. The O-C diagram provides the period change rate of (1/P)(dP/dt) = 4.5(8) × 10-7 yr-1. However, the period change rate calculated from the models is smaller in two orders than the one derived from the O-C diagram. Together with the sinusoidal function signature, the period variations are regarded to be dominated by the light-travel time effect of the orbital motion of a three-body system with two low-luminosity components, rather than the stellar evolutionary effect.

Visual Spectroscopy of R Scuti (Poster abstract)

NASA Astrophysics Data System (ADS)

Undreiu, L.; Chapman, A.

2015-06-01

(Abstract only) We are currently conducting a visual spectral analysis of the brightest known RV Tauri variable star, R Scuti. The goal of our undergraduate research project is to investigate this variable star's erratic nature by collecting spectra at different times in its cycle. Starting in late June of 2014 and proceeding into the following four months, we have monitored the alterations in the spectral characteristics that accompany the progression of R Sct's irregular cycle. During this time, we were given the opportunity to document the star's most recent descent from maximum brightness V~5 to a relatively deep minimum of V~7.5. Analysis of the data taken during the star's period of declining magnitude has provided us with several interesting findings that concur with the observations of more technically sophisticated studies. Following their collection, we compared our observations and findings with archived material in the hopes of facilitating a better understanding of the physical state of RV Tauri stars and the perplexing nature of their evolution. Although identification of the elements in the star's bright phase proved to be challenging, documenting clear absorption features in its fainter stage was far less difficult. As previously reported in similar studies, we identified prominent TiO molecular absorption bands near R Sct's faintest state, typical of mid-M spectral type stars. In addition to these TiO absorption lines, we report the presence of many more metallic lines in the spectral profiles obtained near star's minimum. Supportive of previously published hypotheses regarding the causation of its variability, we observed significant variation in the star's spectral characteristics throughout different phases of its cycle. We are hopeful that our observations will make a meaningful contribution to existing databases and help advance our collective understanding of RV Tauri stars and their evolutionary significance.

Cloning of human cDNAs for Apg-1 and Apg-2, members of the Hsp110 family, and chromosomal assignment of their genes.

PubMed

Nonoguchi, K; Itoh, K; Xue, J H; Tokuchi, H; Nishiyama, H; Kaneko, Y; Tatsumi, K; Okuno, H; Tomiwa, K; Fujita, J

1999-09-03

In mice, the Hsp110/SSE family is composed of the heat shock protein (Hsp)110/105, Apg-1 and Apg-2. In humans, however, only the Hsp110/105 homolog has been identified as a member, and two cDNAs, Hsp70RY and HS24/p52, potentially encoding proteins structurally similar to, but smaller than, mouse Apg-2 have been reported. To clarify the membership of Hsp110 family in humans, we isolated Apg-1 and Apg-2 cDNAs from a human testis cDNA library. The human Apg-1 was 100% and 91.8% identical in length and amino acid (aa) sequence, respectively, to mouse Apg-1. Human Apg-2 was one aa shorter than and 95.5% identical in sequence to mouse Apg-2. In ECV304, human endothelial cells Apg-1 but not Apg-2 transcripts were induced in 2 h by a temperature shift from 32 degrees C to 39 degrees C. As found in mice, the response was stronger than that to a 37-42 degrees C shift. The human Apg-1 and Apg-2 genes were mapped to the chromosomal loci 4q28 and 5q23.3-q31.1, respectively, by fluorescence in-situ hybridization. We isolated cDNA and genomic clones encompassing the region critical for the difference between Apg-2 and HS24/p52. Although the primer sets used were derived from the sequences common to both cDNAs, all cDNA and genomic clones corresponded to Apg-2. Using a similar approach, the relationship between Apg-2 and Hsp70RY was assessed, and no clone corresponding to Hsp70RY was obtained. These results demonstrated that the Hsp110 family consists of at least three members, Apg-1, Apg-2 and Hsp110 in humans as well as in mice. The significance of HS24/p52 and Hsp70RY cDNAs previously reported remains to be determined.

Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood.

PubMed

Schmäh, Juliane; Fedders, Birthe; Panzer-Grümayer, Renate; Fischer, Susanna; Zimmermann, Martin; Dagdan, Elif; Bens, Susanne; Schewe, Denis; Moericke, Anja; Alten, Julia; Bleckmann, Kirsten; Siebert, Reiner; Schrappe, Martin; Stanulla, Martin; Cario, Gunnar

2017-10-01

A high-level expression of the CRLF2 gene is frequent in precursor B-cell acute lymphoblastic leukemia (pB-ALL) and can be caused by different genetic aberrations. The presence of the most frequent alteration, the P2RY8/CRLF2 fusion, was shown to be associated with a high relapse incidence in children treated according to ALL-Berlin-Frankfurt-Münster (BFM) protocols, which is poorly understood. Moreover, the frequency of other alterations has not been systematically analyzed yet. CRLF2 mRNA expression and potential genetic aberrations causing a CRLF2 high expression were prospectively assessed in 1,105 patients treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)-BFM ALL 2009 protocol. Additionally, we determined copy number alterations in selected B-cell differentiation genes for all CRLF2 high-expressing pB-ALL cases, as well as JAK2 and CRLF2 mutations. A CRLF2 high expression was detected in 26/178 (15%) T-cell acute lymphoblastic leukemia (T-ALL) cases, 21 of them (81%) had been stratified as high-risk patients by treatment response. In pB-ALL, a CRLF2 high expression was determined in 91/927 (10%) cases; the P2RY8/CRLF2 rearrangement in 44/91 (48%) of them, supernumerary copies of CRLF2 in 18/91 (20%), and, notably, the IGH/CRLF2 translocation was detected in 16/91 (18%). Remarkably, 7 of 16 (44%) patients with IGH/CRLF2 translocation had already relapsed. P2RY8/CRLF2- and IGH/CRLF2-positive samples (70 and 94%, respectively) were characterized by a high frequency of additional deletions in B-cell differentiation genes such as IKZF1 or PAX5. Our data suggest that this high frequency of genetic aberrations in the context of a high CRLF2 expression could contribute to the high risk of relapse in P2RY8/CRLF2- and IGH/CRLF2-positive ALL. © 2017 Wiley Periodicals, Inc.

Microcolumn studies of dye adsorption onto manganese oxides modified diatomite.

PubMed

Al-Ghouti, M A; Khraisheh, M A M; Ahmad, M N; Allen, S J

2007-07-19

The method described here cannot fully replace the analysis of large columns by small test columns (microcolumns). The procedure, however, is suitable for speeding up the determination of adsorption parameters of dye onto the adsorbent and for speeding up the initial screening of a large adsorbent collection that can be tedious if a several adsorbents and adsorption conditions must be tested. The performance of methylene blue (MB), a basic dye, Cibacron reactive black (RB) and Cibacron reactive yellow (RY) was predicted in this way and the influence of initial dye concentration and other adsorption conditions on the adsorption behaviour were demonstrated. On the basis of the experimental results, it can be concluded that the adsorption of RY onto manganese oxides modified diatomite (MOMD) exhibited a characteristic "S" shape and can be simulated effectively by the Thomas model. It is shown that the adsorption capacity increased as the initial dye concentration increased. The increase in the dye uptake capacity with the increase of the adsorbent mass in the column was due to the increase in the surface area of adsorbent, which provided more binding sites for the adsorption. It is shown that the use of high flow rates reduced the time that RY in the solution is in contact with the MOMD, thus allowing less time for adsorption to occur, leading to an early breakthrough of RY. A rapid decrease in the column adsorption capacity with an increase in particle size with an average 56% reduction in capacity resulting from an increase in the particle size from 106-250 microm to 250-500 microm. The experimental data correlated well with calculated data using the Thomas equation and the bed depth-service time (BDST) equation. Therefore, it might be concluded that the Thomas equation and the BDST equations can produce accurate predication for variation of dye concentration, mass of the adsorbent, flow rate and particle size. In general, the values of adsorption isotherm capacity obtained in a batch system show the maximum values and are considerably higher than those obtained in a fixed-bed.

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.

Ryanodine receptors regulate arterial diameter and wall [Ca2+] in cerebral arteries of rat via Ca2+-dependent K+ channels

PubMed Central

Knot, Harm J; Standen, Nicholas B; Nelson, Mark T

1998-01-01

The effects of inhibitors of ryanodine-sensitive calcium release (RyR) channels in the sarcoplasmic reticulum (SR) and Ca2+-dependent potassium (KCa) channels on the membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg) cerebral arteries (100–200 μm) were studied using digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential. Ryanodine (10 μm), an inhibitor of RyR channels, depolarized by 9 mV, increased intracellular [Ca2+] by 46 nm and constricted pressurized (to 60 mmHg) arteries with myogenic tone by 44 μm (∼22 %). Iberiotoxin (100 nm), a blocker of KCa channels, under the same conditions, depolarized the arteries by 10 mV, increased arterial wall calcium by 51 nm, and constricted by 37 μm (∼19 %). The effects of ryanodine and iberiotoxin were not additive and were blocked by inhibitors of voltage-dependent Ca2+ channels. Caffeine (10 mm), an activator of RyR channels, transiently increased arterial wall [Ca2+] by 136 ± 9 nm in control arteries and by 158 ± 12 nm in the presence of iberiotoxin. Caffeine was relatively ineffective in the presence of ryanodine, increasing [calcium] by 18 ± 5 nm. In the presence of blockers of voltage-dependent Ca2+ channels (nimodipine, diltiazem), ryanodine and inhibitors of the SR calcium ATPase (thapsigargin, cyclopiazonic acid) were without effect on arterial wall [Ca2+] and diameter. These results suggest that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca2+ entry through L-type voltage-dependent Ca2+ channels. KCa channels therefore act as a negative feedback control element regulating arterial diameter through a reduction in global intracellular free [Ca2+]. PMID:9490841

Intracellular translocation of calmodulin and Ca{sup 2+}/calmodulin-dependent protein kinase II during the development of hypertrophy in neonatal cardiomyocytes

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

Gangopadhyay, Jaya Pal, E-mail: jaya@bbri.org; Ikemoto, Noriaki; Department of Neurology, Harvard Medical School, Boston, MA 02115

We have recently shown that stimulation of cultured neonatal cardiomyocytes with endothelin-1 (ET-1) first produces conformational disorder within the ryanodine receptor (RyR2) and diastolic Ca{sup 2+} leak from the sarcoplasmic reticulum (SR), then develops hypertrophy (HT) in the cardiomyocytes (Hamada et al., 2009 ). The present paper addresses the following question. By what mechanism does crosstalk between defective operation of RyR2 and activation of the HT gene program occur? Here we show that the immuno-stain of calmodulin (CaM) is localized chiefly in the cytoplasmic area in the control cells; whereas, in the ET-1-treated/hypertrophied cells, major immuno-staining is localized in themore » nuclear region. In addition, fluorescently labeled CaM that has been introduced into the cardiomyocytes using the BioPORTER system moves from the cytoplasm to the nucleus with the development of HT. The immuno-confocal imaging of Ca{sup 2+}/CaM-dependent protein kinase II (CaMKII) also shows cytoplasm-to-nucleus shift of the immuno-staining pattern in the hypertrophied cells. In an early phase of hypertrophic growth, the frequency of spontaneous Ca{sup 2+} transients increases, which accompanies with cytoplasm-to-nucleus translocation of CaM. In a later phase of hypertrophic growth, further increase in the frequency of spontaneous Ca{sup 2+} transients results in the appearance of trains of Ca{sup 2+} spikes, which accompanies with nuclear translocation of CaMKII. The cardio-protective reagent dantrolene (the reagent that corrects the de-stabilized inter-domain interaction within the RyR2 to a normal mode) ameliorates aberrant intracellular Ca{sup 2+} events and prevents nuclear translocation of both CaM and CaMKII, then prevents the development of HT. These results suggest that translocation of CaM and CaMKII from the cytoplasm to the nucleus serves as messengers to transmit the pathogenic signal elicited in the surface membrane and in the RyR2 to the nuclear transcriptional sites to activate HT program.« less

Oscillation spectrum of WASP-33 from the MOST photometry

NASA Astrophysics Data System (ADS)

Mkrtichian, David

2015-08-01

We present results of extended continuous time series photometry of the Delta Scuti type pulsating exoplanet host star WASP-33 obtained in two seasons (2011 and 2013) with the MOST space telescope. Our frequency analysis yealds rich, low-amplitude multi-frequency spectrum of oscillation modes. We discuss possible resonances between the orbiital period of the planet and frequencies of the oscillation modes. We present results of our measurements of planets orbital O-C variations and analyze possible existence of invisible planets in the system. We review recent results of the high-resolution spectroscopic campaign on WASP-33 and confirm the retrograde orbital motion of the planet WASP-33b.

Adventures in transformations: TG, TA, oh my! (Poster abstract)

NASA Astrophysics Data System (ADS)

Ciocca, M.

2015-12-01

(Abstract only) AAVSO made available, through the great volunteer work of Gordon Myers and George Silvis, two very useful tools, Transform Generator and Transform Applier (TG and TA) for transforming instrumental magnitudes to the standard system. I will juxtapose the steps necessary to obtain transformation parameters "the old fashion way" and how can the same result be achieved with these two tools. I will present transformation parameters for the Eastern Kentucky University (EKU) telescope and obtained with the standard field M67. These parameters were applied to photometric results for AE Uma, a short-period, high-amplitude delta Scuti star (Period ~ 0.086 d).

Listening with Only a Third Ear

ERIC Educational Resources Information Center

Barron, Frank

1972-01-01

A review of The Creative Experience" (Grossman), edited by Stanley Rosner and Laurence E. Abt. The Book is essentially a record of conversations with prominent scientists and artists about their life and work. (Author/RY)

Heating the Primordial Soup: X-raying the Circumstellar Disk of RY Lupi

NASA Astrophysics Data System (ADS)

Principe, David

2015-09-01

X-ray irradiation of circumstellar disks plays a vital role in their chemical evolution yet few high resolution X-ray observations exist characterizing both the disk-illuminating radiation field and the soft energy spectrum absorbed by the disk. We propose HETG spectroscopic observations of RY Lupi, a rare example of a nearly edge-on, actively accreting star-disk system within 150 pc. We aim to take advantage of its unique viewing geometry with the goals of (a) determining the intrinsic X-ray spectrum of the central pre-MS star so as to establish whether its X-ray emission can be attributed to accretion shocks or coronal emission, and (b) model the spectrum of X-rays absorbed by its gaseous disk. These results will serve as essential input to models of irradiated, planet-forming disks.

Magnetization and transport properties of single RPd2P2 (R=Y, La-Nd, Sm-Ho, Yb)

NASA Astrophysics Data System (ADS)

Drachuck, Gil; Boehmer, Anna; Bud'Ko, Sergey L.; Canfield, Paul

Single crystals of RPd2P2 (R=Y, La-Nd, Sm-Ho, Yb) were grown using a self-flux method and were characterized by room-temperature powder X-ray diffraction, anisotropic temperature and field dependent magnetization and temperature dependent in-plane resistivity. Anisotropic magnetic properties, arising mostly from crystal electric field (CEF) effects, were observed for most magnetic rare earths. The experimentally estimated CEF parameters B02 were calculated from the anisotropic paramagnetic θab and θcvalues. Ordering temperatures, as well as the polycrystalline averaged paramagnetic Curie-Weiss temperature, θave, were extracted from magnetization and resistivity measurements. Work done at Ames Laboratory was supported by US Department of Energy, Basic Energy Sciences, Division of Materials Sciences and Engineering under Contract No. DE-AC02-07CH111358.

Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

PubMed

Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

2017-10-01

Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol.

