The Type IIn Supernova SN 2010bt: The Explosion of a Star in Outburst

Indexación: Scopus.It is well known that massive stars (M > 8 M ) evolve up to the collapse of the stellar core, resulting in most cases in a supernova (SN) explosion. Their heterogeneity is related mainly to different configurations of the progenitor star at the moment of the explosion and to their immediate environments. We present photometry and spectroscopy of SN 2010bt, which was classified as a Type IIn SN from a spectrum obtained soon after discovery and was observed extensively for about 2 months. After the seasonal interruption owing to its proximity to the Sun, the SN was below the detection threshold, indicative of a rapid luminosity decline. We can identify the likely progenitor with a very luminous star (log L/L ≈ 7) through comparison of Hubble Space Telescope images of the host galaxy prior to explosion with those of the SN obtained after maximum light. Such a luminosity is not expected for a quiescent star, but rather for a massive star in an active phase. This progenitor candidate was later confirmed via images taken in 2015 (∼5 yr post-discovery), in which no bright point source was detected at the SN position. Given these results and the SN behavior, we conclude that SN 2010bt was likely a Type IIn SN and that its progenitor was a massive star that experienced an outburst shortly before the final explosion, leading to a dense H-rich circumstellar environment around the SN progenitor. © 2018. The American Astronomical Society. All rights reserved.https://iopscience.iop.org/article/10.3847/1538-4357/aac51

Translating the Game: Ribosomes as Active Players

Ribosomes have been long considered as executors of the translational program. The fact that ribosomes can control the translation of specific mRNAs or entire cellular programs is often neglected. Ribosomopathies, inherited diseases with mutations in ribosomal factors, show tissue specific defects and cancer predisposition. Studies of ribosomopathies have paved the way to the concept that ribosomes may control translation of specific mRNAs. Studies in Drosophila and mice support the existence of heterogeneous ribosomes that differentially translate mRNAs to coordinate cellular programs. Recent studies have now shown that ribosomal activity is not only a critical regulator of growth but also of metabolism. For instance, glycolysis and mitochondrial function have been found to be affected by ribosomal availability. Also, ATP levels drop in models of ribosomopathies. We discuss findings highlighting the relevance of ribosome heterogeneity in physiological and pathological conditions, as well as the possibility that in rate-limiting situations, ribosomes may favor some translational programs. We discuss the effects of ribosome heterogeneity on cellular metabolism, tumorigenesis and aging. We speculate a scenario in which ribosomes are not only executors of a metabolic program but act as modulators

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible

HAWK-I infrared supernova search in starburst galaxies

The use of SN rates to probe explosion scenarios and to trace the cosmic star formation history received a boost from a number of synoptic surveys. There has been a recent claim of a mismatch by a factor of two between star formation and core collapse SN rates, and different explanations have been proposed for this discrepancy.} We attempted an independent test of the relation between star formation and supernova rates in the extreme environment of starburst galaxies, where both star formation and extinction are extremely high. To this aim we conducted an infrared supernova search in a sample of local starburts galaxies. The rational to search in the infrared is to reduce the bias due to extinction, which is one of the putative reasons for the observed discrepancy between star formation and supernova rates. To evaluate the outcome of the search we developed a MonteCarlo simulation tool that is used to predict the number and properties of the expected supernovae based on the search characteristics and the current understanding of starburst galaxies and supernovae. During the search we discovered 6 supernovae (4 with spectroscopic classification) which is in excellent agreement with the prediction of the MonteCarlo simulation tool that is, on average, $5.3\pm2.3$ events. The number of supernovae detected in starburst galaxies is consistent with that predicted from their high star formation rate when we recognize that a major fraction ($\sim 60$) of the events remains hidden in the unaccessible, high density nuclear regions because of a combination of reduced search efficiency and high extinction.Comment: 17 pages, 10 figures. Accepted for publication in A&

po 130 ser235 residue drives eif6 oncogenic activity in npm alk induced t cell lymphomagenesis

