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

Mesoscale theory of grains and cells: crystal plasticity and coarsening

Solids with spatial variations in the crystalline axes naturally evolve into cells or grains separated by sharp walls. Such variations are mathematically described using the Nye dislocation density tensor. At high temperatures, polycrystalline grains form from the melt and coarsen with time: the dislocations can both climb and glide. At low temperatures under shear the dislocations (which allow only glide) form into cell structures. While both the microscopic laws of dislocation motion and the macroscopic laws of coarsening and plastic deformation are well studied, we hitherto have had no simple, continuum explanation for the evolution of dislocations into sharp walls. We present here a mesoscale theory of dislocation motion. It provides a quantitative description of deformation and rotation, grounded in a microscopic order parameter field exhibiting the topologically conserved quantities. The topological current of the Nye dislocation density tensor is derived from a microscopic theory of glide driven by Peach-Koehler forces between dislocations using a simple closure approximation. The resulting theory is shown to form sharp dislocation walls in finite time, both with and without dislocation climb.Comment: 5 pages, 3 figure

Blazar Flaring Patterns (B-FlaP): Classifying Blazar Candidates of Uncertain type in the third Fermi-LAT catalog by Artificial Neural Networks

The Fermi Large Area Telescope (LAT) is currently the most important facility for investigating the GeV $\gamma$-ray sky. With Fermi LAT more than three thousand $\gamma$-ray sources have been discovered so far. 1144 ($\sim40\%$) of the sources are active galaxies of the blazar class, and 573 ($\sim20\%$) are listed as Blazar Candidate of Uncertain type (BCU), or sources without a conclusive classification. We use the Empirical Cumulative Distribution Functions (ECDF) and the Artificial Neural Networks (ANN) for a fast method of screening and classification for BCUs based on data collected at $\gamma$-ray energies only, when rigorous multiwavelength analysis is not available. Based on our method, we classify 342 BCUs as BL Lacs and 154 as FSRQs, while 77 objects remain uncertain. Moreover, radio analysis and direct observations in ground-based optical observatories are used as counterparts to the statistical classifications to validate the method. This approach is of interest because of the increasing number of unclassified sources in Fermi catalogs and because blazars and in particular their subclass High Synchrotron Peak (HSP) objects are the main targets of atmospheric Cherenkov telescopes.Comment: 18 pages, 17 figures, accepted for publication on MNRA

From carbon dependence to renewables: The European oil majors' strategies to face climate change

International oil companies play a central role in the transition towards a low-carbon economy. These companies have the leadership and influence to advance technological alternatives or sustain the current dependence on fossil fuels. This article aims to analyse the decarbonisation strategies that European oil companies are performing in the wake of climate change. A document analysis was integrated with carbon emission data from 10 European international oil companies and uncovered the four main strategies adopted by companies: sustained carbon dependence, carbon emissions compensation, carbon emissions mitigation and carbon independence. The results indicate that companies have adopted variable levels of action, despite their overlapping discourse on climate mitigation, with only one of the analysed firms performing a transition away from fossil fuels

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

Optical counterparts of undetermined type γ\gamma-ray Active Galactic Nuclei with blazar-like Spectral Energy Distributions

During its first four years of scientific observations, the Fermi Large Area Telescope (Fermi-LAT) detected 3033 $\gamma$-ray sources above a 4$\sigma$ significance level. Although most of the extra-Galactic sources are active galactic nuclei (AGN) of the blazar class, other families of AGNs are observed too, while a still high fraction of detections ($\sim 30\%$) remains with uncertain association or classification. According to the currently accepted interpretation, the AGN $\gamma$-ray emission arises from inverse Compton (IC) scattering of low energy photons by relativistic particles confined in a jet that, in the case of blazars, is oriented very close to our line of sight. Taking advantage of data from radio and X-ray wavelengths, which we expect to be produced together with $\gamma$-rays, providing a much better source localization potential, we focused our attention on a sample of $\gamma$-ray Blazar Candidates of Undetermined Type (BCUs), starting a campaign of optical spectroscopic observations. The main aims of our investigation include a census of the AGN families that contribute to $\gamma$-ray emission and a study of their redshift distribution, with the subsequent implications on the intrinsic source power. We furthermore analyze which $\gamma$-ray properties can better constrain the nature of the source, thus helping in the study of objects not yet associated with a reliable low frequency counterpart. In this communication we report on the instruments and techniques used to identify the optical counterparts of $\gamma$-ray sources, we give an overview on the status of our work, and we discuss the implications of a large scale study of $\gamma$-ray emitting AGNs.Comment: 9 pages, 2 figures, proceedings of the 10th Serbian Conference on Spectral Line Shapes in Astrophysics. JOAA, accepte