Reinvestigation of aminoacyl-TRNA synthetase core complex by affinity purification-mass spectrometry reveals TARSL2 as a potential member of the complex

10.1371/journal.pone.0081734PLoS ONE812-POLN

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Guidelines for the use and interpretation of assays for monitoring autophagy (2nd edition)

In 2008 we published the first set of guidelines for standardiz- ing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new tech- nologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in differ- ent organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes..

Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts

Wavelets are a powerful tool for signal and image denoising. Most of the denoising applications in different fields were based on the thresholding of the discrete wavelet transform (DWT) coefficients. Nevertheless, DWT transform is not a time or shift invariant transform and results depend on the selected shift. Improvements on the denoising performance can be obtained using the stationary wavelet transform (SWT) (also called shift-invariant or undecimated wavelet transform). Denoising using SWT has previously shown a robust and usually better performance than denoising using DWT but with a higher computational cost. In this paper, wavelet shrinkage schemes are applied for reducing noise in synthetic and experimental non-destructive evaluation ultrasonic A-scans, using DWT and a cycle-spinning implementation of SWT. A new denoising procedure, which we call random partial cycle spinning (RPCS), is presented. It is based on a cycle-spinning over a limited number of shifts that are selected in a random way. Wavelet denoising based on DWT, SWT and RPCS have been applied to the same sets of ultrasonic A-scans and their performances in terms of SNR are compared. In all cases three well known threshold selection rules (Universal, Minimax and Sure), with decomposition level dependent selection, have been used. It is shown that the new procedure provides a good robust denoising performance, without the DWT fluctuating performance, and close to SWT but with a much lower computational cost.This work was partially supported by Spanish MCI Project DPI2011-22438San Emeterio Prieto, JL.; Rodríguez-Hernández, MA. (2015). Wavelet Cycle Spinning Denoising of NDE Ultrasonic Signals Using a Random Selection of Shifts. Journal of Nondestructive Evaluation. 34(1):1-8. https://doi.org/10.1007/s10921-014-0270-8S18341Galloway, R.L., McDermott, B.A., Thurstone, F.L.: A frequency diversity process for speckle reduction in real-time ultrasonic images. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 35, 45–49 (1988)Newhouse, V.L., Bilgutay, N.M., Saniie, J., Furgason, E.S.: Flaw-to-grain echo enhancement by split spectrum processing. Ultrasonics 20, 59–68 (1982)Karpur, P., Canelones, O.J.: Split spectrum processing: a new filtering approach for improved signal-to-noise ratio enhancement of ultrasonic signals. Ultrasonics 30, 351–357 (1992)Donoho, D.L., Johnstone, I.M.: Ideal spatial adaptation by wavelet shrinkage. Biometrika 81, 425–455 (1994)Donoho, D.L., Johnstone, I.M., Kerkyacharian, G., Picard, D.: Wavelet shrinkage: asymptotia? J. R Stat. Soc. Ser. B 57, 301–369 (1995)Donoho, D.L., Johnstone, I.M.: Adapting to unknown smoothness via wavelet shrinkage. J. Am. Stat. Assoc. 90, 1200–1224 (1995)Johnstone, I.M., Silverman, B.W.: Wavelet threshold estimators for data with correlated noise. J. R Stat. Soc. 59, 319–351 (1997)Jansen, M.: Noise Reduction by Wavelet Thresholding. Lecture Notes in Statistics 161. Springer, New York (2001). doi: 10.1007/978-1-4613-0145-5Nason, G.P., Silverman, B.W.:The stationary wavelet transform and some statistical applications. In: Antoniadis, A., Oppenheim, G. (eds.) Wavelets and Statistics. Lecture Notes in Statistics, Vol. 103, pp 281–299. Springer, New York (1995)Lang, M., Guo, H., Odegard, J.E., Burrus, C.S.: Noise reduction using an undecimated discrete wavelet transform. IEEE Signal Proc. Lett. 3, 10–12 (1996)Coifman, R.R., Donoho, D.L.: Translation-invariant de-noising. In: Antoniadis, A., Oppenheim, G. (eds.) Wavelets and Statistics. Lecture Notes in Statistics, vol. 103, pp 125–150, Springer, New York (1995) .Abbate, A., Koay, J., Frankel, J., Schroeder, S.C., Das, P.: Signal detection and noise suppression using a wavelet transform signal processor: application to ultrasonic flaw detection. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 44, 14–26 (1997)Lázaro, J.C., San Emeterio, J.L., Ramos, A., Fernandez, J.L.: Influence of thresholding procedures in ultrasonic grain noise reduction using wavelets. Ultrasonics 40, 263–267 (2002)Matz, V., Smid, R., Starman, S., Kreidl, M.: Signal-to-noise ratio enhancement based on wavelet filtering in ultrasonic testing. Ultrasonics 49, 752–759 (2009)Kubinyi, M., Kreibich, O., Neuzil, J., Smid, R.: EMAT noise suppression using information fusion in stationary wavelet packets. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 1027–1036 (2011)Shi, G.M., Chen, X.Y., Song, X.X., Qui, F., Ding, A.L.: Signal matching wavelet for ultrasonic flaw detection in high background noise. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 776–787 (2011)Song, S.P., Que, P.W.: Wavelet based noise suppression technique and its application to ultrasonic flaw detection. Ultrasonics 44, 188–193 (2006)Rodriguez, M.A., San Emeterio, J.L., Lázaro, J.C., Ramos, A.: Ultrasonic flaw detection in NDE of highly scattering materials using wavelet and Wigner-Ville transform processing. Ultrasonics 42, 847–851 (2004)Zhang, G.M., Zhang, S.Y., Wang, Y.W.: Application of adaptive time-frequency decomposition in ultrasonic NDE of highly-scattering materials. Ultrasonics 38, 961–964 (2000)Drai, R., Khelil, M., Benchaala, A.: Time frequency and wavelet transform applied to selected problems in ultrasonics NDE. NDT & E Int. 35, 567–572 (2002)Pardo, E., San Emeterio, J.L.: Noise reduction in ultrasonic NDT using undecimated wavelet transforms. Ultrasonics 44, e1063–e1067 (2006)Kechida, A., Drai, R., Guessoum, A.: Texture analysis for flaw detection in ultrasonic images. J. Nondestruct. Eval. 31, 108–116 (2012). doi: 10.1007/s10921-011-0126-4Rucka, M., Wilde, K.: Experimental study on ultrasonic monitoring of splitting failure in reinforced concrete. J. Nondestruct. Eval. 32, 372–383 (2013). doi: 10.1007/s10921-013-0191-yHosseini, S.M.H., Duczek, S., Gabbert, U.: Damage localization in plates using mode conversion characteristics of ultrasonic guided waves. J. Nondestruct. Eval. 33, 152–165 (2014). doi: 10.1007/s10921-013-0211-yMohammed, M.S., Ki-Seong, K.: Shift-invariant wavelet packet for signal de-noising in ultrasonic testing. Insight 54, 366–370 (2012)San Emeterio, J.L., Rodriguez-Hernandez, M.A.: Wavelet denoising of ultrasonic A-scans by random partial cycle spinning. In: Proceedings of the 2012 IEEE International Ultrasonics Symposium. pp 455–458.Mallat, S.G.: A theory of multiresolution signal decomposition: the wavelet representation. IEEE Trans. Pattern Anal. Mach. Intell. 11, 674–693 (1989)Shensa, M.J.: The discrete wavelet transform: wedding the à trous and Mallat algorithms. IEEE Trans. Signal Process. 40, 2464–2482 (1992). doi: 10.1109/78.157290Beylkin, G., Coifman, R., Rokhlin, V.: Fast wavelet transforms and numerical algorithms. Commun. Pure Appl. Math. 44, 141–183 (1991)Daubechies, I.: Ten Lectures on Wavelets. SIAM, Philadelphia (1992)Romijn, R.L., Thijssen, J.M., Vanbeuningen, G.W.J.: Estimation of scatterer size from backscattered ultrasound: a simulation study. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 36, 593–606 (1989)Gustafsson, M.G., Stepinski, T.: Studies of split spectrum processing, optimal detection, and maximum likehood amplitude estimation using a simple clutter model. Ultrasonics 35, 31–53 (1997