PubMed

Cario, Gunnar; Zimmermann, Martin; Romey, Renja; Gesk, Stefan; Vater, Inga; Harbott, Jochen; Schrauder, André; Moericke, Anja; Izraeli, Shai; Akasaka, Takashi; Dyer, Martin J S; Siebert, Reiner; Schrappe, Martin; Stanulla, Martin

2010-07-01

High-level expression of the cytokine receptor-like factor 2 gene, CRLF2, in precursor B-cell acute lymphoblastic leukemia (pB-ALL) was shown to be caused by a translocation involving the IGH@ locus or a deletion juxtaposing CRLF2 with the P2RY8 promoter. To assess its possible prognostic value, CRLF2 expression was analyzed in 555 childhood pB-ALL patients treated according to the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 2000 (ALL-BFM 2000) protocol. Besides CRLF2 rearrangements, high-level CRLF2 expression was seen in cases with supernumerary copies of the CRLF2 locus. On the basis of the detection of CRLF2 rearrangements, a CRLF2 high-expression group (n = 49) was defined. This group had a 6-year relapse incidence of 31% plus or minus 8% compared with 11% plus or minus 1% in the CRLF2 low-expression group (P = .006). This difference was mainly attributable to an extremely high incidence of relapse (71% +/- 19%) in non-high-risk patients with P2RY8-CRLF2 rearrangement. The assessment of CRLF2 aberrations may therefore serve as new stratification tool in Berlin-Frankfurt-Münster-based protocols by identifying additional high-risk patients who may benefit from an intensified and/or targeted treatment.

New insight of hybrid membrane to degrade Congo red and Reactive yellow under sunlight.

PubMed

Rajeswari, A; Jackcina Stobel Christy, E; Pius, Anitha

2018-02-01

A study was carried out to investigate the degradation of organic contaminants (Congo red and Reactive yellow - 105) using cellulose acetate - polystyrene (CA-PS) membrane with and without ZnO impregnation. Scanning electron microscope (SEM), electron dispersive analysis of X-rays (EDAX), Fourier transform infrared spectrometer (FTIR), atomic force microscope (AFM) and thermogravimeric analysis (TG-DTA) analysis were carried out to characterize bare and ZnO impregnated CA-PS membranes. Membrane efficiency was also tested for pure water flux and antifouling performance. The modified membrane showed almost 85% water flux recovery. Blending of ZnO nanoparticles to CA-PS matrix could decrease membrane fouling and increase permeation quality of the membrane with above 90% of photocatalytic degradation efficiency for dyes. The rate of degradation of dyes was observed using UV-Vis spectrometer. Reusability of CA-PS-ZnO membrane was studied and no significant change was noted in the degradation efficiency until fourth cycle. Langmuir-Hinshelwood kinetic model well describes the photo degradation capacity and the degradation of dyes CR and RY - 105 exhibited pseudo-first order kinetics. The regression coefficient (R) of CR and RY - 105 found to be 0.99. The novelty of the prepared CA-PS-ZnO membrane is that it has better efficiency and high thermal stability than our previously reported material. Therefore, ZnO impregnated CA-PS membrane had proved to be an innovative alternative for the degradation of CR and RY - 105 dyes. Copyright © 2017 Elsevier B.V. All rights reserved.

A UV-to-NIR Study of Molecular Gas in the Dust Cavity around RY Lupi

NASA Astrophysics Data System (ADS)

Arulanantham, N.; France, K.; Hoadley, K.; Manara, C. F.; Schneider, P. C.; Alcalá, J. M.; Banzatti, A.; Günther, H. M.; Miotello, A.; van der Marel, N.; van Dishoeck, E. F.; Walsh, C.; Williams, J. P.

2018-03-01

We present a study of molecular gas in the inner disk (r< 20 {au}) around RY Lupi, with spectra from HST-COS, HST-STIS, and VLT-CRIRES. We model the radial distribution of flux from hot gas in a surface layer between r = 0.1–10 au, as traced by Lyα-pumped H2. The result shows H2 emission originating in a ring centered at ∼3 au that declines within r < 0.1 au, which is consistent with the behavior of disks with dust cavities. An analysis of the H2 line shapes shows that a two-component Gaussian profile ({FWHM}}broad,{{{H}}}2}=105 +/- 15 {km} {{{s}}}-1{FWHM}}narrow,{{{H}}}2}=43+/- 13 {km} {{{s}}}-1) is statistically preferred to a single-component Gaussian. We interpret this as tentative evidence for gas emitting from radially separated disk regions (< {r}broad,{{{H}}}2}> ∼ 0.4+/- 0.1 {au};< {r}narrow,{{{H}}}2}> ∼ 3+/- 2 {au}). The 4.7 μm 12CO emission lines are also well fit by two-component profiles (< {r}broad,{CO}}> =0.4+/- 0.1 {au};< {r}narrow,{CO}}> =15+/- 2 {au}). We combine these results with 10 μm observations to form a picture of gapped structure within the mm-imaged dust cavity, providing the first such overview of the inner regions of a young disk. The HST SED of RY Lupi is available online for use in modeling efforts.

Prevention of ventricular arrhythmia and calcium dysregulation in a catecholaminergic polymorphic ventricular tachycardia mouse model carrying calsequestrin-2 mutation.

PubMed

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G; Seidman, Christine E; Berul, Charles I

2011-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, β-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. © 2010 Wiley Periodicals, Inc.

Prevention of Ventricular Arrhythmia and Calcium Dysregulation in a Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model Carrying Calsequestrin-2 Mutation

PubMed Central

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G.; Seidman, Christine E.; Berul, Charles I

2010-01-01

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca2+ overload and increased Ca2+ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results CPVT mouse models that lack CASQ2 were treated with Ca2+-channel inhibitors, β-adrenergic inhibitors, or Mg2+. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca2+ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca2+ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca2+ content in mutant myocytes, diminished diastolic Ca2+ overload, increased systolic Ca2+ amplitude, and prevented Ca2+ oscillations in stressed mutant myocytes. Conclusions Ca2+ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca2+ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca2+ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. PMID:20807279

What is the best reconstruction method after distal gastrectomy for gastric cancer?

PubMed

Lee, Moon-Soo; Ahn, Sang-Hoon; Lee, Ju-Hee; Park, Do Joong; Lee, Hyuk-Joon; Kim, Hyung-Ho; Yang, Han-Kwang; Kim, Nayoung; Lee, Won Woo

2012-06-01

We performed this prospective randomized study to evaluate what is the best reconstruction method after distal gastrectomy for gastric cancer. One hundred fifty-nine patients who underwent laparoscopy-assisted or open gastrectomy for gastric cancer were analyzed from March 2006 to August 2007. Billroth I (B-I) anastomosis, Billroth II (B-II) with Braun anastomosis, and Roux-en-Y (R-Y) anastomosis were applied randomly. Additionally, the patients were divided into two groups based on treatment type: laparoscopic and open operation. Endoscopy and hepatobiliary scans were performed to investigate gastric stasis and enterogastric reflux. The Gastrointestinal Quality of Life Index (GIQLI) was used to evaluate postoperative quality of life, and the hematologic test was used to assess nutritional aspect. Endoscopy revealed that reflux after the R-Y anastomosis procedure was significantly less frequent than after the other anastomosis types at 12 months. Comparison of the GIQLI and the nutritional parameters between the reconstruction types revealed that there were no differences, but a significantly higher GIQLI score was observed in the laparoscopic group immediately following the procedure (P = 0.042). R-Y anastomosis is superior to B-I and B-II with Braun anastomosis in terms of frequency of bile reflux, despite the fact that there is no difference in the postoperative quality-of-life index and nutritional status between reconstructive procedures. The laparoscopic approach is the better option than open surgery in terms of QOL in the immediate postoperative period.

The near-contact binary star RZ Dra revisited

NASA Astrophysics Data System (ADS)

Erdem, A.; Zola, S.; Winiarski, M.

2011-01-01

This paper presents the absolute parameters of RZ Dra. New CCD observations were made at the Mt. Suhora Observatory in 2007. Two photometric data sets (1990 BV and 2007 BVRI) were analysed using modern light-curve synthesis methods. Large asymmetries in the light curves may be explained in terms of a dark starspot on the primary component, an A6 type star. Due to this magnetic activity, the primary component would appear to belong to the class of Ap-stars and would show small amplitude with δ Scuti-type pulsations. With this in mind, a time-series analysis of the residual light curves was made. However, we found no evidence of pulsation behaviour in RZ Dra. Combining the solutions of our light curves and Rucinski et al. (2000)'s radial velocity curves, the following absolute parameters of the components were determined: M1 = 1.63 ± 0.03 M ⊙, M2 = 0.70 ± 0.02 M ⊙, R1 = 1.65 ± 0.02R ⊙, R2 = 1.15 ± 0.02 R ⊙, L1 = 9.72 ± 0.30 L ⊙ and L2 = 0.74 ± 0.10 L ⊙. The distance to RZ Dra was calculated as 400 ± 25 pc, taking into account interstellar extinction. The orbital period of the system was studied using updated O- C information. It was found that the orbital period varied in its long-period sinusoidal form, superimposed on a downward parabola. The parabolic term shows a secular period decrease at a slow rate of 0.06 ± 0.02 s per century and is explained by the mass loss via magnetized wind of the Ap-star primary. The tilted sinusoidal form of the period variation may be considered as an apparent change and may be interpreted in terms of the light-time effect due to the presence of a third body.

On the Couch

ERIC Educational Resources Information Center

Mack, Ed

1972-01-01

Two parts of reading control the pedagogy: statistics and curriculum development. One uses math; the other, the noun. Both live in the twilight of madness." A myth-shattering critique of current practices in the teaching of Reading. (Author/RY)

Greenhouse Gas Reporting Program (GHGRP)

EPA Pesticide Factsheets

Site provides information on EPA's GHG reported data starting with RY 2010 to the present. The site also provides information on regulatory requirements, applicability, how to register a facility and report data, and how to access the GHG data.

Medical climatology in France: the persistence of Neo-Hippocratic ideas in the first half of the twentieth century.

PubMed

Osborne, Michael A; Fogarty, Richard S

2012-01-01

In interwar France the Lyonnais physician Marius Piéry undertook an ambitious Neo-Hippocratic research program to study how atmospheric and terrestrial environments influenced health. Lyon had a number of institutions linked to the colonies and was a center for the training of military physicians. Colonial physicians had a long tradition of contending with the diseases of tropical environments, and their ideas and many returned colonials circulated in Lyon and its region. Piéry was a physician during World War I and published on military medical topics. He also included colonial and military health concerns in his more mature works from the 1930s. An advocate of the close study of the physical sciences, he investigated the radioactive gases of health spas and the effects of altitude on pulmonary tuberculosis, and he directed a meteorological observatory.

Effect of proximal vagotomy and Roux-en-Y diversion on gastric emptying kinetics in asymptomatic patients.

PubMed

Urbain, J L; Penninckx, F; Siegel, J A; Vandenborre, P; Van Cutsem, E; Vandenmaegdenbergh, V; De Roo, M

1990-10-01

The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro-jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In-111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R-Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying.

Seasonal induction of alternative principal pathway for rose flower scent

PubMed Central

Hirata, Hiroshi; Ohnishi, Toshiyuki; Tomida, Kensuke; Ishida, Haruka; Kanda, Momoyo; Sakai, Miwa; Yoshimura, Jin; Suzuki, Hideyuki; Ishikawa, Takamasa; Dohra, Hideo; Watanabe, Naoharu

2016-01-01

Ecological adaptations to seasonal changes are often observed in the phenotypic traits of plants and animals, and these adaptations are usually expressed through the production of different biochemical end products. In this study, ecological adaptations are observed in a biochemical pathway without alteration of the end products. We present an alternative principal pathway to the characteristic floral scent compound 2-phenylethanol (2PE) in roses. The new pathway is seasonally induced in summer as a heat adaptation that uses rose phenylpyruvate decarboxylase (RyPPDC) as a novel enzyme. RyPPDC transcript levels and the resulting production of 2PE are increased time-dependently under high temperatures. The novel summer pathway produces levels of 2PE that are several orders of magnitude higher than those produced by the previously known pathway. Our results indicate that the alternative principal pathway identified here is a seasonal adaptation for managing the weakened volatility of summer roses. PMID:26831950

An ultraviolet and visible spectroscopic study of a pulsational cycle of RY Sagittarii

NASA Technical Reports Server (NTRS)

Clayton, Geoffrey C.; Lawson, W. A.; Cottrell, P. L.; Whitney, Barbara A.; Stanford, S. Adam; De Ruyter, Frank

1994-01-01

High-dispersion visible and ultraviolet spectra and UBVRI photometry, covering a complete pulsation of the R Coronae Borealis star RY Sgr, have been obtained. The UV spectra were the first high-dispersion data ever obtained for the star. Together these observations comprise the most complete data set covering an RCB star pulsation cycle. The cycle observed was somewhat anomalous as it was affected by a second 55 day pulsation period as well as the primary 38 day period. However, the visible spectra showed the typical line splitting and radial velocity variations which have been observed previously. The simultaneous UV spectra showed much smaller, and phase-shifted, velocity variations than those seen in the visible. No evidence was seen of shock-induced emission at Mg II. These observations provide some support for the models of pulsating hydrogen deficient stars developed by Saio & Wheeler.

Temperature sensitivity of ligand-gated ion channels: ryanodine receptor case

NASA Astrophysics Data System (ADS)

Iaparov, B. I.; Moskvin, A. S.; Solovyova, O. E.

2017-11-01

Temperature influences all biochemical processes, in particular, excitation-contraction coupling(ECC) in cardiac cells. In this work we propose a theoretical explanation of temperature effects on an isolated ryanodine receptor calcium release channel (RyR channel) within the electron-conformational (EC) model. We show that the EC model with an Arrhenius-like temperature dependence of the “internal” and “external” frictions and a specific thermosensitivity of the tunnelling “open ↔ closed” transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyR channels. Interestingly that a small change of the activation energy for the “internal” friction can make an ion channel either heat-inhibited or heat-activated while the “external” friction doesn’t play a key role in temperature sensitivity: neglect of “external” friction doesn’t change the channel’s temperature sensitivity qualitatively.

Spectra disentangling applied to the Hyades binary θ2 Tauri AB: new orbit, orbital parallax and component properties

NASA Astrophysics Data System (ADS)

Torres, K. B. V.; Lampens, P.; Frémat, Y.; Hensberge, H.; Lebreton, Y.; Škoda, P.

