Recovery of the X-Ray Transient QX Nor (=X1608-52) in Outburst and Quiescence

We present optical and near-IR observations of QX Nor, the counterpart to the recurrent soft X-ray transient X1608-52, after its reappearance following the X-ray outburst in February 1996. The object has been seen only once before, during an X-ray outburst in 1977. Data from 3-5 months after the outburst show the counterpart at a mean magnitude of R=20.2 and variable on timescales of days. A comparison with identical observations in 1995 implies that the object has brightened by at least 1.8 mag in R following the X-ray outburst. We also detected QX Nor in the IR in both quiescence and outburst. A faint source is visible in the J but not the R band in May 1995. These first observations in the quiescent state yield magnitudes and colors consistent with optical emission from a low mass companion in the binary system, as is true in other soft X-ray transients.Comment: 10 pages including 4 figures and 2 tables; Uses AASTeX 4.0; Accepted for publication in The Astrophysical Journal, Volume 485, August 20, 199

Doxorubicin-induced DNA Damage Causes Extensive Ubiquitination of Ribosomal Proteins Associated with a Decrease in Protein Translation

Protein posttranslational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signaling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9,400 ubiquitin sites and found that the relative abundance of similar to 10% of these sites was altered in response to DNA double-strand breaks. Interestingly, a large proportion of ribosomal proteins, including those from the 40S as well as the 60S subunit, were ubiquitinated in response to DNA damage. In parallel, we discovered that DNA damage leads to the inhibition of ribosome function. Taken together, these data uncover the ribosome as a major target of the DNA damage response.This work is funded by a TOP-GO grant from the Netherlands Organization for Scientific Research (NWO ZonMW 912100651 to R.H.M., S.M., and V.A.H.). I.G.S. was supported with a postdoctoral fellowship from the Basque Country Government (Spain). We thank Christian Frese and Teck Yew Low for fruitful discussions. We also thank Teck Yew Low for submitting the raw files and annotated spectra to PRIDE. We thank Fabricio Loayza-Puch for his technical help with the sucrose gradients

New Results for Two Optically Faint Low Mass X-Ray Binary Systems

We present optical photometry of the low mass X-ray binary systems GX 349+2 and Ser X-1. Extensive VRI photometry of the faint optical counterpart (V=18.4) to GX 349+2 reveals a period of 22.5 +/- 0.1 h and half-amplitude 0.2 mag. This result confirms and extends our previously reported 22 h period. No color change is detected over the orbit, although the limits are modest. We also report the discovery of two new variable stars in the field of GX 349+2, including a probable W UMa system. Ser X-1 is one of the most intense persistent X-ray burst sources known. It is also one of only three burst systems for which simultaneous optical and X-ray bursts have been observed. The faint blue optical counterpart MM Ser (B~19.2) has long been known to have a companion 2.1" distant. Our images indicate that MM Ser is itself a further superposition of two stars, separated by only 1". At the very least, the ratio of inferred burst to quiescent optical flux is affected by the discovery of this additional component. In the worst case, the wrong object may have previously been assumed as the optical counterpart.Comment: 16 pages including 10 figures and 3 tables; Uses AASTeX 4.0; Accepted for publication in The Astrophysical Journal, Volume 490, November 20, 199

Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7

The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate–enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes. In this study, we demonstrate that the guanosine triphosphatase Rab7 contributes to this recruitment. The Vps26/29/35 trimer specifically binds to Rab7–guanosine triphosphate (GTP) and localizes to Rab7-containing endosomal domains. Interference with Rab7 function causes dissociation of the Vps26/29/35 trimer but not the SNX dimer from membranes. This blocks retrieval of mannose 6-phosphate receptors to the TGN and impairs cathepsin D sorting. Rab5-GTP does not bind to the Vps26/29/35 trimer, but perturbation of Rab5 function causes dissociation of both the SNX and Vps26/29/35 components from membranes through inhibition of a pathway involving phosphatidylinositol 3-kinase. These findings demonstrate that Rab5 and Rab7 act in concert to regulate retromer recruitment to endosomes