Sex-specific genetic effects influence variation in body composition

Aims/hypothesis: Despite well-known sex differences in body composition it is not known whether sex-specific genetic or environmental effects contribute to these differences. Methods: We assessed body composition in 2,506 individuals, from a young Dutch genetic isolate participating in the Erasmus Rucphen Family study, by dual-energy X-ray absorptiometry and anthropometry. We used variance decomposition procedures to partition variation of body composition into genetic and environmental components common to both sexes and to men and women separately and calculated the correlation between genetic components in men and women. Results: After accounting for age

Molecular Basis of Ligand Dissociation in β-Adrenergic Receptors

The important and diverse biological functions of β-adrenergic receptors (βARs) have promoted the search for compounds to stimulate or inhibit their activity. In this regard, unraveling the molecular basis of ligand binding/unbinding events is essential to understand the pharmacological properties of these G protein-coupled receptors. In this study, we use the steered molecular dynamics simulation method to describe, in atomic detail, the unbinding process of two inverse agonists, which have been recently co-crystallized with β1 and β2ARs subtypes, along four different channels. Our results indicate that this type of compounds likely accesses the orthosteric binding site of βARs from the extracellular water environment. Importantly, reconstruction of forces and energies from the simulations of the dissociation process suggests, for the first time, the presence of secondary binding sites located in the extracellular loops 2 and 3 and transmembrane helix 7, where ligands are transiently retained by electrostatic and Van der Waals interactions. Comparison of the residues that form these new transient allosteric binding sites in both βARs subtypes reveals the importance of non-conserved electrostatic interactions as well as conserved aromatic contacts in the early steps of the binding process

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres