The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer

RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression of the protein in hepatocellular and lung cancers is correlated with adverse prognosis. LARP1 associates with an mRNA interactome that is enriched for oncogenic transcripts. Here we explore the role of LARP1 in epithelial ovarian cancer, a disease characterized by the rapid acquisition of resistance to chemotherapy through the induction of pro-survival signalling. We show, using ovarian cell lines and xenografts, that LARP1 is required for cancer cell survival and chemotherapy resistance. LARP1 promotes tumour formation in vivo and maintains cancer stem cell-like populations. Using transcriptomic analysis following LARP1 knockdown, cross-referenced against the LARP1 interactome, we identify BCL2 and BIK as LARP1 mRNA targets. We demonstrate that, through an interaction with the 3 untranslated regions (3 UTRs) of BCL2 and BIK, LARP1 stabilizes BCL2 but destabilizes BIK with the net effect of resisting apoptosis. Together, our data indicate that by differentially regulating the stability of a selection of mRNAs, LARP1 promotes ovarian cancer progression and chemotherapy resistance

A spectroscopic analysis of a sample of narrow-line Seyfert 1 galaxies selected from the Sloan Digital Sky Survey

We revisited the spectroscopic characteristics of narrow-line Seyfert 1 galaxies (NLS1s) by analysing a homogeneous sample of 296 NLS1s at redshift between 0.028 and 0.345, extracted from the Sloan Digital Sky Survey (SDSS-DR7) public archive. We confirm that NLS1s are mostly characterized by Balmer lines with Lorentzian profiles, lower black hole masses and higher Eddington ratios than classic broad-line Seyfert 1 (BLS1s), but they also appear to be active galactic nuclei (AGNs) contiguous with BLS1s and sharing with them common properties. Strong Fe II emission does not seem to be a distinctive property of NLS1s, as low values of Fe II/H$\beta$ are equally observed in these AGNs. Our data indicate that Fe II and Ca II kinematics are consistent with the one of H$\beta$. On the contrary, O I $\lambda$8446 seems to be systematically narrower and it is likely emitted by gas of the broad-line region more distant from the ionizing source and showing different physical properties. Finally, almost all NLS1s of our sample show radial motions of the narrow-line region highly-ionised gas. The mechanism responsible for this effect is not yet clear, but there are hints that very fast outflows require high continuum luminosities (> $10^{44}$ erg/s) or high Eddington ratios (log(L$_{\rm bol}$/L$_{\rm Edd}$) > -0.1).Comment: 27 pages, 31 figures, 4 tables, accepted for publication in MNRA

High resolution spectroscopy of the extended narrow-line region of IC 5063 and NGC 7212

We studied the properties of the gas of the extended narrow line region (ENLR) of two Seyfert 2 galaxies: IC 5063 and NGC 7212. We analysed high resolution spectra to investigate how the main properties of this region depend on the gas velocity. We divided the emission lines in velocity bins and we calculated several line ratios. Diagnostic diagrams and SUMA composite models (photo-ionization + shocks), show that in both galaxies there might be evidence of shocks significantly contributing in the gas ionization at high |V|, even though photo-ionization from the active nucleus remains the main ionization mechanism. In IC 5063 the ionization parameter depends on V and its trend might be explained assuming an hollow bi-conical shape for the ENLR, with one of the edges aligned with the galaxy disk. On the other hand, NGC 7212 does not show any kind of dependence. The models show that solar O/H relative abundances reproduce the observed spectra in all the analysed regions. They also revealed an high fragmentation of the gas clouds, suggesting that the complex kinematics observed in these two objects might be caused by interaction between the ISM and high velocity components, such as jets.Comment: 29 pages, 32 figures, accepted for publication in MNRA

[O III] line properties in two samples of radio-emitting narrow-line Seyfert 1 galaxies

The [O III] $\lambda\lambda$ 4959,5007 lines are a useful proxy to test the kinematic of the narrow-line region (NLR) in active galactic nuclei (AGN). In AGN, and particularly in narrow-line Seyfert 1 galaxies (NLS1s) these lines often show few peculiar features, such as blue wings, often interpreted as outflowing component, and a shift $-$ typically toward lower wavelengths $-$ of the whole spectroscopic feature in some exceptional sources, the so-called blue outliers, which are often associated to strong winds. We investigated the incidence of these peculiarities in two samples of radio-emitting NLS1s, one radio-loud and one radio-quiet. We also studied a few correlations between the observational properties of the [O III] lines and those of the AGN. Our aim was to understand the difference between radio-quiet and radio-loud NLS1s, which may in turn provide useful information on the jet formation mechanism. We find that the NLR gas is much more perturbed in radio-loud than in radio-quiet NLS1s. In particular the NLR dynamics in $\gamma$-ray emitting NLS1s appears to be highly disturbed, and this might be a consequence of interaction with the relativistic jet. The less frequently perturbed NLR in radio-quiet NLS1s suggests instead that these sources likely do not harbor a fully developed relativistic jet. Nonetheless blue-outliers in radio-quiet NLS1s are observed, and we interpret them as a product of strong winds.Comment: 16 pages, 13 figures, 7 tables, accepted for publication on Astronomy & Astrophysic