Introduction Dysregulation of mRNA translational control in cancer leads to cell transformation, metabolic reprogramming and angiogenesis. eIF6 is an oncogenic translation factor, which regulates the initiation phase of translation acting on 60S availability in the cytoplasm and controlling active 80S complex formation. eIF6 activation is mTORC1-independent and driven by PKCβ mediated phosphorylation on Ser235. An increment of eIF6 expression is reported in several cancer cell lines and human tumours, due to amplification or overexpression. In mice, eIF6 haploinsufficiency blocks Myc-driven lymphomagenesis. Intriguingly, high levels of PKC and eIF6 are found in T-cell lymphomas. In particular, in Anaplastic Large Cell Lymphoma (ALCL) eIF6 is overexpressed and hyperactivated. Material and methods Here, we aimed to define the role of eIF6 phosphorylation in NPM-ALK mediated T-cell lymphomagenesis, combining multidisciplinary studies on murine and cellular models. We used a conditional eIF6 SA KI mouse model in which Ser235 is replaced by an Ala. Results and discussions First, we addressed the effect of eIF6 mutated protein expression in all tissues: homozygosity is lethal after gastrulation while heterozygous mice are viable but resistant to NPM-ALK driven lymphomagenesis. Then, we investigated the role of Ser235 phosphorylation specifically in T-cell lineage, crossing eIF6 SA KI mice with CD4-Cre mice. Physiological T-cell development and subsets composition are not affected by the eIF6 mutated protein. In cancer, eIF6 SA/SA CD4-Cre NPM-ALK mice have a significant increase in survival time, compared to wt with a delay in the appearance of lymphoma up to 6 months. Histological analysis and ex vivo cultures confirm the delay in disease development. eIF6 SA/SA CD4-Cre NPM-ALK thymocytes are smaller respect to wt counterparts and show a striking senescence-like phenotype in vitro . Similarly, in vitro generated eIF6 SA/SA MEFs show a markedly reduced proliferation and increased SA β-gal positivity. This phenotype is completely rescued by transducing eIF6 wild-type, but not by eIF6 SA . Currently, we are investigating the molecular mechanisms by which eIF6 phosphorylation affects ALK-induced malignancy and whether it may modulate premature cell senescence, thus establishing an effective barrier to T-cell lymphomagenesis. Conclusion Our work demonstrates for the first time that eIF6 phosphorylation plays an essential role in mammals development, cell homeostasis and is rate-limiting for T-cell lymphomagenesis in vivo

The Type IIn Supernova SN 2010bt: The Explosion of a Star in Outburst

It is well known that massive stars (M > 8M(circle dot)) evolve up to the collapse of the stellar core, resulting in most cases in a supernova (SN) explosion. Their heterogeneity is related mainly to different configurations of the progenitor star at the moment of the explosion and to their immediate environments. We present photometry and spectroscopy of SN. 2010bt, which was classified as a Type. IIn. SN from a spectrum obtained soon after discovery and was observed extensively for about 2 months. After the seasonal interruption owing to its proximity to the Sun, the SN was below the detection threshold, indicative of a rapid luminosity decline. We can identify the likely progenitor with a very luminous star (log L/L-circle dot approximate to 7) through comparison of Hubble Space Telescope images of the host galaxy prior to explosion with those of the SN obtained after maximum light. Such a luminosity is not expected for a quiescent star, but rather for a massive star in an active phase. This progenitor candidate was later confirmed via images taken in 2015 (similar to 5 yr post-discovery), in which no bright point source was detected at the SN position. Given these results and the SN behavior, we conclude that SN. 2010bt was likely a Type IIn SN and that its progenitor was a massive star that experienced an outburst shortly before the final explosion, leading to a dense H-rich circumstellar environment around the SN progenitor

Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors

Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all these processes. Here, we show that, in human cells, impaired rRNA processing, caused by expressing an interfering mutant of BOP1 or by knocking down components of the PeBoW complex elicits activation of mTORC1 signalling. This leads to enhanced phosphorylation of its substrates S6K1 and 4E-BP1, and stimulation of proteins involved in translation initiation and elongation. In particular, we observe both inactivation and downregulation of the eukaryotic elongation factor 2 kinase, which normally inhibits translation elongation. The latter effect involves decreased expression of the eEF2K mRNA. The mRNAs for ribosomal proteins, whose translation is positively regulated by mTORC1 signalling, also remain associated with ribosomes. Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production

Massive stars exploding in a He-rich circumstellar medium. IV. Transitional Type Ibn Supernovae

We present ultraviolet, optical and near-infrared data of the Type Ibn supernovae (SNe) 2010al and 2011hw. SN 2010al reaches an absolute magnitude at peak of M(R) = -18.86 +- 0.21. Its early light curve shows similarities with normal SNe Ib, with a rise to maximum slower than most SNe Ibn. The spectra are dominated by a blue continuum at early stages, with narrow P-Cygni He I lines indicating the presence of a slow-moving, He-rich circumstellar medium. At later epochs the spectra well match those of the prototypical SN Ibn 2006jc, although the broader lines suggest that a significant amount of He was still present in the stellar envelope at the time of the explosion. SN 2011hw is somewhat different. It was discovered after the first maximum, but the light curve shows a double-peak. The absolute magnitude at discovery is similar to that of the second peak (M(R) = -18.59 +- 0.25), and slightly fainter than the average of SNe Ibn. Though the spectra of SN 2011hw are similar to those of SN 2006jc, coronal lines and narrow Balmer lines are cleary detected. This indicates substantial interaction of the SN ejecta with He-rich, but not H-free, circumstellar material. The spectra of SN 2011hw suggest that it is a transitional SN Ibn/IIn event similar to SN 2005la. While for SN 2010al the spectro-photometric evolution favours a H-deprived Wolf-Rayet progenitor (of WN-type), we agree with the conclusion of Smith et al. (2012) that the precursor of SN 2011hw was likely in transition from a luminous blue variable to an early Wolf-Rayet (Ofpe/WN9) stage.Comment: 23 pages, 11 figures, 6 tables. Accepted by MNRA

Type Ia supernovae with and without blueshifted narrow Na I D lines - how different is their structure?

In studies on intermediate- and high-resolution spectra of Type Ia supernovae (SNe Ia), some objects exhibit narrow Na I D absorptions often blueshifted with respect to the rest wavelength within the host galaxy. The absence of these in other SNe Ia may reflect that the explosions have different progenitors: blueshifted Na I D features might be explained by the outflows of ‘single-degenerate’ systems (binaries of a white dwarf with a non-degenerate companion). In this work, we search for systematic differences among SNe Ia for which the Na I D characteristics have been clearly established in previous studies. We perform an analysis of the chemical abundances in the outer ejecta of 13 ‘spectroscopically normal’ SNe Ia (five of which show blueshifted Na lines), modelling time series of photospheric spectra with a radiative-transfer code. We find only moderate differences between ‘blueshifted-Na’, ‘redshifted-Na’ and ‘no-Na’ SNe Ia, so that we can neither conclusively confirm a ‘one-scenario’ nor a ‘two-scenario’ theory for normal SNe Ia. Yet, some of the trends we see should be further studied using larger observed samples: models for blueshifted-Na SNe tend to show higher photospheric velocities than no-Na SNe, corresponding to a higher opacity of the envelope. Consistently, blueshifted-Na SNe show hints of a somewhat larger iron-group content in the outer layers with respect to the no-Na subsample (and also to the redshifted-Na subsample). This agrees with earlier work where it was found that the light curves of no-Na SNe – often appearing in elliptical galaxies – are narrower, that is, decline more rapidly

MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state

Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes are difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. Furthermore, we demonstrate that the MYC-driven epigenetic reprogramming favors the formation and maintenance of tumor-initiating cells endowed with metastatic capacity. This study supports the notion that MYC-driven tumor initiation relies on cell reprogramming, which is mediated by the activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers