Transcriptomic-wide discovery of direct and indirect HuR RNA targets in activated CD4+ T cells

Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs) and microRNAs (miRNAs). RNA immunoprecipitation (RIP) methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1) and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads) that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads) to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms

Reversing non-local transport through a superconductor by electromagnetic excitations

Superconductors connected to normal metallic electrodes at the nanoscale provide a potential source of non-locally entangled electron pairs. Such states would arise from Cooper pairs splitting into two electrons with opposite spins tunnelling into different leads. In an actual system the detection of these processes is hindered by the elastic transmission of individual electrons between the leads, yielding an opposite contribution to the non-local conductance. Here we show that electromagnetic excitations on the superconductor can play an important role in altering the balance between these two processes, leading to a dominance of one upon the other depending on the spatial symmetry of these excitations. These findings allow to understand some intriguing recent experimental results and open the possibility to control non-local transport through a superconductor by an appropriate design of the experimental geometry.Comment: 6 pages, 3 figure

Final-state interaction phase difference in J/ψ→ρηJ/\psi\to\rho\eta and ωη\omega\eta decays

It is shown that the study of the $\omega-\rho^0$ interference pattern in the $J/\psi\to (\rho^0+\omega)\eta\to\pi^+\pi^-\eta$ decay provides the evidence for the large (nearly $90^\circ$) relative phase between the one-photon and the three-gluon decay amplitudes.Comment: 5 pages, revtex, \tightenlines, a version published in Phys. Rev. D 61, 117504 (2000

Overexpression of the RNA-binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis [abstract]

Breast cancer is the second most common cancer in women and causes the death of 519,000 people worldwide. Many cancer genes are posttranscriptionally regulated by RNA-binding proteins (RBPs) and microRNAs. The RBP HuR binds to the AU-rich (ARE) regions of labile mRNAs, such as proto-oncogenes, stabilizing their mRNA and facilitating their translation into protein. HuR has been described to control genes in multiple areas of the acquired capabilities model of cancer and has been hypothesized to be a tumor maintenance gene, allowing for cancers to proliferate once they are established. We investigated the role of HuR in aggressive and difficult to treat triple-negative breast cancer

Analysis of the nature of the ϕ→γπη\phi\to\gamma\pi\eta and ϕ→γπ0π0\phi\to\gamma\pi^0\pi^0 decays

We study interference patterns in the $\phi\to(\gamma a_0+\pi^0\rho)\to\gamma\pi\eta$ and $\phi\to(\gamma f_0+\pi^0\rho)\to\gamma \pi^0\pi^0$ reactions. Taking into account the interference, we fit the experimental data and show that the background reaction does not distort the $\pi^0\eta$ spectrum in the decay $\phi\to\gamma\pi\eta$ everywhere over the energy region and does not distort the $\pi^0\pi^0$ spectrum in the decay $\phi\to\gamma\pi^0\pi^0$ in the wide region of the $\pi^0\pi^0$ system invariant mass, $m_{\pi\pi}>670$ MeV, or when the photon energy is less than 300 MeV. We discuss the details of the scalar meson production in the radiative decays and note that there are reasonable arguments in favor of the one-loop mechanism $\phi\to K^+K^-\to\gamma a_0$ and $\phi\to K^+K^-\to\gamma f_0$. We discuss also distinctions between the four-quark, molecular, and two-quark models and argue that the Novosibirsk data give evidence in favor of the four-quark nature of the scalar $a_0(980)$ and $f_0(980)$ mesons.Comment: 15 pages, 7 figures, title is changed, a few clarifying remarks are added, accepted for publication in Physical Review

Effects of habitat and livestock on nest productivity of the Asian houbara Chlamydotis macqueenii in Bukhara Province, Uzbekistan

To inform population support measures for the unsustainably hunted Asian houbara Chlamydotis macqueenii (IUCN Vulnerable) we examined potential habitat and land-use effects on nest productivity in the Kyzylkum Desert, Uzbekistan. We monitored 177 nests across different semi-arid shrub assemblages (clay-sand and salinity gradients) and a range of livestock densities (0–80 km-2). Nest success (mean 51.4%, 95% CI 42.4–60.4%) was similar across four years; predation caused 85% of those failures for which the cause was known, and only three nests were trampled by livestock. Nesting begins within a few weeks of arrival when food appears scarce, but later nests were more likely to fail owing to the emergence of a key predator, suggesting foraging conditions on wintering and passage sites may be important for nest productivity. Nest success was similar across three shrub assemblages and was unrelated to landscape rugosity, shrub frequency or livestock density, but was greater with taller mean shrub height (range 13–67 cm) within 50 m. Clutch size (mean = 3.2 eggs) and per-egg hatchability in successful nests (87.5%) did not differ with laying date, shrub assemblage or livestock density. We therefore found no evidence that livestock density reduced nest productivity across the range examined, while differing shrub assemblages appeared to offer similar habitat quality. Asian houbara appear well-adapted to a range of semi-desert habitats and tolerate moderate disturbance by pastoralism. No obvious in situ mitigation measures arise from these findings, leaving regulation and control as the key requirement to render hunting sustainable

The interference in the reaction e+e−→γπ+π−e^+e^-\to\gamma\pi^+\pi^- and the search for the decay ϕ→γf0→γπ+π−\phi\to\gamma f_0\to\gamma\pi^+\pi^-

We describe the interference between amplitudes $e^+e^- \to \rho \to \gamma\pi^+\pi^-$ and $e^+e^- \to \phi \to \gamma f_0 \to \gamma\pi^+\pi^-$, where $f_0$ meson is considered in the frameworks of the four-quark model and the model of the scalar $K\bar K$ molecule. The general expressions for the differential cross section with the radiative corrections and two angle cuts are given. The interference patterns are obtained in the spectrum of the differential cross section by the energy of the photon and in the full cross section by the energy of the beams.Comment: 21 pages, revtex, 8 ps files of figure