Exploring the parent population of beamed NLS1s: from the black hole to the jet

The aim of this work is to understand the nature of the parent population of beamed narrow-line Seyfert 1 galaxies (NLS1s), by studying the physical properties of three parent candidates samples: steep-spectrum radio-loud NLS1s, radio-quiet NLS1s and disk-hosted radio-galaxies. In particular, we focused on the black hole mass and Eddington ratio distribution and on the interactions between the jet and the narrow-line region.Comment: 6 pages, 2 figures, to appear in Proceedings of High Energy Phenomena in Relativistic Outflows (HEPRO) V, Workshop Series of the Argentinian Astronomical Societ

Aromatase immunoreactivity in fetal ovine neuronal cell cultures exposed to oxidative injury

A lot of evidence testifies that aromatase is expressed in the central nervous system where it has been detected not only in hypothalamic and limbic regions but also in the cerebral cortex and spinal cord. In physiological conditions, aromatase is expressed exclusively by neurons, where it has been mainly found in cell bodies, processes and synaptic terminals. Moreover, primary cultured cortical astrocytes from female rats are more resistant to oxidant cell death than those from males, suggesting a protective role of estradiol. The aim of this study was to evaluate changes in aromatase expression in response to 3-nitro-L-tyrosine, a marker of oxidative stress, in primary neuronal cell cultures from brains of 60-day old sheep fetuses. Cells were identified as neurons by using class III β-tubulin, a marker of neuronal cells. Two morphological types were consistently recognizable: i) bipolar cells with an oval cell body; ii) multipolar cells whose processes formed a wide net with those of adjacent cells. In situ hybridization technique performed on 60-day old fetal neurons revealed that in baseline conditions aromatase gene expression occurs. Importantly, cells exposed to 360 µM 3-nitro-L-tyrosine were fewer and showed more globular shape and shorter cytoplasmic processes in comparison to control cells. The immunocytochemical study with anti-aromatase antibody revealed that cells exposed to 360 µM 3-nitro-L-tyrosine were significantly more immunoreactive than control cells. Thus, it can be postulated that the oxidant effects of the amino acid analogue 3-nitro-L-tyrosine could be counterbalanced by an increase in aromatase expression that in turn can lead to the formation of neuroprotective estradiol via aromatization of testosterone

Beyond the fundamental noise limit in coherent optical fiber links

It is well known that temperature variations and acoustic noise affect ultrastable frequency dissemination along optical fiber. Active stabilization techniques are in general adopted to compensate for the fiber-induced phase noise. However, despite this compensation, the ultimate link performances remain limited by the so called delay-unsuppressed fiber noise that is related to the propagation delay of the light in the fiber. In this paper, we demonstrate a data post-processing approach which enables us to overcome this limit. We implement a subtraction algorithm between the optical signal delivered at the remote link end and the round-trip signal. In this way, a 6 dB improvement beyond the fundamental limit imposed by delay-unsuppressed noise is obtained. This result enhances the resolution of possible comparisons between remote optical clocks by a factor of 2. We confirm the theoretical prediction with experimental data obtained on a 47 km metropolitan fiber link, and propose how to extend this method for frequency dissemination purposes as well

Unveiling the parent population of beamed narrow-line Seyfert 1s

Narrow-line Seyfert 1 galaxies (NLS1s) are active galactic nuclei (AGN) recently identified as a new class of $\gamma$-ray sources. The high energy emission is explained by the presence of a relativistic jet observed at small angles, just like in the case of blazars. When the latter are observed at larger angles they appear as radio-galaxies, but an analogue parent population for beamed NLS1s has not yet been determined. In this work we analyze this problem by studying the physical properties of three different samples of parent sources candidates: steep-spectrum radio-loud NLS1s, radio-quiet NLS1s, and disk-hosted radio-galaxies, along with compact steep-spectrum sources. In our approach, we first derived black hole mass and Eddington ratio from the optical spectra, then we investigated the interaction between the jet and the narrow-line region from the [O III] $\lambda\lambda$4959,5007 lines. Finally, the radio luminosity function allowed us to compare their jet luminosity and hence determine the relations between the samples.Comment: 6 pages, no figures. Proceedings of the 28th Texas Symposium, Geneva, December 13-18, 201