2011-01-01

Aims: θ^2 Tau is a detached and single-lined interferometric-spectroscopic binary as well as the most massive binary system of the Hyades cluster. The system revolves in an eccentric orbit with a periodicity of 140.7 days. Its light curve furthermore shows a complex pattern of δ Scuti-type pulsations. The secondary has a similar temperature but is less evolved and fainter than the primary. In addition, it is rotating more rapidly. Since the composite spectra are heavily blended, the direct extraction of radial velocities over the orbit of component B was hitherto unsuccessful. Our aim is to reveal the spectrum of the fainter component and its corresponding Doppler shifts in order to improve the accuracy of the physical properties of this important “calibrator” system. Methods: Using high-resolution spectroscopic data recently obtained with the Elodie (Observatoire de Haute-Provence, France) and Hermes (Roque de Los Muchachos, La Palma, Spain) spectrographs, and applying a spectra disentangling algorithm to three independent data sets including CfA spectra (Oak Ridge Observatory, USA), we derived an improved spectroscopic orbit. We next used a code based on simulated annealing and general least-squares minimization to refine the orbital solution by performing a combined astrometric-spectroscopic analysis based on the new spectroscopy and the long-baseline data from the Mark III optical interferometer. Results: As a result of the performed disentangling, and notwithstanding the high degree of blending, the velocity amplitude of the fainter component is obtained in a direct and objective way. Major progress based on this new determination includes an improved computation of the orbital parallax (still consistent with previous values). Our mass ratio is in good agreement with the older estimates of Peterson et al. (1991, 1993), but the mass of the primary is 15-25% higher than the more recent estimates by Torres et al. (1997) and Armstrong et al. (2006). Conclusions: The evolutionary status of both components is re-evaluated in the light of the revisited properties of θ^2 Tau AB. Due to the strategic position of the components in the turnoff region of the cluster, the new determinations imply stricter constraints for the age and the metallicity of the Hyades cluster. We conclude that the location of component B can be explained by current evolutionary models, but the location (and the status) of the more evolved component A is not trivially explained and requires a detailed abundance analysis of its disentangled spectrum. The improved accuracy (at the 2% level) on the stellar masses provides a useful basis for the comparison of the observed pulsation frequencies with suitable theoretical models. Based on observations obtained at the 1.93-m telescope of the Observatoire de Haute Provence, the 1.2-m Mercator telescope at the Roque de los Muchachos Observatory (in the framework of the Hermes Consortium) and the 1.5-m Wyeth telescope at Oak Ridge Observatory.Full Table 4 is only available in electronic form at http://www.aanda.org

Hydrogen sulfide: a novel gaseous signaling molecule and intracellular Ca2+ regulator in rat parotid acinar cells.

PubMed

Moustafa, Amira; Habara, Yoshiaki

2015-10-01

In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist upregulated endothelial NO synthase in parotid tissue. NO and H2S donors increased the intracellular Ca(2+) concentration ([Ca(2+)]i). This was not affected by inhibitors of phospholipase C and inositol 1,4,5-trisphosphate receptors, but was decreased by blockers of ryanodine receptors (RyRs), soluble guanylyl cyclase, and protein kinase G. The H2S donor evoked NO production, which was decreased by blockade of NO synthases or phosphoinositide 3-kinase or by hypotaurine, an H2S scavenger. The H2S donor-induced [Ca(2+)]i increase was diminished by a NO scavenger or the NO synthases blocker. These results suggest that NO and H2S play important roles in regulating [Ca(2+)]i via soluble guanylyl cyclase-cGMP-protein kinase G-RyRs, but not via inositol 1,4,5-trisphosphate receptors. The effect of H2S may be partially through NO produced via phosphoinositide 3-kinase-Akt-endothelial NO synthase. It was concluded that both gases regulate [Ca(2+)]i in a synergistic way, mainly via RyRs in rat parotid acinar cells. Copyright © 2015 the American Physiological Society.

Suppression of Arrhythmia by Enhancing Mitochondrial Ca2+ Uptake in Catecholaminergic Ventricular Tachycardia Models.

PubMed

Schweitzer, Maria K; Wilting, Fabiola; Sedej, Simon; Dreizehnter, Lisa; Dupper, Nathan J; Tian, Qinghai; Moretti, Alessandra; My, Ilaria; Kwon, Ohyun; Priori, Silvia G; Laugwitz, Karl-Ludwig; Storch, Ursula; Lipp, Peter; Breit, Andreas; Mederos Y Schnitzler, Michael; Gudermann, Thomas; Schredelseker, Johann

2017-12-01

Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca 2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca 2+ handling. Therefore, intracellular Ca 2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca 2+ transport proteins are important regulators of cardiac Ca 2+ handling. Here we evaluated the potential of pharmacological activation of mitochondrial Ca 2+ uptake for the treatment of cardiac arrhythmia. To this aim,we tested substances that enhance mitochondrial Ca 2+ uptake for their ability to suppress arrhythmia in a murine model for ryanodine receptor 2 (RyR2)-mediated catecholaminergic polymorphic ventricular tachycardia (CPVT) in vitro and in vivo and in induced pluripotent stem cell-derived cardiomyocytes from a CPVT patient. In freshly isolated cardiomyocytes of RyR2 R4496C/WT mice efsevin, a synthetic agonist of the voltage-dependent anion channel 2 (VDAC2) in the outer mitochondrial membrane, prevented the formation of diastolic Ca 2+ waves and spontaneous action potentials. The antiarrhythmic effect of efsevin was abolished by blockade of the mitochondrial Ca 2+ uniporter (MCU), but could be reproduced using the natural MCU activator kaempferol. Both mitochondrial Ca 2+ uptake enhancers (MiCUps), efsevin and kaempferol, significantly reduced episodes of stress-induced ventricular tachycardia in RyR2 R4496C/WT mice in vivo and abolished diastolic, arrhythmogenic Ca 2+ events in human iPSC-derived cardiomyocytes.

Monitoring DNA triplex formation using multicolor fluorescence and application to insulin-like growth factor I promoter downregulation.

PubMed

Hégarat, Nadia; Novopashina, Darya; Fokina, Alesya A; Boutorine, Alexandre S; Venyaminova, Alya G; Praseuth, Danièle; François, Jean-Christophe

2014-03-01

Inhibition of insulin-like growth factor I (IGF-I) signaling is a promising antitumor strategy and nucleic acid-based approaches have been investigated to target genes in the pathway. Here, we sought to modulate IGF-I transcriptional activity using triple helix formation. The IGF-I P1 promoter contains a purine/pyrimidine (R/Y) sequence that is pivotal for transcription as determined by deletion analysis and can be targeted with a triplex-forming oligonucleotide (TFO). We designed modified purine- and pyrimidine-rich TFOs to bind to the R/Y sequence. To monitor TFO binding, we developed a fluorescence-based gel-retardation assay that allowed independent detection of each strand in three-stranded complexes using end-labeling with Alexa 488, cyanine (Cy)3 and Cy5 fluorochromes. We characterized TFOs for their ability to inhibit restriction enzyme activity, compete with DNA-binding proteins and inhibit IGF-I transcription in reporter assays. TFOs containing modified nucleobases, 5-methyl-2'-deoxycytidine and 5-propynyl-2'-deoxyuridine, specifically inhibited restriction enzyme cleavage and formed triplexes on the P1 promoter fragment. In cells, deletion of the R/Y-rich sequence led to 48% transcriptional inhibition of a reporter gene. Transfection with TFOs inhibited reporter gene activity to a similar extent, whereas transcription from a mutant construct with an interrupted R/Y region was unaffected, strongly suggesting the involvement of triplex formation in the inhibitory mechanisms. Our results indicate that nuclease-resistant TFOs will likely inhibit endogenous IGF-I gene function in cells. © 2014 FEBS.

Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology.

PubMed

Tilan, Jason; Kitlinska, Joanna

2016-02-01

Neuropeptide Y (NPY) is a sympathetic neurotransmitter with pleiotropic actions, many of which are highly relevant to tumor biology. Consequently, the peptide has been implicated as a factor regulating the growth of a variety of tumors. Among them, two pediatric malignancies with high endogenous NPY synthesis and release - neuroblastoma and Ewing sarcoma - became excellent models to investigate the role of NPY in tumor growth and progression. The stimulatory effect on tumor cell proliferation, survival, and migration, as well as angiogenesis in these tumors, is mediated by two NPY receptors, Y2R and Y5R, which are expressed in either a constitutive or inducible manner. Of particular importance are interactions of the NPY system with the tumor microenvironment, as hypoxic conditions commonly occurring in solid tumors strongly activate the NPY/Y2R/Y5R axis. This activation is triggered by hypoxia-induced up-regulation of Y2R/Y5R expression and stimulation of dipeptidyl peptidase IV (DPPIV), which converts NPY to a selective Y2R/Y5R agonist, NPY(3-36). While previous studies focused mainly on the effects of NPY on tumor growth and vascularization, they also provided insight into the potential role of the peptide in tumor progression into a metastatic and chemoresistant phenotype. This review summarizes our current knowledge of the role of NPY in neuroblastoma and Ewing sarcoma and its interactions with the tumor microenvironment in the context of findings in other malignancies, as well as discusses future directions and potential clinical implications of these discoveries. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Hick'ry Stick: It's Time to Change the Tune.

ERIC Educational Resources Information Center

Cryan, John R.; Smith, Jamie C.

1981-01-01

Evidence indicates that violence in our classrooms only breeds more violence in and out of the school. Corporal punishment is worse than useless as a deterrent to misbehavior: it must be considered actively harmful. (Author/IRT)

Burst discharges in neurons of the thalamic reticular nucleus are shaped by calcium-induced calcium release.

PubMed

Coulon, Philippe; Herr, David; Kanyshkova, Tatyana; Meuth, Patrick; Budde, Thomas; Pape, Hans-Christian

2009-01-01

The nucleus reticularis thalami (NRT) is a layer of inhibitory neurons that surrounds the dorsal thalamus. It appears to be the 'pacemaker' of certain forms of slow oscillations in the thalamus and was proposed to be a key determinant of the internal attentional searchlight as well as the origin of hypersynchronous activity during absence seizures. Neurons of the NRT exhibit a transient depolarization termed low threshold spike (LTS) following sustained hyperpolarization. This is caused by the activation of low-voltage-activated Ca2+ channels (LVACC). Although the role of these channels in thalamocortical oscillations was studied in great detail, little is known about the downstream intracellular Ca2+ signalling pathways and their feedback onto the oscillations. A signalling triad consisting of the sarco(endo)plasmic reticulum calcium ATPase (SERCA), Ca2+ activated K+ channels (SK2), and LVACC is active in dendrites of NRT neurons and shapes rhythmic oscillations. The aim of our study was to find out (i) if and how Ca2+-induced Ca2+ release (CICR) via ryanodine receptors (RyR) can be evoked in NRT neurons and (ii) how the released Ca2+ affects burst activity. Combining electrophysiological, immunohistochemical, and two-photon Ca2+ imaging techniques, we show that CICR in NRT neurons takes place by a cell-type specific coupling of LVACC and RyR. CICR could be evoked by the application of caffeine, by activation of LVACC, or by repetitive LTS generation. During the latter, CICR contributed 30% to the resulting build-up of [Ca2+]i. CICR was abolished by cyclopiazonic acid, a specific blocker for SERCA, or by high concentrations of ryanodine (50 microM). Unlike other thalamic nuclei, in the NRT the activation of high-voltage-activated Ca2+ channels failed to evoke CICR. While action potentials contributed little to the build-up of [Ca2+]i upon repetitive LTS generation, the Ca2+ released via RyR significantly reduced the number of action potentials during an LTS and reduced the neurons' low threshold activity, thus potentially reducing hypersynchronicity. This effect persisted in the presence of the SK2 channel blocker apamin. We conclude that the activation of LVACC specifically causes CICR via RyR in neurons of the NRT, thereby adding a Ca2+-dependent intracellular route to the mechanisms determining rhythmic oscillatory bursting in this nucleus.

LASR-Guided Variability Subtraction: The Linear Algorithm for Significance Reduction of Stellar Seismic Activity

NASA Astrophysics Data System (ADS)

Horvath, Sarah; Myers, Sam; Ahlers, Johnathon; Barnes, Jason W.

2017-10-01

Stellar seismic activity produces variations in brightness that introduce oscillations into transit light curves, which can create challenges for traditional fitting models. These oscillations disrupt baseline stellar flux values and potentially mask transits. We develop a model that removes these oscillations from transit light curves by minimizing the significance of each oscillation in frequency space. By removing stellar variability, we prepare each light curve for traditional fitting techniques. We apply our model to $\\delta$-Scuti KOI-976 and demonstrate that our variability subtraction routine successfully allows for measuring bulk system characteristics using traditional light curve fitting. These results open a new window for characterizing bulk system parameters of planets orbiting seismically active stars.

Calcium-calmodulin-dependent protein kinase mediates the intracellular signalling pathways of cardiac apoptosis in mice with impaired glucose tolerance.

PubMed

Federico, Marilen; Portiansky, Enrique L; Sommese, Leandro; Alvarado, Francisco J; Blanco, Paula G; Zanuzzi, Carolina N; Dedman, John; Kaetzel, Marcia; Wehrens, Xander H T; Mattiazzi, Alicia; Palomeque, Julieta

2017-06-15

Spontaneous sarcoplasmic reticulum (SR) Ca 2+ release events increased in fructose-rich diet mouse (FRD) myocytes vs. control diet (CD) mice, in the absence of significant changes in SR Ca 2+ load. In HEK293 cells, hyperglycaemia significantly enhanced [ 3 H]ryanodine binding and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2-S2814 residue vs. normoglycaemia. These increases were prevented by CaMKII inhibition. FRD significantly augmented cardiac apoptosis in WT vs. CD-WT mice, which was prevented by co-treatment with the reactive oxygen species scavenger Tempol. Oxidative stress was also increased in FRD-SR-autocamide inhibitory peptide (AIP) mice, expressing the SR-targeted CaMKII inhibitor AIP, without any significant enhancement of apoptosis vs. CD-SR-AIP mice. FRD produced mitochondrial swelling and membrane depolarization in FRD-WT mice but not in FRD-S2814A mice, in which the CaMKII site on ryanodine receptor 2 was ablated. FRD decreased mitochondrial area, mean Feret diameter and the mean distance between SR and the outer mitochondrial membrane vs. CD hearts. This remodelling was prevented in AC3I mice, with cardiac-targeted CaMKII inhibition. The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We show that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca 2+ /calmodulin-protein kinase (CaMKII) activity, ryanodine receptor 2 (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca 2+ leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. We generated a pre-diabetic model in FRD mice. FRD mice showed an increase in oxidative stress, hypertrophy and systolic dysfunction. FRD myocytes exhibited enhanced SR Ca 2+ spontaneous events in the absence of SR Ca 2+ load alterations vs. control-diet (CD) myocytes. In HEK293 cells, hyperglycaemia significantly enhanced [ 3 H]ryanodine binding and CaMKII phosphorylation of RyR2-S2814 residue vs. normoglycaemia. CaMKII inhibition prevented hyperglycaemia-induced alterations. FRD also evoked cardiac apoptosis in WT mice vs. CD-WT mice. Co-treatment with the reactive oxygen species scavenger Tempol prevented FRD-induced apoptosis in WT mice. In contrast, FRD enhanced oxidative stress but not apoptosis in FRD-SR-AIP mice, in which a CaMKII inhibitor is targeted to the SR. FRD produced mitochondrial membrane depolarization in WT mice but not in S2814A mice, in which the CaMKII phosphorylation site on RyR2 was ablated. Furthermore, FRD decreased mitochondrial area, mean Feret diameter and mean SR-mitochondrial distance vs. CD-WT hearts. This remodelling was prevented in AC3I mice, with cardiac-targeted CaMKII inhibition. CaMKII phosphorylation of RyR2, SR Ca 2+ leak and mitochondrial membrane depolarization are critically involved in the apoptotic pathway of the pre-diabetic heart. The FRD-induced decrease in SR-mitochondrial distance is likely to additionally favour Ca 2+ transit between the two organelles. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Nitrogen Trifluoride: Its Chemistry, Toxicity, and Safe Handling.

DTIC Science & Technology

1976-11-12

Hopkins University . LPAI—LtIP-1 , Nov 1961 . 27. Stauffer Chemical Co. Technical Bulletin. “Nitrogen Trifluoride and Tetrafluorohydrazine ” . Market ...Continued ) United Technologies Corp. Naval Postgraduate School Pratt & Whitney Aircraft Div. Attn: Libra ry, Tech. Repts. Florida Researc h & Development Ctr

Federal Reserve Glos'sa-ry.

ERIC Educational Resources Information Center

Board of Governors of the Federal Reserve System, Washington, DC.

Designed for the general public and possibly suitable also for high school economics students, this booklet briefly explains the terminology associated with general economic concepts about banking and the Federal Reserve System. Part 1 deals with financial regulators and institutions, including nondeposit intermediaries and depository…

Francesco's last divertissement: The Little Prince's Universe

NASA Astrophysics Data System (ADS)

Tozzi, P.

