Identification of antiviral roles for the exon-junction complex and nonsense-mediated decay in flaviviral infection.

West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (APMS) study to identify 259 WNV-interacting human proteins. RNA interference screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral and the EJC protein RBM8A directly binds WNV RNA. To counteract this, flavivirus infection inhibits NMD and the capsid-PYM1 interaction interferes with EJC protein function and localization. Depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC

Non-Standard Interactions: Atmospheric versus Neutrino Factory Experiments

We consider the potential of a generic neutrino factory (NUFACT) in probing non-standard neutrino-matter interactions (NSI). We find that the sensitivity to flavour-changing (FC) NSI can be substantially improved with respect to present atmospheric neutrino data, especially at energies higher than approximately 50 GeV, where the effect of the tau mass is small. For example, a 100 GeV NUFACT can probe FC neutrino interactions at the level of few $|\epsilon| < {few} \times 10^{-4}$ at 99 % C.L.Comment: 20 pages, 4 figures, references added, version to appear in Phys. Lett.

Role of the HSP90-Associated Cochaperone p23 in Enhancing Activity of the Androgen Receptor and Significance for Prostate Cancer

Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been re-ported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (en-hancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer. © 2012 by The Endocrine Society

When Does Construction Enhance Product Value? Investigating the Combined Effects of Object Assembly and Ownership on Valuation

Recent findings have shown that even without the ability to customize a product, individuals pay more for goods that they assembled. In this paper we examine which components of this creation process account for this increase in valuation, and whether it operates equally for owners and non-owners of the self-assembled object. Based on the self-extension theory of ownership, we propose a psychological mechanism by which the assembly process strengthens the self-object association. In three experiments, we find that – although witnessing the assembly process or assembling a similar product can increase participants’ evaluation of, and attachment to, a product that they own – a greater and more consistent increase in valuation and attachment arises when owners assemble their product themselves. Seemingly, merely learning about the assembly process plays only a small role in enhancing value; for substantial increases in value, one must actually assemble the product oneself. Contrary to the previous findings on the effects of labour on willingness to pay, we find little effect of product assembly among non-owners of the product. We suggest that self-assembly encourages objects to be incorporated into the self, but that this occurs most effectively when one owns the product. Keywords: product assembly,This is the author accepted manuscript. The final version is available from Wiley via https://doi.org/10.1002/bdm.193

Confusing non-standard neutrino interactions with oscillations at a neutrino factory

Most neutrino mass theories contain non-standard interactions (NSI) of neutrinos which can be either non-universal (NU) or flavor-changing (FC). We study the impact of such interactions on the determination of neutrino mixing parameters at a neutrino factory using the so-called ``golden channels'' \pnu{e}\to\pnu{\mu} for the measurement of \theta_{13}. We show that a certain combination of FC interactions in neutrino source and earth matter can give exactly the same signal as oscillations arising due to \theta_{13}. This implies that information about \theta_{13} can only be obtained if bounds on NSI are available. Taking into account the existing bounds on FC interactions, this leads to a drastic loss in sensitivity in \theta_{13}, at least two orders of magnitude. A near detector at a neutrino factory offers the possibility to obtain stringent bounds on some NSI parameters. Such near site detector constitutes an essential ingredient of a neutrino factory and a necessary step towards the determination of \theta_{13} and subsequent study of leptonic CP violation.Comment: 23 pages, 5 figures, improved version, accepted for publication in Phs. Rev. D, references adde

tRNA biology in the omics era: Stress signalling dynamics and cancer progression.

Recent years have seen a burst in the number of studies investigating tRNA biology. With the transition from a gene-centred to a genome-centred perspective, tRNAs and other RNA polymerase III transcripts surfaced as active regulators of normal cell physiology and disease. Novel strategies removing some of the hurdles that prevent quantitative tRNA profiling revealed that the differential exploitation of the tRNA pool critically affects the ability of the cell to balance protein homeostasis during normal and stress conditions. Furthermore, growing evidence indicates that the adaptation of tRNA synthesis to cellular dynamics can influence translation and mRNA stability to drive carcinogenesis and other pathological disorders. This review explores the contribution given by genomics, transcriptomics and epitranscriptomics to the discovery of emerging tRNA functions, and gives insights into some of the technical challenges that still limit our understanding of the RNA polymerase III transcriptional machinery

Corporate governance and cash holdings in MENA: evidence from internal and external governance practices

This paper explores the impact of internal and external corporate governance practices on the decision to hold cash in MENA countries. Using 430 non-financial firms in the MENA region for the period from 2000 to 2009, we find that both types of governance practices are important. We report a negative relationship between board size and cash holdings, evidence that firms hold less cash to reduce agency conflicts. Also, we detect that external governance activities are important in cash holding decisions, since we report that firms belonging to countries with international standards of securities law and bank supervision hold less cash. For our sub-sample of 85 firms, we report evidence that institutional owners are seen to be self-opportunistic and that they aim to maximize their own private benefit

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