Rapid Analyses of Proteomes and Interactomes Using an Integrated Solid-Phase Extraction–Liquid Chromatography–MS/MS System

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The Formation of Low-Mass Transient X-Ray Binaries

We consider constraints on the formation of low-mass X-ray binaries containing neutron stars (NLMXBs) arising from the presence of soft X-ray transients among these systems. We show that in short-period systems driven by angular momentum loss these constraints require the secondary at the beginning of mass transfer to have a mass > 1.2 M_sun, and to be significantly nuclear-evolved. As a consequence a comparatively large fraction of such systems appear as soft X-ray transients even at short periods, as observed. Moreover the large initial secondary masses account for the rarity of NLMXBs at periods less than 3 hr. In contrast, NLMXB populations forming with large kick velocities would not have these properties, suggesting that the kick velocity is generally small compared to the pre-SN orbital velocity in a large fraction of systems. We derive constraints on progenitor system parameters and on the strength of magnetic braking.Comment: Accepted for publication in ApJ, 19 pages, 4 figure

Enhancing Europe’s global power: a scenario exercise with eight proposals

In the present context of intensifying competition between the major trading economies and potentially game-changing technological developments, the European Union is generally seen as the weaker party. Lacking the ‘hard power’ derived from military capabilities, it has laid claim to a ‘soft power’ of normative influence externally, yet even that is only partially utilised. Nor has Europe been able to exercise the power to coerce – ‘sharp power’ – commensurate with its economic weight as a trading bloc equivalent in size and reach to the US or China, its most prominent global competitors. How can Europe strengthen its position, and in what fields? Through a scenario exercise, we develop eight policy proposals aimed at countering Europe´s vulnerabilities and enabling it to assert its sharp and soft power more effectively. Specifically, we consider the feasibility, means and scope for their realisation. Together, they provide a transformative agenda for the EU’s position in the world

The Leukemia-Associated Mllt10/Af10-Dot1l Are Tcf4/β-Catenin Coactivators Essential for Intestinal Homeostasis

The leukemia-associated Mllt10/Af10 and its partner the histone methyltransferase Dot1l are identified as Tcf4/β-catenin co-activators and shown to be essential for Wnt-driven endogenous gene expression, intestinal development and homeostasis

Perturbation of the yeast N-acetyltransferase NatB induces elevation of protein phosphorylation levels

<p>Abstract</p> <p>Background</p> <p>The addition of an acetyl group to protein N-termini is a widespread co-translational modification. NatB is one of the main N-acetyltransferases that targets a subset of proteins possessing an N-terminal methionine, but so far only a handful of substrates have been reported. Using a yeast <it>nat3Δ </it>strain, deficient for the catalytic subunit of NatB, we employed a quantitative proteomics strategy to identify NatB substrates and to characterize downstream effects in <it>nat3Δ</it>.</p> <p>Results</p> <p>Comparing by proteomics WT and <it>nat3Δ </it>strains, using metabolic ¹⁵N isotope labeling, we confidently identified 59 NatB substrates, out of a total of 756 detected acetylated protein N-termini. We acquired in-depth proteome wide measurements of expression levels of about 2580 proteins. Most remarkably, NatB deletion led to a very significant change in protein phosphorylation.</p> <p>Conclusions</p> <p>Protein expression levels change only marginally in between WT and <it>nat3Δ</it>. A comparison of the detected NatB substrates with their orthologous revealed remarkably little conservation throughout the phylogenetic tree. We further present evidence of post-translational N-acetylation on protein variants at non-annotated N-termini. Moreover, analysis of downstream effects in <it>nat3Δ </it>revealed elevated protein phosphorylation levels whereby the kinase Snf1p is likely a key element in this process.</p