The last accomplishment of Francesco in public outreach, was a book devoted to children, based on the character of the Little Prince by Antoine de Saint-Exupéry. Francesco completed the text, and Sylvie made the drawings. The book is now finally printed.

Modelling high arctic percent vegetation cover using field digital images and high resolution satellite data

NASA Astrophysics Data System (ADS)

Liu, Nanfeng; Treitz, Paul

2016-10-01

In this study, digital images collected at a study site in the Canadian High Arctic were processed and classified to examine the spatial-temporal patterns of percent vegetation cover (PVC). To obtain the PVC of different plant functional groups (i.e., forbs, graminoids/sedges and mosses), field near infrared-green-blue (NGB) digital images were classified using an object-based image analysis (OBIA) approach. The PVC analyses comparing different vegetation types confirmed: (i) the polar semi-desert exhibited the lowest PVC with a large proportion of bare soil/rock cover; (ii) the mesic tundra cover consisted of approximately 60% mosses; and (iii) the wet sedge consisted almost exclusively of graminoids and sedges. As expected, the PVC and green normalized difference vegetation index (GNDVI; (RNIR - RGreen)/(RNIR + RGreen)), derived from field NGB digital images, increased during the summer growing season for each vegetation type: i.e., ∼5% (0.01) for polar semi-desert; ∼10% (0.04) for mesic tundra; and ∼12% (0.03) for wet sedge respectively. PVC derived from field images was found to be strongly correlated with WorldView-2 derived normalized difference spectral indices (NDSI; (Rx - Ry)/(Rx + Ry)), where Rx is the reflectance of the red edge (724.1 nm) or near infrared (832.9 nm and 949.3 nm) bands; Ry is the reflectance of the yellow (607.7 nm) or red (658.8 nm) bands with R2's ranging from 0.74 to 0.81. NDSIs that incorporated the yellow band (607.7 nm) performed slightly better than the NDSIs without, indicating that this band may be more useful for investigating Arctic vegetation that often includes large proportions of senescent vegetation throughout the growing season.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Facilitation of cytosolic calcium wave propagation by local calcium uptake into the sarcoplasmic reticulum in cardiac myocytes.

PubMed

Maxwell, Joshua T; Blatter, Lothar A

2012-12-01

The widely accepted paradigm for cytosolic Ca(2+) wave propagation postulates a 'fire-diffuse-fire' mechanism where local Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca(2+) release channels diffuses towards and activates neighbouring release sites, resulting in a propagating Ca(2+) wave. A recent challenge to this paradigm proposed the requirement for an intra-SR 'sensitization' Ca(2+) wave that precedes the cytosolic Ca(2+) wave and primes RyRs from the luminal side to CICR. Here, we tested this hypothesis experimentally with direct simultaneous measurements of cytosolic ([Ca(2+)](i); rhod-2) and intra-SR ([Ca(2+)](SR); fluo-5N) calcium signals during wave propagation in rabbit ventricular myocytes, using high resolution fluorescence confocal imaging. The increase in [Ca(2+)](i) at the wave front preceded depletion of the SR at each point along the calcium wave front, while during this latency period a transient increase of [Ca(2+)](SR) was observed. This transient elevation of [Ca(2+)](SR) could be identified at individual release junctions and depended on the activity of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA). Increased SERCA activity (β-adrenergic stimulation with 1 μM isoproterenol (isoprenaline)) decreased the latency period and increased the amplitude of the transient elevation of [Ca(2+)](SR), whereas inhibition of SERCA (3 μM cyclopiazonic acid) had the opposite effect. In conclusion, the data provide experimental evidence that local Ca(2+) uptake by SERCA into the SR facilitates the propagation of cytosolic Ca(2+) waves via luminal sensitization of the RyR, and supports a novel paradigm of a 'fire-diffuse-uptake-fire' mechanism for Ca(2+) wave propagation in cardiac myocytes.

Atomic Data and Spectral Line Intensities for Ni XI

NASA Technical Reports Server (NTRS)

Bhatia, A. K.; Landi, E.

2010-01-01

Electron impact collision strengths, energy levels, oscillator strengths and spontaneous radiative decay rates are calculated for Ni XI. We include in the calculations the 10 lowest configurations, corresponding to 164 fine structure levels: 3s(sup 2)3p(sup 6), 3s(sup 2)3p(sup 5)3d, 3s(sup 2)3p(sup 4)3d(sup 2), 3s3p(sup 6)3d, 3s(sup 2)3p(sup 5)4l and 3s3p6 4l with l =.s, p, d. Collision strengths are calculated at five incident energies for all transitions: 7.1, 16.8, 30.2, 48.7 and 74.1 Ry above the threshold of each transition. An additional energy, very close to the transition threshold, has been added, whose value is between 0.06 Ry and 0.25 Ry depending on the lower level. Calculations have been carried out using the Flexible Atomic Code and the distorted wave approximation. Excitation rate coefficients are calculated as a function of electron temperature by assuming a Maxwellian electron velocity distribution. Using the excitation rate coefficients and the radiative transition rates of the present work, combined with Close Coupling collision excitation rate coefficient available in the literature for the lowest 17 levels, statistical equilibrium equations for level populations are solved at electron densities covering the 10(exp 8)-10(exp 14) cu cm range and at an electron temperature of logT(sub c)(K)=6.1, corresponding to the maximum abundance of Ni XI. Spectral line intensities are calculated, and their diagnostic relevance is discussed. This dataset will be made available in the next version of the CHIANTI database.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging.

PubMed

Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian

2014-10-06

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

PubMed Central

Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

2014-01-01

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. PMID:25100314

The Effects of Industrial Protective Gloves and Hand Skin Temperatures on Hand Grip Strength and Discomfort Rating

PubMed Central

2017-01-01

Daily working activities and functions require a high contribution of hand and forearm muscles in executing grip force. To study the effects of wearing different gloves on grip strength, under a variety of hand skin temperatures, an assessment of the maximum grip strength was performed with 32 healthy male workers with a mean age (standard deviation) of 30.44 (5.35) years wearing five industrial gloves at three hand skin temperatures. Their ages and anthropometric characteristics including body mass index (BMI), hand length, hand width, hand depth, hand palm, and wrist circumference were measured. The hand was exposed to different bath temperatures (5 °C, 25 °C, and 45 °C) and hand grip strength was measured using a Jamar hydraulic hand dynamometer with and without wearing the gloves (chemical protection glove, rubber insulating glove, anti-vibration impact glove, cotton yarn knitted glove, and RY-WG002 working glove). The data were analyzed using the Shapiro–Wilk test, Pearson correlation coefficient, Tukey test, and analysis of variance (ANOVA) of the within-subject design analysis. The results showed that wearing gloves significantly affected the maximum grip strength. Wearing the RY-WG002 working glove produced a greater reduction on the maximum grip when compared with the bare hand, while low temperatures (5 °C) had a significant influence on grip when compared to medium (25 °C) and high (45 °C) hand skin temperatures. In addition, participants felt more discomfort in both environmental extreme conditions. Furthermore, they reported more discomfort while wearing neoprene, rubber, and RY-WG002 working gloves. PMID:29207573

Properties of Ca2+ release induced by clofibric acid from the sarcoplasmic reticulum of mouse skeletal muscle fibres

PubMed Central

Ikemoto, Takaaki; Endo, Makoto

2001-01-01

To characterize the effect of clofibric acid (Clof) on the Ca2+ release mechanism in the sarcoplasmic reticulum (SR) of skeletal muscle, we analysed the properties of Clof-induced Ca2+ release under various conditions using chemically skinned skeletal muscle fibres of the mouse.Clof (>0.5 mM) released Ca2+ from the SR under Ca2+-free conditions buffered with 10 mM EGTA (pCa >8).Co-application of ryanodine and Clof at pCa >8 but not ryanodine alone reduced the Ca2+ uptake capacity of the SR. Thus, Ca2+ release induced by Clof at pCa >8 must be a result of the activation of the ryanodine receptor (RyR).At pCa >8, (i) Clof-induced Ca2+ release was inhibited by adenosine monophosphate (AMP), (ii) the inhibitory effect of Mg2+ on the Clof-induced Ca2+ release was saturated at about 1 mM, and (iii) Clof-induced Ca2+ release was not inhibited by procaine (10 mM). These results indicate that Clof may activate the RyR-Ca2+ release channels in a manner different from Ca2+-induced Ca2+ release (CICR).In addition to this unique mode of opening, Clof also enhanced the CICR mode of opening of RyR-Ca2+ release channels.Apart from CICR, a high concentration of Ca2+ might also enhance the unique mode of opening by Clof.These results suggest that some features of Ca2+ release activated by Clof are similar to those of physiological Ca2+ release (PCR) in living muscle cells and raise the possibility that Clof may be useful in elucidating the mechanism of PCR in skeletal muscle. PMID:11606311

GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity

PubMed Central

Moon, Younghye; Cao, Yenong; Zhu, Jingjing; Xu, Yuanyuan; Balkan, Wayne; Buys, Emmanuel S.; Diaz, Francisca; Kerrick, W. Glenn; Hare, Joshua M.

2017-01-01

Abstract Aim: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. Results: GSNOR null (GSNOR−/−) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR−/− lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR−/− TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR−/− TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR−/− muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. Innovation: GSNOR may act as a “brake” on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. Conclusions: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165–181. PMID:27412893

In Vitro Biologic Activities of the Antimicrobials Triclocarban, Its Analogs, and Triclosan in Bioassay Screens: Receptor-Based Bioassay Screens

PubMed Central

Ahn, Ki Chang; Zhao, Bin; Chen, Jiangang; Cherednichenko, Gennady; Sanmarti, Enio; Denison, Michael S.; Lasley, Bill; Pessah, Isaac N.; Kültz, Dietmar; Chang, Daniel P.Y.; Gee, Shirley J.; Hammock, Bruce D.

2008-01-01

Background Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. Objectives In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays. Materials and methods We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1). Results Some carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect. Conclusions Carbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS. PMID:18795164

Iron Mediates N-Methyl-d-aspartate Receptor-dependent Stimulation of Calcium-induced Pathways and Hippocampal Synaptic Plasticity*

PubMed Central

Muñoz, Pablo; Humeres, Alexis; Elgueta, Claudio; Kirkwood, Alfredo; Hidalgo, Cecilia; Núñez, Marco T.

2011-01-01

Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-d-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP. PMID:21296883

Evaluation of Lactic Acid Bacteria Isolated from Fermented Plant Products for Antagonistic Activity Against Urinary Tract Pathogen Staphylococcus saprophyticus.

PubMed

Tsai, Cheng-Chih; Lai, Tzu-Min; Lin, Pei-Pei; Hsieh, You-Miin

2018-06-01

Urinary tract infections (UTIs) are the most common infectious diseases in infants and the elderly; they are also the most common among nosocomial infections. The treatment of UTIs usually involves a short-term course of antibiotics. The purpose of this study was to identify the strains of lactic acid bacteria (LAB) that can inhibit the urinary tract pathogen Staphylococcus saprophyticus, as alternatives to antibiotics. In this study, we collected 370 LAB strains from fermented plant products and reference strains from the Bioresources Collection and Research Center (BCRC). Using spent culture supernatants (SCS), we then screened these LAB strains with for antimicrobial effects on urinary tract pathogens by the well-diffusion assay. Seven LAB strains-PM2, PM68, PM78, PM201, PM206, PM229, and RY2-exhibited inhibitory activity and were evaluated for anti-growth activity against urinary tract pathogens by the co-culture inhibition assay. Anti-adhesion and anti-invasion activities against urinary tract pathogens were evaluated using the SV-HUC-1 urothelial cell cultures. The results revealed that the survival rate of S. saprophyticus ranged from 0.9-2.96%, with the pH continuously decreasing after co-culture with LAB strains for 4 h. In the competitive adhesion assay, the exclusion and competition groups performed better than the displacement group. In the SV-HUC-1 cell invasion assay, PM201, PM206, PM229, and RY2 were found to inhibit the invasion of SV-HUC-1 cells by S. saprophyticus BCRC 10786. To conclude, RY2, PM229, and PM68 strains exhibited inhibitory activity against the urinary tract pathogen S. saprophyticus.

Telomeric P elements associated with cytotype regulation of the P transposon family in Drosophila melanogaster.

PubMed Central

Stuart, Jeremy R; Haley, Kevin J; Swedzinski, Douglas; Lockner, Samuel; Kocian, Paul E; Merriman, Peter J; Simmons, Michael J

2002-01-01

P elements inserted at the left end of the Drosophila X chromosome were isolated genetically from wild-type P strains. Stocks carrying these elements were tested for repression of P-strain-induced gonadal dysgenesis in females and for repression of transposase-catalyzed P-element excision in males and females. Both traits were repressed by stocks carrying either complete or incomplete P elements inserted near the telomere of the X chromosome in cytological region 1A, but not by stocks carrying only nontelomeric X-linked P elements. All three of the telomeric P elements that were analyzed at the molecular level were inserted in one of the 1.8-kb telomere-associated sequence (TAS) repeats near the end of the X chromosome. Stocks with these telomeric P elements strongly repressed P-element excision induced in the male germline by a P strain or by the transposase-producing transgenes H(hsp/CP)2, H(hsp/CP)3, a combination of these two transgenes, and P(ry(+), delta2-3)99B. For H(hsp/CP)2 and P(ry(+), delta2-3)99B, the repression was also effective when the flies were subjected to heat-shock treatments. However, these stocks did not repress the somatic transposase activity of P(ry(+), delta2-3)99B. Repression of transposase activity in the germline required maternal transmission of the telomeric P elements themselves. Paternal transmission of these elements, or maternal transmission of the cytoplasm from carriers, both were insufficient to repress transposase activity. Collectively, these findings indicate that the regulatory abilities of telomeric P elements are similar to those of the P cytotype. PMID:12524339

Evaluation of the mature grain phytase candidate HvPAPhy_a gene in barley (Hordeum vulgare L.) using CRISPR/Cas9 and TALENs.

PubMed

Holme, Inger B; Wendt, Toni; Gil-Humanes, Javier; Deleuran, Lise C; Starker, Colby G; Voytas, Daniel F; Brinch-Pedersen, Henrik

2017-09-01

In the present study, we utilized TALEN- and CRISPR/Cas9-induced mutations to analyze the promoter of the barley phytase gene HvPAPhy_a. The purpose of the study was dual, validation of the PAPhy_a enzyme as the main contributor of the mature grain phytase activity (MGPA), as well as validating the importance of a specific promoter region of the PAPhy_a gene which contains three overlapping cis-acting regulatory elements (GCN4, Skn1 and the RY-element) known to be involved in gene expression during grain filling. The results confirm that the barley PAPhy_a enzyme is the main contributor to the MGPA as grains of knock-out lines show very low MGPA. Additionally, the analysis of the HvPAPhy_a promoter region containing the GCN4/Skn1/RY motif highlights its importance for HvPAPhy_a expression as the MGPA in grains of plant lines with mutations within this motif is significantly reduced. Interestingly, lines with deletions located downstream of the motif show even lower MGPA levels, indicating that the GCN4/SKn1/RY motif is not the only element responsible for the level of PAPhy_a expression during grain maturation. Mutant grains with very low MPGA showed delayed germination as compared to grains of wild type barley. As grains with high levels of preformed phytases would provide more readily available phosphorous needed for a fast germination, this indicates that faster germination may be implicated in the positive selection of the ancient PAPhy gene duplication that lead to the creation of the PAPhy_a gene.

Perturbation theory for fractional Brownian motion in presence of absorbing boundaries.

PubMed

Wiese, Kay Jörg; Majumdar, Satya N; Rosso, Alberto

2011-06-01

Fractional Brownian motion is a Gaussian process x(t) with zero mean and two-time correlations (x(t(1))x(t(2)))=D(t(1)(2H)+t(2)(2H)-|t(1)-t(2)|(2H)), where H, with 0

Facilitation of cytosolic calcium wave propagation by local calcium uptake into the sarcoplasmic reticulum in cardiac myocytes

PubMed Central

Maxwell, Joshua T; Blatter, Lothar A

2012-01-01

The widely accepted paradigm for cytosolic Ca2+ wave propagation postulates a ‘fire-diffuse-fire’ mechanism where local Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca2+ release channels diffuses towards and activates neighbouring release sites, resulting in a propagating Ca2+ wave. A recent challenge to this paradigm proposed the requirement for an intra-SR ‘sensitization’ Ca2+ wave that precedes the cytosolic Ca2+ wave and primes RyRs from the luminal side to CICR. Here, we tested this hypothesis experimentally with direct simultaneous measurements of cytosolic ([Ca2+]i; rhod-2) and intra-SR ([Ca2+]SR; fluo-5N) calcium signals during wave propagation in rabbit ventricular myocytes, using high resolution fluorescence confocal imaging. The increase in [Ca2+]i at the wave front preceded depletion of the SR at each point along the calcium wave front, while during this latency period a transient increase of [Ca2+]SR was observed. This transient elevation of [Ca2+]SR could be identified at individual release junctions and depended on the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). Increased SERCA activity (β-adrenergic stimulation with 1 μm isoproterenol (isoprenaline)) decreased the latency period and increased the amplitude of the transient elevation of [Ca2+]SR, whereas inhibition of SERCA (3 μm cyclopiazonic acid) had the opposite effect. In conclusion, the data provide experimental evidence that local Ca2+ uptake by SERCA into the SR facilitates the propagation of cytosolic Ca2+ waves via luminal sensitization of the RyR, and supports a novel paradigm of a ‘fire-diffuse-uptake-fire’ mechanism for Ca2+ wave propagation in cardiac myocytes. PMID:22988145

Resolving the Inner Arcsecond of the RY Tau Jet with HST

NASA Astrophysics Data System (ADS)

Skinner, Stephen L.; Schneider, P. Christian; Audard, Marc; Güdel, Manuel

2018-03-01

Faint X-ray emission from hot plasma (T x > 106 K) has been detected extending outward a few arcseconds along the optically delineated jets of some classical T Tauri stars including RY Tau. The mechanism and location where the jets are heated to X-ray temperatures are unknown. We present high spatial resolution Hubble Space Telescope (HST) far-ultraviolet long-slit observations of RY Tau with the slit aligned along the jet. The primary objective was to search for C IV emission from warm plasma at T C IV ∼ 105 K within the inner jet (<1″) that cannot be fully resolved by X-ray telescopes. Spatially resolved C IV emission is detected in the blueshifted jet extending outward from the star to 1″ and in the redshifted jet out to 0.″5. C IV line centroid shifts give a radial velocity in the blueshifted jet of ‑136 ± 10 km s‑1 at an offset of 0.″29 (39 au) and deceleration outward is detected. The deprojected jet speed is subject to uncertainties in the jet inclination, but values ≳200 km s‑1 are likely. The mass-loss rate in the blueshifted jet is at least {\\dot{M}}jet,{blue}}=2.3× {10}-9 M ⊙ yr‑1, consistent with optical determinations. We use the HST data along with optically determined jet morphology to place meaningful constraints on candidate jet-heating models including a hot-launch model in which the jet is heated near the base to X-ray temperatures by an unspecified (but probably magnetic) process, and downstream heating from shocks or a putative jet magnetic field.

Comparative Proteomics of Rubber Latex Revealed Multiple Protein Species of REF/SRPP Family Respond Diversely to Ethylene Stimulation among Different Rubber Tree Clones.

PubMed

Tong, Zheng; Wang, Dan; Sun, Yong; Yang, Qian; Meng, Xueru; Wang, Limin; Feng, Weiqiang; Li, Ling; Wurtele, Eve Syrkin; Wang, Xuchu

2017-05-02

Rubber elongation factor (REF) and small rubber particle protein (SRPP) are two key factors for natural rubber biosynthesis. To further understand the roles of these proteins in rubber formation, six different genes for latex abundant REF or SRPP proteins, including REF 138,175,258 and SRPP 117,204,243 , were characterized from Hevea brasiliensis Reyan (RY) 7-33-97. Sequence analysis showed that REFs have a variable and long N-terminal, whereas SRPPs have a variable and long C-terminal beyond the REF domain, and REF 258 has a β subunit of ATPase in its N-terminal. Through two-dimensional electrophoresis (2-DE), each REF/SRPP protein was separated into multiple protein spots on 2-DE gels, indicating they have multiple protein species. The abundance of REF/SRPP proteins was compared between ethylene and control treatments or among rubber tree clones with different levels of latex productivity by analyzing 2-DE gels. The total abundance of each REF/SRPP protein decreased or changed a little upon ethylene stimulation, whereas the abundance of multiple protein species of the same REF/SRPP changed diversely. Among the three rubber tree clones, the abundance of the protein species also differed significantly. Especially, two protein species of REF 175 or REF 258 were ethylene-responsive only in the high latex productivity clone RY 8-79 instead of in RY 7-33-97 and PR 107. Some individual protein species were positively related to ethylene stimulation and latex productivity. These results suggested that the specific protein species could be more important than others for rubber production and post-translational modifications might play important roles in rubber biosynthesis.

Increased Energy Demand during Adrenergic Receptor Stimulation Contributes to Ca(2+) Wave Generation.

PubMed

Bovo, Elisa; Mazurek, Stefan R; de Tombe, Pieter P; Zima, Aleksey V

2015-10-20

While β-adrenergic receptor (β-AR) stimulation ensures adequate cardiac output during stress, it can also trigger life-threatening cardiac arrhythmias. We have previously shown that proarrhythmic Ca(2+) waves during β-AR stimulation temporally coincide with augmentation of reactive oxygen species (ROS) production. In this study, we tested the hypothesis that increased energy demand during β-AR stimulation plays an important role in mitochondrial ROS production and Ca(2+)-wave generation in rabbit ventricular myocytes. We found that β-AR stimulation with isoproterenol (0.1 μM) decreased the mitochondrial redox potential and the ratio of reduced to oxidated glutathione. As a result, β-AR stimulation increased mitochondrial ROS production. These metabolic changes induced by isoproterenol were associated with increased sarcoplasmic reticulum (SR) Ca(2+) leak and frequent diastolic Ca(2+) waves. Inhibition of cell contraction with the myosin ATPase inhibitor blebbistatin attenuated oxidative stress as well as spontaneous SR Ca(2+) release events during β-AR stimulation. Furthermore, we found that oxidative stress induced by β-AR stimulation caused the formation of disulfide bonds between two ryanodine receptor (RyR) subunits, referred to as intersubunit cross-linking. Preventing RyR cross-linking with N-ethylmaleimide decreased the propensity of Ca(2+) waves induced by β-AR stimulation. These data suggest that increased energy demand during sustained β-AR stimulation weakens mitochondrial antioxidant defense, causing ROS release into the cytosol. By inducing RyR intersubunit cross-linking, ROS can increase SR Ca(2+) leak to the critical level that can trigger proarrhythmic Ca(2+) waves. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Low-frequency variations of unknown origin in the Kepler δ Scuti star KIC 5988140 = HD 188774

NASA Astrophysics Data System (ADS)

Lampens, P.; Tkachenko, A.; Lehmann, H.; Debosscher, J.; Aerts, C.; Beck, P. G.; Bloemen, S.; Kochiashvili, N.; Derekas, A.; Smith, J. C.; Tenenbaum, P.; Twicken, J. D.

2013-01-01

Context. The NASA exoplanet search mission Kepler is currently providing a wealth of light curves of ultra-high quality from space. Aims: We used high-quality Kepler photometry and spectroscopic data to investigate the Kepler target and binary candidate KIC 5988140. We aim to interpret the observed variations of KIC 5988140 considering three possible scenarios: binarity, co-existence of δ Sct- and γ Dor-type oscillations, and rotational modulation caused by an asymmetric surface intensity distribution. Methods: We used the spectrum synthesis method to derive the fundamental parameters Teff, log g, [M/H], and v sin i from the newly obtained high-resolution, high S/N spectra. Frequency analyses of both the photometric and the spectroscopic data were performed. Results: The star has a spectral type of A7.5 IV-III and a metallicity slightly lower than that of the Sun. Both Fourier analyses reveal the same two dominant frequencies F1 = 2F2 = 0.688 and F2 = 0.344 d-1. We also detected in the photometry the signal of nine more, significant frequencies located in the typical range of δ Sct pulsation. The light and radial velocity curves follow a similar, stable double-wave pattern which are not exactly in anti-phase but show a relative phase shift of about 0.1 period between the moment of minimum velocity and that of maximum light. Conclusions: Such findings are incompatible with the star being a binary system. We next show that, for all possible (limit) configurations of a spotted surface, the predicted light-to-velocity amplitude ratio is almost two orders larger than the observed value, which pleads against rotational modulation. The same argument also invalidates the explanation in terms of pulsations of type γ Dor (i.e. hybrid pulsations). We confirm the occurrence of various independent δ Sct-type pressure modes in the Kepler light curve. With respect to the low-frequency content, however, we argue that the physical cause of the remaining light and radial velocity variations of this late A-type star remains unexplained by any of the presently considered scenarios. Based on data gathered with NASA's Discovery mission Kepler and with the Hermes spectrograph, installed at the Mercator Telescope, operated on the island of La Palma by the Flemish Community, at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, and with the 2-m Alfred-Jensch telescope of the Thüringer Landessternwarte Tautenburg.Reduced spectra are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/549/A104

Multi-technique investigation of the binary fraction of A-F type candidate hybrid variable stars discovered by Kepler

NASA Astrophysics Data System (ADS)

Lampens, P.; Frémat, Y.; Vermeylen, L.; Sódor, Á.; Skarka, M.; De Cat, P.; Bognár, Zs.; De Nutte, R.; Dumortier, L.; Escorza, A.; Oomen, G. M.; Van de Steene, G.; Kamath, D.; Laverick, M.; Samadi, A.; Triana, S.; Lehmann, H.

2018-02-01

Context. Hundreds of candidate hybrid pulsators of intermediate type A-F were revealed by recent space missions. Hybrid pulsators allow us to study the full stellar interiors, where both low-order p- and high-order g-modes are simultaneously excited. The true hybrid stars must be identified since other processes, related to stellar multiplicity or rotation, might explain the presence of (some) low frequencies observed in their periodograms. Aims: We measured the radial velocities of 50 candidate δ Scuti -γ Doradus hybrid stars from the Kepler mission with the Hermes and ACE spectrographs over a time span of months to years. We aim to derive the fraction of binary and multiple systems and to provide an independent and homogeneous determination of the atmospheric properties and v sin i for all targets. The long(er)-term objective is to identify the (probable) physical cause of the low frequencies. Methods: We computed one-dimensional cross-correlation functions (CCFs) in order to find the best set of parameters in terms of the number of components, spectral type(s), and v sin i for each target. Radial velocities were measured using spectrum synthesis and a two-dimensional cross-correlation technique in the case of double- and triple-lined systems. Fundamental parameters were determined by fitting (composite) synthetic spectra to the normalised median spectra corrected for the appropriate Doppler shifts. Results: We report on the analysis of 478 high-resolution Hermes and 41 ACE spectra of A/F-type candidate hybrid pulsators from the Kepler field. We determined their radial velocities, projected rotational velocities, and atmospheric properties and classified our targets based on the shape of the CCFs and the temporal behaviour of the radial velocities. We derived orbital solutions for seven new systems. Three preliminary long-period orbital solutions are confirmed by a photometric time-delay analysis. Finally, we determined a global multiplicity fraction of 27% in our sample of candidate hybrid stars. Based on observations obtained with the Hermes spectrograph, which is supported by the Research Foundation - Flanders (FWO), Belgium, the Research Council of KU Leuven, Belgium, the Fonds National de la Recherche Scientifique (F.R.S.-FNRS), Belgium, the Royal Observatory of Belgium, the Observatoire de Genève, Switzerland, and the Thüringer Landessternwarte Tautenburg, Germany. Tables 2 and 3 are only, and Tables C.1-C.3 are also, available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A17

Data-Driven Approaches to Empirical Discovery

DTIC Science & Technology

1988-10-31

if nece ry and identify by block number) empirical discovery history of science data-driven heuristics numeric laws theoretical terms scope of laws...to the normative side. Machine Discovery and the History of Science The history of science studies the actual path followed by scientists over the

The γ-ray line signature of the elusive neutrino

NASA Astrophysics Data System (ADS)

Chardonnet, Pascal; Salati, Pierre

1991-06-01

A heavy triplet neutrino may still solve the astronomical missing mass conundrum provided its mass lies in the range between 30 and 80 GeV. If present in the halo of our galaxy, this Majorana neutrino anihilates into monochromatic photons. We show that the resulting γ-ray line signal is well above the diffuse galactic background, due to a fairly large value of the relevant annihilation cross-section. A 1 m2 sr effective area γ-ray detector of the ASTROGAM caliber should accumulate ~ 35 high energy photons on a year period, to be compared with a background noise of 3-6 photons - for a 5% energy resolution. We strongly urge high energy astrophysicists to explore the γ-ray sky up to energies ~ 100 GeV. Should such an intense γ-ray line be discovered, the dark matter mystery would be unravelled. On leave absence from LAPP, B.P. 110, F-74941 Annecyle-Vieux Cedex, France and from Université de Chambéry, F-73000 Chambéry, France.

Novel Carvedilol Analogs that Suppress Store Overload Induced Ca2+ Release

PubMed Central

Smith, Chris D.; Wang, Aixia; Vembaiyan, Kannan; Zhang, Jingqun; Xie, Cuihong; Zhou, Qiang; Wu, Guogen; Wayne Chen, S. R.; Back, Thomas G.

2013-01-01

Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part due to its ability to inhibit store overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization and bioassay of ca. 100 compounds based on the carvedilol motif in order to identify features that correlate with and optimize SOICR inhibition. A single cell bioassay was employed based on the RyR2-R4496C mutant HEK-293 cell line, in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the β-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits. PMID:24124794

Derivation of orthogonal leads from the 12-lead electrocardiogram. Performance of an atrial-based transform for the derivation of P loops.

PubMed

Guillem, M Salud; Sahakian, Alan V; Swiryn, Steven

2008-01-01

The objective of this study was the evaluation of the accuracy of Dower inverse transform for the derivation of the P wave in orthogonal leads. We tested the accuracy of Dower transform on the P wave and compared it with a P-wave-optimized transform in a database of 123 simultaneous recordings of electrocardiograms and vectorcardiograms. This new transform achieved a lower error when we compared derived vs true measured P waves (mean +/- SD, 12.2 +/- 8.0 VRMS) than Dower transform (14.4 +/- 9.5 Root mean squared voltage) and higher correlation values (Rx, 0.93 +/- 0.12; Ry, 0.90 +/- 0.27; Rz, 0.91 +/- 0.18; vs Dower: Rx, 0.88 +/- 0.15; Ry, 0.91 +/- 0.26; Rz, 0.85 +/- 0.23). We conclude that derivation of orthogonal leads for the P wave can be improved by using an atrial-based transform matrix.

Freezing lines of colloidal Yukawa spheres. II. Local structure and characteristic lengths

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

Gapinski, Jacek, E-mail: gapinski@amu.edu.pl; Patkowski, Adam; NanoBioMedical Center, A. Mickiewicz University, Umultowska 85, 61-614 Poznań

Using the Rogers-Young (RY) integral equation scheme for the static pair correlation functions combined with the liquid-phase Hansen-Verlet freezing rule, we study the generic behavior of the radial distribution function and static structure factor of monodisperse charge-stabilized suspensions with Yukawa-type repulsive particle interactions at freezing. In a related article, labeled Paper I [J. Gapinski, G. Nägele, and A. Patkowski, J. Chem. Phys. 136, 024507 (2012)], this hybrid method was used to determine two-parameter freezing lines for experimentally controllable parameters, characteristic of suspensions of charged silica spheres in dimethylformamide. A universal scaling of the RY radial distribution function maximum is shownmore » to apply to the liquid-bcc and liquid-fcc segments of the universal freezing line. A thorough analysis is made of the behavior of characteristic distances and wavenumbers, next-neighbor particle coordination numbers, osmotic compressibility factor, and the Ravaché-Mountain-Streett minimum-maximum radial distribution function ratio.« less

Sub-Saharan Africa: A Focused Strategy for U.S. Policy

DTIC Science & Technology

1998-03-01

a politrcal and economrc chmate that supports trade and investment- The rule of law, a responsibleJudlcm.ry, freedom of religion , expression, and...contmually in conflict, exacerbatmg refugee movements In South Africa, the Zulus compete with other tribal afIiliatrons Whrle corruptron is certainly a

Metodo de Archivar las Observaciones del Comportamiento del Nino, Como Guia para Entenderlo Mejor (Methods of Recording Observations of Children's Behavior, A Guide for Better Understanding)

ERIC Educational Resources Information Center

Stamp, Isla M.

1971-01-01

Copies of the Behaviour Study Technique described in this article may be obtained in English from the Australian Council for Educational Research, Frederick St., Hawthorn, Victoria, Australia 3122. (RY)

U.S. EPA, Pesticide Product Label, FLEAGO THE MAGIC CRYSTAL, 07/09/1997

EPA Pesticide Factsheets

2011-04-21

... Fleago The Magic Crystal '~~~:ul~~i~;~i~~!;~i~~fat~~I~~n~w~~~~: W~?~:~iA~~~~~r~Y '~~;: ... lhe Magic Crystal ...

They Made Black History.

ERIC Educational Resources Information Center

Elward, Thomas J.

1981-01-01

Reviews the history of Black music education in the public schools of Washington, D.C., from 1869 through the 1920s. Appended (on pp38-39) are historical notes on Black composers James Weldon Johnson and John Rosamond Johnson, and their song "Lift Ev'ry Voice and Sing." (Author/SJL)

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

PubMed

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is one of four residues that are important for receptor functional integrity, maintaining the binding pocket conformation and allowing rotation following ligand binding. Conclusion This novel dominant negative variant confirms the important role of R265 in EL3 in the functional integrity of P2Y12R, and suggests that pathologic heterodimer formation may underlie this family bleeding phenotype. © 2017 International Society on Thrombosis and Haemostasis.

Defense Planning for National Security: Navigation Aids for the Mystery Tour

DTIC Science & Technology

2014-03-01

to provide in the necessary quantity. 2. Training: superior training regimes are not en- tirely reliable as keys to victory. Although rigorous... eccentric misbehavior, the question of how much tolerance is permissible should not be ignored. The reason is not simply academic pedant- ry. A single

Water use efficiency by switchgrass compared to a native grass or a native grass alfalfa mixture

USDA-ARS?s Scientific Manuscript database

Development of sustainable cellulosic biofuel systems requires knowing the water use efficiency (WUE) of potential bioenergy crops. Impact of early and late season droughts on WUE and soil water deficits were evaluated in switchgrass (Panicum virgatum L.), western wheatgrass (Pascopyrum smithii (Ry...

U.S. EPA, Pesticide Product Label, PHOSDRIN 4E, 07/23/1970

EPA Pesticide Factsheets

2011-04-14

... of tl'''i('if~: til lah'lratf'ry :uHmals and to plant ..... and of re .... jrh,t· ... 1111 (qud crill''' , an.t UP"fl rt.'pqrt ... 4 'f fit'lel l'XJU'Tlf'rlf'I' ',· . t'" hr.,"" n.,t h(>('11 ...

Worldwide Report, Arms Control

DTIC Science & Technology

1986-01-02

contentedly. Since April, when the Franch plan for European technology was launched, he has traveled to the capitals of 18 countries, among them the...territo- cheering throng at Queen’s Park’: ted $50 million for food aidt for .ry. that the Canadian peace move-, Africa thilss.mmer .. Lubbers said the

Laboratory and Field Evaluation of SS220 and Deet Against Mosquitoes in Queensland, Australia

DTIC Science & Technology

2009-01-01

Australian Army Malaria Institute, Gallipoli Bar- racks, Enoggera, Queensland 4051, Australia. 2 Invasive Insect Biocontrol and Behavior Laborato- ry...Invasive Insect Biocontrol and Behavior Laboratory (Beltsville, MD; Klun et al. 2003). A 20% solution (V/V) of each chemical in absolute ethanol was used

Heterogeneous Integration Technology

DTIC Science & Technology

2017-05-19

Distribution A. Approved for public release; distribution unlimited. (APRS-RY-17-0383) Heterogeneous Integration Technology Dr. Burhan...2013 and 2015 [4]. ...................................... 9 Figure 3: 3D integration of similar or diverse technology components follows More Moore and...10 Figure 4: Many different technologies are used in the implementation of modern microelectronics systems can benefit from

Integration Framework for Heterogeneous Analysis Components: Building a Context Aware Virtual Analyst

DTIC Science & Technology

2014-11-01

understands commands) modes are supported. By default, Julius comes with the Japanese language support. English acoustic and language models are...GUI, natura atar represent gue managem s the activitie ystem to und ry that suppo the Dialogu der to call arning (ML) learning ca r and feedb

Hot Accretion Spots and Nitrogen Enhancement in Algol-Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine J.

2013-07-01

The shock from the impact of a gas stream onto the photosphere of a mass gainer in an Algol system is expected to produce a hot spot and also heat circumstellar material that is splashed from the impact site. Furthermore in some cases we expect the stripped-down mass loser (a late-type subgiant) to be nitrogen rich and carbon poor if CNO-processed material is currently being transferred. I will present observational evidence from the Kepler and FUSE spacecrafts for the presence of hot spots and discuss their behavior. FUSE observations of Algols that convincingly show that the gas stream material from some Algol secondaries is N-enhanced and virtually devoid of carbon is also presented. From Kepler data we have identified a long-term phenomenon in which the relative brightness of the quadrature light varies by a few percent and numerically reverses over a time scale of about a 100-400 days. We call the systems T/L (trailing hemisphere/leading hemisphere) variables. Such behavior has never been identified from ground-based photometry. WX Draconis (A8 + K0 IV, P = 1.80 d), a system whose primary displays delta Scuti-like pulsations, is the prototype. The Kepler light curves are being modeled with the latest version of the Wilson-Devinney program that includes the capability of treating migrating hot/cool spots. I will discuss whether the T/L behavior is likely due to a migrating hot accretion spot on the primary or variability in a large cool-spotted area on the secondary. From archival FUSE data we have confirmed the presence of a hot accretion spot in the Algol system U Cephei and present information on the spot parameters/behavior and conditions in a splash plasma from the impact site. Kepler and archival FUSE observations continue to provide important information on the nature of the component stars in Algol systems and the detailed physics of mass transfer, especially the role of accretion hot spots. We are grateful for support from NASA grants NNX11AC78G and NNX12AE44G.

Hour-Scale Variability in NGC 663 and NGC 1960

NASA Astrophysics Data System (ADS)

Souza, Steven P.; Garcia Soto, Aylin; Wong, Hallee

2016-06-01

Since 2010 we have been monitoring massive emission-line (mainly Be) stars in young open clusters using narrowband imaging at Hα (656nm) and the nearby continuum (645nm) (Souza, Davis, and Teich 2013, BAAS. 45, PM354.22; Souza, Beltz-Mohrmann, and Sami 2014. JAAVSO, 42, 154). To supplement longer-timescale data taken at Williams College we obtained high-cadence observations, in both filters, of NGC 663 on the night of 12/10/15, and of NGC 1960 on the nights of 12/10/14, 1/23/15, 1/25/15, 11/11/15, and 12/13/15 at the 0.5m ARCSAT at Apache Point Observatory. After raw magnitude extraction using Aperture Photometry Tool (Laher et al. 2012, PASP, 124, 737), we used inhomogeneous ensemble photometry (Bhatti et al., 2010, ApJ Supp., 186, 233) to correct for transparency and seeing variations. The NGC 663 field is crowded; of 29 known Be stars in the observed field, 10 have nearby interferers. None of the remaining 19 Be stars showed significant variation during ~5.5 hours of observation. 1σ uncertainty estimates range from 0.02mag at R~10 to 0.15mag at R~14. To verify the observing and reduction procedure, we recovered hour-scale variability in known variables BY Cas (δ Cephei type, ~0.05mag decline) and V1155 Cas (β Cephei type, ~0.04mag amplitude). In NGC 1960, of 5 known and suspect Be stars observed, two not previously reported as variable (BD+34 1110 and USNOB1.0 1241-0103450) showed irregular variation on timescales of hours. In NGC 1960 we also report the incidental discovery of two non-Be suspect variables: a likely eclipsing binary (0.07mag), and a possible δ Scuti star (maximum amplitude ~0.02mag). We gratefully acknowledge support for student research from NSF grant AST-1005024 to the Keck Northeast Astronomy Consortium, and the Office of the Dean of Faculty and the DIII Research Funding Committee of Williams College. Based on observations obtained with Apache Point Observatory's 0.5-m Astrophysical Research Consortium Small Aperture Telescope.

New multi-site observations of the delta Scuti stars BS and BT Cancri. Results of the STEPHI VII campaign on the Praesepe cluster

NASA Astrophysics Data System (ADS)

Hernandez, M. M.; Michel, E.; Belmonte, J. A.; Jiang, S. Y.; Alvarez, M.; Chevreton, M.; Paparo, M.; Kjeldsen, H.; Bauduin, D.; Fromage, J.; Goupil, M. J.; Li, Z. P.; Liu, Y. Y.; Mangeney, A.; Massacrier, G.; Ringot, O.; Cortes, T. Roca; Servan, B.; Vidal, I.

1998-09-01

New observations of BS and BT Cnc were performed during the STEPHI VII campaign in 1996 February. An overall run of 115 hours of data was collected. Different methods have been used to analyse the time series, bringing the detection of 2 frequencies for BT Cnc and 3 frequencies for BS Cnc above the 99% confidence level. A comparison with the literature reveals that the dominant mode of BT Cnc ( ~ 9.8 c/d) has kept excited over tens of years, while the secondary modes have not been the same all the time. However, during the very last years the two frequencies detected by us have been the only ones noticeably excited in the spectrum.

78 FR 76098 - Rail Transportation of Grain, Rate Regulation Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

...) Opening 4-5, Rate Regulation Reforms, EP 715; Alliance for Rail Competition, Montana Wheat & Barley... Producers Board, and Washington Grain Commission Opening 6-12, Rate Regulation Reforms, EP 715. \\3\\ NGFA Opening 3-4, Rate Regulation Reforms, EP 715. \\4\\ BNSF Ry. Co. Reply 10, Rate Regulation Reforms, EP 715...

Lighting Control Systems Handbook.

DTIC Science & Technology

1985-06-01

cost, both initial and operating. Initially, the control system designer must collect in- formation and then study and weigh several areas including...8217odLe 045. Pearl Harbor. III: Code 11 Pearl Harbor ar ho I ir I L ’ odk 402. R IYI& [’. Plearl II arbor I II: Li bra ry. Pearl HaIitrbor. I ai

Mathematical Inqu[ee]ry: Beyond "Add-Queers-and-Stir" Elementary Mathematics Education

ERIC Educational Resources Information Center

Rands, Kathleen

2009-01-01

While elementary educators have developed queer pedagogies and perspectives in many subjects from reading to music, science to English as a second language, queer perspectives on elementary mathematics education are remarkably absent. This article differentiates between two common uses of the term "queer" and delineates two sets of approaches…

Investigation of Coating Compounds and Adhesives for Self-Supporting Collapsible Fuel Storage Tanks.

DTIC Science & Technology

1977-06-01

guideline value of 25 lbs/ in. These low values were obtained because the prima ry mode of failure was between coats of the polyether coat- ing compound...method was developed for spray coating fabric substrates wi th one-shot pol yurethane materia ls yielding a coated fabric. Microscopic examination

77 FR 26603 - Central Midland Railway Company and Progressive Rail Inc.-Intra-Corporate Family Transaction...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

... Railway Company and Progressive Rail Inc.--Intra- Corporate Family Transaction Exemption Central Midland... verified notice of exemption under 49 CFR 1180.2(d)(3) and 1180.2(d)(6) for an intra-corporate family...). \\2\\ See Progressive Rail Inc.--Intra-Corporate Family Transaction Exemption--Airlake Terminal Ry., FD...

Academic Pipeline and Futures Lab

DTIC Science & Technology

2016-02-01

AFRL-RY-WP-TR-2015-0186 ACADEMIC PIPELINE AND FUTURES LAB Brian D. Rigling Wright State University FEBRUARY 2016...DD-MM-YY) 2. REPORT TYPE 3. DATES COVERED (From - To) February 2016 Final 12 June 2009 – 30 September 2015 4. TITLE AND SUBTITLE ACADEMIC ...6 3 WSU ACADEMIC PIPELINE AND LAYERED SENSING FUTURES LAB (prepared by K

Betalain profile, phenolic content, and color characterization of different parts and varieties of Opuntia ficus-indica.

PubMed

Cejudo-Bastante, María Jesús; Chaalal, Makhlouf; Louaileche, Hayette; Parrado, Juan; Heredia, Francisco J

2014-08-20

Three different varieties of Opuntia ficus-indica (R, red; Y, yellow; RY, red-yellow) have been considered in this study. Attention was focused on differential tristimulus colorimetry and on the analysis of individual betalains (HPLC-DAD-ESI-ToF-MS) and phenolic content, scarcely previously reported in these kinds of samples. The importance of this research stems from the elucidation of the parts and varieties of cactus pear more optimal for use as natural colorants and sources of phenolics and betalains. Thus, the RY pulp was appropriate to obtain colorants with high color intensity (C*(ab) = 66.5), whereas the whole Y fruit and R pulp reached powerful and stable yellow and red colors, respectively (C*(ab)/h(ab), 57.1/84.7 and 61.1°/81.8°). This choice was also based on the visually appreciable differences (ΔE*(ab) > 5) among samples, mainly quantitative (%Δ(2)L, %Δ(2)C). In addition, seeds of all Opuntia varieties showed significantly (p < 0.05) similar phenolic content (around 23.3 mg/g) and color characteristics.

Esophagogastrostomy plus gastrojejunostomy: a novel reconstruction procedure after curative resection for proximal gastric cancer.

PubMed

Chen, Shicai; Li, Jianchang; Liu, Haiying; Zeng, Jun; Yang, Guohua; Wang, Jin; Lu, Weiqun; Yu, Nanrong; Huang, Zhiliang; Xu, Houwei; Zeng, Xiang

2014-03-01

The choice of surgical strategy for patients with proximal gastric cancer remains controversial. In this study, we recommend that a new reconstruction procedure be performed following proximal gastrectomy. We conducted a retrospective study involving 71 patients who underwent gastrectomy for proximal gastric cancer. Clinicopathological features, postoperative complications, nutritional status, and overall survival (OS) rate were compared among three different reconstruction approaches. There were 34 cases of proximal gastrectomy followed by esophagogastrostomy reconstruction (EG), 16 cases of total gastrectomy and Roux-en Y reconstruction (RY) and 21 cases of proximal gastrectomy followed by esophagogastrostomy plus gastrojejunostomy reconstruction (EGJ). Though the clinicopathological features, the nutritional status and OS rate were similar among the three groups of patients, the incidence of reflux esophagitis was significantly higher in the EG group (35.3%) than the RY (6.2%) and EGJ (9.6%) groups(P < 0.05). Few EGJ patients suffered from either reflux esophagitis or anastomotic stenosis. The EGJ reconstruction method helps to resolve the syndrome of reflux esophagitis. Our data indicates that it is a simple, safe, and effective reconstruction procedure for PGC.

Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency

PubMed Central

Oyama, Mark A.; Reiken, Steve; Lehnart, Stephan E.; Chittur, Sridar V.; Meurs, Kathryn M.; Stern, Joshua; Marks, Andrew R.

2010-01-01

Objective To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). Animals Thirteen Boxer dogs with ARVC. Materials and methods Tissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing. Results In cardiomyopathic Boxer dogs, myocardial calstabin2 mRNA and protein were significantly decreased as compared to healthy control dogs (calstabin2 protein normalized to tetrameric cardiac ryanodine receptor (RyR2) complex: affected, 0.51 ± 0.04; control, 3.81 ± 0.22; P < 0.0001). Calstabin2 deficiency in diseased dog hearts was associated with a significantly increased open probability of single RyR2 channels indicating intracellular Ca2+ leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations. Conclusions Calstabin2 deficiency is a potential mechanism of Ca2+ leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC. PMID:18515204

Underlying mechanism of the contractile dysfunction in atrophied ventricular myocytes from a murine model of hypothyroidism.

PubMed

Montalvo, Dolores; Pérez-Treviño, Perla; Madrazo-Aguirre, Katheryne; González-Mondellini, Fabio A; Miranda-Roblero, Hipólito O; Ramonfaur-Gracia, Diego; Jacobo-Antonio, Mariana; Mayorga-Luna, Maritza; Gómez-Víquez, Norma L; García, Noemí; Altamirano, Julio

2018-06-01

Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca 2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca 2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca 2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (D mit ) and energy availability, is unclear. Therefore, in a rat model of Hypo, we aimed to characterize systolic and diastolic Ca 2+ signaling, T-T remodeling, D mit , citrate synthase (CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca 2+ (19%) and blunted Ca 2+ transient amplitude (41%). Moreover, assessing the rate of SR Ca 2+ release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca 2+ transients. However, dRel/dt persisted during Ca 2+ transient relaxation due to abundant late Ca 2+ sparks. Isoproterenol significantly up-regulated systolic Ca 2+ cycling. T-T were unchanged, hence, cannot explain staggered Ca 2+ transients and altered dRel/dt. Therefore, we suggest that these might be caused by RyR2 clusters desynchronization, due to diminished Ca 2+ -dependent sensitivity of RyR2, which also caused a decrease in diastolic SR Ca 2+ leak. Furthermore, D mit was unchanged and CS activity slightly decreased (14%), however, the ratio phosphocreatine/ATP did not change, therefore, energy deficiency cannot account for Ca 2+ and contractility dysregulation. We conclude that decreased SR Ca 2+ , due to slower SERCA, disrupts systolic RyR2 synchronization, and this underlies CD. Copyright © 2018 Elsevier Ltd. All rights reserved.

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

PubMed

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

A Low-Dose β1-Blocker in Combination with Milrinone Improves Intracellular Ca2+ Handling in Failing Cardiomyocytes by Inhibition of Milrinone-Induced Diastolic Ca2+ Leakage from the Sarcoplasmic Reticulum

PubMed Central

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

Objectives The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. Background The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca2+ handling in heart failure remains unclear. Methods We investigated the effect of milrinone plus landiolol on intracellular Ca2+ transient (CaT), cell shortening (CS), the frequency of diastolic Ca2+ sparks (CaSF), and sarcoplasmic reticulum Ca2+ concentration ({Ca2+}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). Results In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. Conclusion A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca2+ leak. PMID:25614983

The contribution of inositol 1,4,5-trisphosphate and ryanodine receptors to agonist-induced Ca(2+) signaling of airway smooth muscle cells.

PubMed

Bai, Yan; Edelmann, Martin; Sanderson, Michael J

2009-08-01

The relative contribution of inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and ryanodine receptors (RyRs) to agonist-induced Ca(2+) signaling in mouse airway smooth muscle cells (SMCs) was investigated in lung slices with phase-contrast or laser scanning microscopy. At room temperature (RT), methacholine (MCh) or 5-hydroxytryptamine (5-HT) induced Ca(2+) oscillations and an associated contraction in small airway SMCs. The subsequent exposure to an IP(3)R antagonist, 2-aminoethoxydiphenyl borate (2-APB), inhibited the Ca(2+) oscillations and induced airway relaxation in a concentration-dependent manner. 2-APB also inhibited Ca(2+) waves generated by the photolytic release of IP(3). However, the RyR antagonist ryanodine had no significant effect, at any concentration, on airway contraction or agonist- or IP(3)-induced Ca(2+) oscillations or Ca(2+) wave propagation. By contrast, a second RyR antagonist, tetracaine, relaxed agonist-contracted airways and inhibited agonist-induced Ca(2+) oscillations in a concentration-dependent manner. However, tetracaine did not affect IP(3)-induced Ca(2+) release or wave propagation nor the Ca(2+) content of SMC Ca(2+) stores as evaluated by Ca(2+)-release induced by caffeine. Conversely, both ryanodine and tetracaine completely blocked agonist-independent slow Ca(2+) oscillations induced by KCl. The inhibitory effects of 2-APB and absence of an effect of ryanodine on MCh-induced airway contraction or Ca(2+) oscillations of SMCs were also observed at 37 degrees C. In Ca(2+)-permeable SMCs, tetracaine inhibited agonist-induced contraction without affecting intracellular Ca(2+) levels indicating that relaxation also resulted from a reduction in Ca(2+) sensitivity. These results indicate that agonist-induced Ca(2+) oscillations in mouse small airway SMCs are primary mediated via IP(3)Rs and that tetracaine induces relaxation by both decreasing Ca(2+) sensitivity and inhibiting agonist-induced Ca(2+) oscillations via an IP(3)-dependent mechanism.

Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel.

PubMed

Kawakami, M; Okabe, E

1998-03-01

The ryanodine receptor Ca2+ channel (RyRC) constitutes the Ca2+-release pathway in sarcoplasmic reticulum (SR) of cardiac muscle. A direct mechanical and a Ca2+-triggered mechanism (Ca2+-induced Ca2+ release) have been proposed to explain the in situ activation of Ca2+ release in cardiac muscle. A variety of chemical oxidants have been shown to activate RyRC; however, the role of modification induced by oxygen-derived free radicals in pathological states of the muscle remains to be elucidated. It has been hypothesized that oxygen-derived free radicals initiate Ca2+-mediated functional changes in or damage to cardiac muscle by acting on the SR and promoting an increase in Ca2+ release. We confirmed that superoxide anion radical (O2-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles; hypoxanthine-xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+-ATPase activity. Current fluctuations through single Ca2+-release channels have been monitored after incorporation into planar phospholipid bilayers. We demonstrate that activation of the channel by O2- is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2--triggered Ca2+ release through the RyRC. For the first time, we show that O2- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2-. The decreased calmodulin content induced by oxygen-derived free radicals, especially O2-, is a likely mechanism of accumulation of cytosolic Ca2+ (due to increased Ca2+ release from SR) after reperfusion of the ischemic heart.

Functional analysis of a frame-shift mutant of the dihydropyridine receptor pore subunit (α1S) expressing two complementary protein fragments

PubMed Central

Ahern, Chris A; Vallejo, Paola; Mortenson, Lindsay; Coronado, Roberto

2001-01-01

Background The L-type Ca2+ channel formed by the dihydropyridine receptor (DHPR) of skeletal muscle senses the membrane voltage and opens the ryanodine receptor (RyR1). This channel-to-channel coupling is essential for Ca2+ signaling but poorly understood. We characterized a single-base frame-shift mutant of α1S, the pore subunit of the DHPR, that has the unusual ability to function voltage sensor for excitation-contraction (EC) coupling by virtue of expressing two complementary hemi-Ca2+ channel fragments. Results Functional analysis of cDNA transfected dysgenic myotubes lacking α1S were carried out using voltage-clamp, confocal Ca2+ indicator fluoresence, epitope immunofluorescence and immunoblots of expressed proteins. The frame-shift mutant (fs-α1S) expressed the N-terminal half of α1S (M1 to L670) and the C-terminal half starting at M701 separately. The C-terminal fragment was generated by an unexpected restart of translation of the fs-α1S message at M701 and was eliminated by a M701I mutation. Protein-protein complementation between the two fragments produced recovery of skeletal-type EC coupling but not L-type Ca2+ current. Discussion A premature stop codon in the II-III loop may not necessarily cause a loss of DHPR function due to a restart of translation within the II-III loop, presumably by a mechanism involving leaky ribosomal scanning. In these cases, function is recovered by expression of complementary protein fragments from the same cDNA. DHPR-RyR1 interactions can be achieved via protein-protein complementation between hemi-Ca2+ channel proteins, hence an intact II-III loop is not essential for coupling the DHPR voltage sensor to the opening of RyR1 channel. PMID:11806762

Projective limits of state spaces IV. Fractal label sets

NASA Astrophysics Data System (ADS)

Lanéry, Suzanne; Thiemann, Thomas

2018-01-01

Instead of formulating the state space of a quantum field theory over one big Hilbert space, it has been proposed by Kijowski (1977) to represent quantum states as projective families of density matrices over a collection of smaller, simpler Hilbert spaces (see Lanéry (2016) [1] for a concise introduction to this formalism). One can thus bypass the need to select a vacuum state for the theory, and still be provided with an explicit and constructive description of the quantum state space, at least as long as the label set indexing the projective structure is countable. Because uncountable label sets are much less practical in this context, we develop in the present article a general procedure to trim an originally uncountable label set down to countable cardinality. In particular, we investigate how to perform this tightening of the label set in a way that preserves both the physical content of the algebra of observables and its symmetries. This work is notably motivated by applications to the holonomy-flux algebra underlying Loop Quantum Gravity. Building on earlier work by Okołów (2013), a projective state space was introduced for this algebra in Lanéry and Thiemann (2016). However, the non-trivial structure of the holonomy-flux algebra prevents the construction of satisfactory semi-classical states (Lanéry and Thiemann, 2017). Implementing the general procedure just mentioned in the case of a one-dimensional version of this algebra, we show how a discrete subalgebra can be extracted without destroying universality nor diffeomorphism invariance. On this subalgebra, quantum states can then be constructed which are more regular than was possible on the original algebra. In particular, this allows the design of semi-classical states whose semi-classicality is enforced step by step, starting from collective, macroscopic degrees of freedom and going down progressively toward smaller and smaller scales.

Burnout syndrome among dental students: a short version of the "Burnout Clinical Subtype Questionnaire" adapted for students (BCSQ-12-SS).

PubMed

Montero-Marin, Jesus; Monticelli, Francesca; Casas, Marina; Roman, Amparo; Tomas, Inmaculada; Gili, Margarita; Garcia-Campayo, Javier

2011-12-12

Burnout has been traditionally defined in relation to the dimensions of "exhaustion", "cynicism", and "inefficiency". More recently, the Burnout Clinical Subtype Questionnaire (BCSQ-12) further established three different subtypes of burnout: the "frenetic" subtype (related to "overload"), the "under-challenged" subtype (related to "lack of development"), and the "worn-out" subtype (related to "neglect"). However, to date, these definitions have not been applied to students. The aims of this research were (1) to adapt a Spanish version of the BCSQ-12 for use with students, (2) to test its factorial validity, internal consistency, convergent and discriminant validity, and (3) to assess potential socio-demographic and occupational risk factors associated with the development of the subtypes. We used a cross-sectional design on a sample of dental students (n = 314) from Santiago and Huesca universities (Spain). Participants completed the Burnout Clinical Subtype Questionnaire Student Survey (BCSQ-12-SS), the Maslach Burnout Inventory Student Survey (MBI-SS), and a series of socio-demographic and occupational questions formulated for the specific purpose of this study. Data were subjected to exploratory factor analysis (EFA) using the principal component method with varimax orthogonal rotation. To assess the relations with the criterion, we calculated the Pearson correlation coefficient (r), multiple correlation coefficient (R(y.123)), and the coefficient of determination (R(2)(y.123)). To assess the association between the subtypes and the socio-demographic variables, we examined the adjusted odds ratio (OR) obtained from multivariate logistic regression models. Factorial analyses supported the theoretical proposition of the BCSQ-12-SS, with α-values exceeding 0.80 for all dimensions. The "overload-exhaustion" relation was r = 0.59 (p < 0.001), "lack of development"-"cynicism", r = 0.49 (p < 0.001), "neglect"-"inefficiency", r = 0.47 (p < 0.001). The "overload"-"lack of development" relation was r = 0.21 (p < 0.001), "overload"-"neglect", r = 0.20 (p < 0.001), and "lack of development"-"neglect", r = 0.38 (p < 0.001). The BCSQ-12-SS explained 38.44% of the variability in "exhaustion", (R(y.123) = 0.62), 30.25% in "cynicism" (R(y.123) = 0.55), and 26.01% in "inefficiency" (R(y.123) = 0.51). "Hours spent on studying" was found to be associated with "overload" (p = 0.001), "campus" with "lack of development" (p = 0.013), and "failed subjects" with "neglect" (p = 0.011). The results support the definition of burnout as established by the BCSQ-12-SS. As such, the BCSQ-12-SS can be used for the recognition of clinical profiles and for the suggestion of potential intervention strategies specific to the characteristics of each particular case.

Burnout syndrome among dental students: a short version of the "Burnout Clinical Subtype Questionnaire" adapted for students (BCSQ-12-SS)

PubMed Central

2011-01-01

Background Burnout has been traditionally defined in relation to the dimensions of "exhaustion", "cynicism", and "inefficiency". More recently, the Burnout Clinical Subtype Questionnaire (BCSQ-12) further established three different subtypes of burnout: the "frenetic" subtype (related to "overload"), the "under-challenged" subtype (related to "lack of development"), and the "worn-out" subtype (related to "neglect"). However, to date, these definitions have not been applied to students. The aims of this research were (1) to adapt a Spanish version of the BCSQ-12 for use with students, (2) to test its factorial validity, internal consistency, convergent and discriminant validity, and (3) to assess potential socio-demographic and occupational risk factors associated with the development of the subtypes. Method We used a cross-sectional design on a sample of dental students (n = 314) from Santiago and Huesca universities (Spain). Participants completed the Burnout Clinical Subtype Questionnaire Student Survey (BCSQ-12-SS), the Maslach Burnout Inventory Student Survey (MBI-SS), and a series of socio-demographic and occupational questions formulated for the specific purpose of this study. Data were subjected to exploratory factor analysis (EFA) using the principal component method with varimax orthogonal rotation. To assess the relations with the criterion, we calculated the Pearson correlation coefficient (r), multiple correlation coefficient (Ry.123), and the coefficient of determination (R2y.123). To assess the association between the subtypes and the socio-demographic variables, we examined the adjusted odds ratio (OR) obtained from multivariate logistic regression models. Results Factorial analyses supported the theoretical proposition of the BCSQ-12-SS, with α-values exceeding 0.80 for all dimensions. The "overload-exhaustion" relation was r = 0.59 (p < 0.001), "lack of development"-"cynicism", r = 0.49 (p < 0.001), "neglect"-"inefficiency", r = 0.47 (p < 0.001). The "overload"-"lack of development" relation was r = 0.21 (p < 0.001), "overload"-"neglect", r = 0.20 (p < 0.001), and "lack of development"-"neglect", r = 0.38 (p < 0.001). The BCSQ-12-SS explained 38.44% of the variability in "exhaustion", (Ry.123 = 0.62), 30.25% in "cynicism" (Ry.123 = 0.55), and 26.01% in "inefficiency" (Ry.123 = 0.51). "Hours spent on studying" was found to be associated with "overload" (p = 0.001), "campus" with "lack of development" (p = 0.013), and ""failed subjects" with "neglect" (p = 0.011). Conclusions The results support the definition of burnout as established by the BCSQ-12-SS. As such, the BCSQ-12-SS can be used for the recognition of clinical profiles and for the suggestion of potential intervention strategies specific to the characteristics of each particular case. PMID:22151576

KIC 9533489: a genuine γ Doradus - δ Scuti Kepler hybrid pulsator with transit events

NASA Astrophysics Data System (ADS)

Bognár, Zs.; Lampens, P.; Frémat, Y.; Southworth, J.; Sódor, Á.; De Cat, P.; Isaacson, H. T.; Marcy, G. W.; Ciardi, D. R.; Gilliland, R. L.; Martín-Fernández, P.

2015-09-01

Context. Several hundred candidate hybrid pulsators of type A-F have been identified from space-based observations. Their large number allows both statistical analyses and detailed investigations of individual stars. This offers the opportunity to study the full interior of the genuine hybrids, in which both low radial order p- and high-order g-modes are self-excited at the same time. However, a few other physical processes can also be responsible for the observed hybrid nature, related to binarity or to surface inhomogeneities. The finding that most δ Scuti stars also show long-period light variations represents a real challenge for theory. Aims: We aim at determining the pulsation frequencies of KIC 9533489, to search for regular patterns and spacings among them, and to investigate the stability of the frequencies and the amplitudes. An additional goal is to study the serendipitously detected transit events: is KIC 9533489 the host star? What are the limitations on the physical parameters of the involved bodies? Methods: We performed a Fourier analysis of all the available Kepler light curves. We investigated the frequency and period spacings and determined the stellar physical parameters from spectroscopic observations. We also modelled the transit events. Results: The Fourier analysis of the Kepler light curves revealed 55 significant frequencies clustered into two groups, which are separated by a gap between 15 and 27 d-1. The light variations are dominated by the beating of two dominant frequencies located at around 4 d-1. The amplitudes of these two frequencies show a monotonic long-term trend. The frequency spacing analysis revealed two possibilities: the pulsator is either a highly inclined moderate rotator (v ≈ 70 km s-1, i> 70°) or a fast rotator (v ≈ 200 km s-1) with i ≈ 20°. The transit analysis disclosed that the transit events that occur with a ≈197 d period may be caused by a 1.6 RJup body orbiting a fainter star, which would be spatially coincident with KIC 9533489.

Alcohol Abuse Disorders Among U.S. Service Members With Mild Traumatic Brain Injury

DTIC Science & Technology

2011-02-01

the wounded from Iraq and Afghanistan. New Engl J Med 2004; 351: 2471 - 5. 7. Okie S: Traumatic brain injury in the war zone. New Engl J Med 2005...Alcohol and drug dependence and psychiatric comorbidity. Br J Psychiat ry 2001; 179 : 432- 7. 21 . Tonneson H, Rosenberg J, Nielsen HJ, et al

Air Force Research Laboratory Sensors Directorate Leadership Legacy, 1960-2011

DTIC Science & Technology

2011-03-01

AFRL -RY-WP-TM-2011-1017 AIR FORCE RESEARCH LABORATORY SENSORS DIRECTORATE LEADERSHIP LEGACY, 1960-2011 Compiled by Raymond C. Rang...Structures Divi- sion, Space Vehicles Directorate, Air Force Research Laboratory , Kirtland AFB, N.M. 7. March 1998 - July 1999, Chief, Integration and... Research Laboratory ( AFRL ), and Deputy Director of the Sensors Direc- torate, Air Force Research

Multi-Stage Maximum Likelihood Target Estimator

DTIC Science & Technology

2006-03-31

Compute the range at ti with respect to 19 the sensor associated with the ith 20 measurement (Ri): 23 1 R, = VRx ’+ Ryl’ (3 2 2.) Compute the range...the ith measurement 12 ii. Compute the range at tj with respect tothe 13 sensor associated with the ith measurement (R4) 14 = VRx + Ry (323) 15 iii

29 CFR 782.8 - Special classes of carriers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... subject to its jurisdiction. (New Pittsburgh Coal Co. v. Hocking Valley Ry. Co., 24 I.C.C. 244; Corona Coal Co. v. Secretary of War, 69 I.C.C. 389; Bunker Coal from Alabama to Gulf Ports, 227 I.C.C. 485.) The intrastate delivery of chandleries, including cordage, canvas, repair parts, wire rope, etc., to...

29 CFR 782.8 - Special classes of carriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... subject to its jurisdiction. (New Pittsburgh Coal Co. v. Hocking Valley Ry. Co., 24 I.C.C. 244; Corona Coal Co. v. Secretary of War, 69 I.C.C. 389; Bunker Coal from Alabama to Gulf Ports, 227 I.C.C. 485.) The intrastate delivery of chandleries, including cordage, canvas, repair parts, wire rope, etc., to...

Patterns of Creation and Discovery: An Analysis of Defense Laboratory Patenting and Innovation

DTIC Science & Technology

2013-01-01

Manufacturing Material science, manufacturing processes AFRL RY Sensors Radio frequency and electro-optic sensing, sensor fusion, network-enabled...MONITOR’S ACRONYM(S) 11 . SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited...2.2 A DOD-relevant definition of innovation as use .............................................................................. 11 2.3 Patent trends

Adapting the ADAM Manikin Technology for Injury Probability Assessment

DTIC Science & Technology

1992-02-19

Benson, J.B., Holstein , G.L., Melvin, J.W. Whole Body Response Research Program. Ann Arbor, MI, University of Michigan, Highway Safety Research...Liver Laceration I Fatal 25 227 9. UNKNOWN - COW ’ Aassiou" Ntoobor of 14my~ PAft Irni Type [ rid Ca ry Rados Neck tam 2nd D•s"* I Minimwl 4 Neck

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

EPA Science Inventory

CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

Lift Ev'ry Voice: The Resounding Experiences of Black Male Student-Athletes at a California Community College

ERIC Educational Resources Information Center

McClellan, Michael L.

2013-01-01

Black male student-athletes are entering the California community college (CCC) system at an unprecedented rate. CCCs have become a repository for Black males that have aspirations of competing in the National Collegiate Athletic Association (NCAA) Division I member institutions. This historically disenfranchised subgroup of students is required…

Amplitude Variability in gamma Dor and delta Sct Stars Observed by Kepler

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

Guzik, Joyce Ann; Kosak, Mary Katherine; Bradley, Paul Andrew

2015-08-17

The NASA Kepler spacecraft data revealed a large number of new multimode nonradially pulsating gamma Dor and delta Sct variable stars. The Kepler high-precision long time-series photometry makes it possible to study amplitude variations of the frequencies, and recent literature on amplitude and frequency variations in nonradially pulsating variables is summarized. Several methods are applied to study amplitude variability in about a dozen gamma Doradus or delta Scuti candidate variable stars observed for several quarters as part of the Kepler Guest Observer program. The magnitude and timescale of the amplitude variations are discussed, along with the presence or absence ofmore » correlations between amplitude variations for different frequencies of a given star. Proposed causes of amplitude spectrum variability that will require further investigation are also discussed.« less

Long-term infrared monitoring of stellar sources from earth orbit

NASA Technical Reports Server (NTRS)

Maran, S. P.; Heinsheimer, T. F.; Stocker, T. L.; Anand, S. P. S.; Chapman, R. D.; Hobbs, R. W.; Michalitsanos, A. G.; Wright, F. H.; Kipp, S. L.

1976-01-01

A program is discussed which involved monitoring the photometric activity of 18 bright variable IR stars at 2.7 microns with satellite- and rocket-borne instrumentation in the period from 1971 to 1975. The stellar sample includes 3 Lb variables, 8 semiregular variables, 5 Mira-type variables, and 2 previously unknown and unclassified IR variables. Detailed light curves of many of these stars were determined for intervals of 3 yr or more; spectra from 2.7 to 20 microns were constructed for nine of them using data obtained entirely with instruments above the atmosphere. Photometric IR light curves and other data are presented for SW Virginis, R Aquilae, S Scuti, IRC 00265, RT Hydrae, S Orionis, S Canis Minoris, Omicron Ceti, and R Leonis. Several hypotheses concerning the interpretation of the IR data are examined.

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

Pott, Jorg-Uwe; Perrin, Marshall D.; Furlan, Elise

With the Keck Interferometer, we have studied at 2 {mu}m the innermost regions of several nearby, young, dust-depleted 'transitional' disks. Our observations target five of the six clearest cases of transitional disks in the Taurus/Auriga star-forming region (DM Tau, GM Aur, LkCa 15, UX Tau A, and RY Tau) to explore the possibility that the depletion of optically thick dust from the inner disks is caused by stellar companions rather than the more typical planet-formation hypothesis. At the 99.7% confidence level, the observed visibilities exclude binaries with flux ratios of at least 0.05 and separations ranging from 2.5 to 30more » mas (0.35-4 AU) over {approx}>94% of the area covered by our measurements. All targets but DM Tau show near-infrared (NIR) excess in their spectral energy distribution (SED) higher than our companion flux ratio detection limits. While a companion has previously been detected in the candidate transitional disk system CoKu Tau/4, we can exclude similar mass companions as the typical origin for the clearing of inner dust in transitional disks and of the NIR excess emission. Unlike CoKu Tau/4, all our targets show some evidence of accretion. We find that all but one of the targets are clearly spatially resolved, and UX Tau A is marginally resolved. Our data are consistent with hot material on small scales (0.1 AU) inside of and separated from the cooler outer disk, consistent with the recent SED modeling. These observations support the notion that some transitional disks have radial gaps in their optically thick material, which could be an indication for planet formation in the habitable zone ({approx} a few AU) of a protoplanetary disk.« less

Merging Imagery and Models for River Current Prediction

DTIC Science & Technology

2011-01-01

synthetically generated bathymetry. Measured Batbymel ry Synthetic Batbymel rj Mooring Mean Difference (nn/s) Correlation Mian Difference (cm s...8217orrelal ion Al Mi 0.90 27 077 A 2 17 0.86 21 n 36 Bl 17 0.87 21 B2 17 0.89 2 1 DJO 133 li , 0.87 23 0.87 is that mean differences between tlie

Thermal Transport in Diamond Films for Electronics Thermal Management

DTIC Science & Technology

2018-03-01

AFRL-RY-WP-TR-2017-0219 THERMAL TRANSPORT IN DIAMOND FILMS FOR ELECTRONICS THERMAL MANAGEMENT Samuel Graham Georgia Institute of Technology MARCH...general public, including foreign nationals. Copies may be obtained from the Defense Technical Information Center (DTIC) (http://www.dtic.mil...Signature// JOHN D. BLEVINS, Program Manager ROSS W. DETTMER, Chief Devices for Sensing Branch Devices for Sensing Branch Aerospace Components

Vehicle Test Facilities at Aberdeen Proving Ground

DTIC Science & Technology

1981-07-06

warehouse and rough terrain forklifts. Two 5-ton-capacity manual chain hoists at the rear of the table regulate its slope from 0 to 40 percent. The overall...Capacity at 24-Inch Load Center. 5. TOP/ HTP 2-2-608, Braking, Wheeled Vehicles, 15 Jav.&ry 1971. 6. TOP 2-2-603, Vehicle Fuel Consumption, 1 November 1977. A-1 r -. ’,’

77 FR 12909 - Eastern Maine Railway Company-Acquisition and Operation Exemption-Montreal, Maine & Atlantic...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... Canadian Natl. Ry.--Trackage Rights Exemption--Bangor and Aroostook R.R. and Van Buren Bridge Co., FD 34014... Buren Bridge Co., FD 34015 (STB served Mar. 21, 2001). The transaction is expected to be consummated on... transaction will not result in the creation of a Class II or Class I rail carrier. Because EMR's projected...

Human Factors Engineering. Part 1. Test Procedures

DTIC Science & Technology

1990-05-15

b, given to offset mem ’,ry effects, and all participants should begin the test at the same i~erneral level of familiarity with the item. The HFE...Pop ohp l _________________________ CL PUWH p@e flpSI _____________ o AwjiqjIsA poonpojj x x x x x x P L)56MIS P*otnpo8 LIJ U Alijoixec3 poonpoW x x x

Computer Graphics Research Laboratory

DTIC Science & Technology

1994-01-31

loken language (words and contextually appropriate intonation marking topic and focus), fac %. iove- ments (lip shapes, emotions , gaze direction, head...content of speech (scrunching one’s lose when talking about something unpleasant), emotion (wrinkling one’s eyebrows with wov ry), personality...ng at the other person to see how she follows), look for information, express emotion (lookii , downward in case of sadness), or influence another

Computer-Aided Detection of Rapid, Overt, Airborne, Reconnaissance Data with the Capability of Removing Oceanic Noises

DTIC Science & Technology

2013-12-01

dl--NA’u•-.llw l"\\l;t.l"t, "’’"~r~ll•t• ·•~r•d "’lcottt~ry oaf"!’@ 11\\•ol\\dorwu"’ Mtb! .ctv• titA Mourtd 1Nl..en.ce l’llntell•eR ~ltl4.nftUt!rlc

One to Grow On/Fox Taming and Teaching

ERIC Educational Resources Information Center

Tomlinson, Carol Ann

2016-01-01

In this article, Carol Ann Tomlinson, an English teacher of 20 years is asked from time to time, what her favorite book is. Her response, Antoine de Saint-Exupéry's "The Little Prince" (Harcourt, Brace & World, 1943), the story of a little boy who is trying to find his way in a confusing world. At one particularly dismaying moment in…

Grounding Undns

DTIC Science & Technology

2012-01-01

PROJECT NUMBER BYU1 5e. TASK NUMBER MA 5f. WORK UNIT NUMBER RY 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) University of Maryland Office of...Research Administration & Advancement College Park MD 20742-5100 8. PERFORMING ORGANIZATION REPORT NUMBER N/A 9. SPONSORING...Armed with these metrics, the Undns ruleset is better revised, vestigial rules removed or demoted for maintenance, and redundant locations distinguished

75 FR 21146 - Union Pacific Railroad Company-Trackage Rights Exemption-BNSF Railway Company

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

...--Burlington N., Inc., 354 I.C.C. 605 (1978), as modified in Mendocino Coast Ry.--Lease and Operate--Cal. W. R... pleading must be served on Mack H. Shumate, Jr., Senior General Attorney, Union Pacific Railroad Company... Web site at `` http://www.stb.dot.gov .'' Decided: April 19, 2010. By the Board, Rachel D. Campbell...

Vitamin D Levels and Related Genetic Polymorphisms, Sun Exposure, Skin Color, and Risk of Aggressive Prostate Cancer

DTIC Science & Technology

2012-07-01

for our specific aims. 15. SUBJECT TERMS vitamin D deficiency, prostate cancer, health disparities, African American 16. SECURITY CLASSIFICATION OF...ler.reb (If - 0.43 wen aJECia6!d with ~ iota re.icleaa~ in tbe lropi.:. (~- 5.60, p- 114), &t:.ry vibnoio D iobsb @- 0.01, p- ,OJ); IIILd supplmu1Ji