The Bizarre Spectral Variability of Central Stars of Planetary Nebulae

A radial velocity (RV) survey to detect central stars in binary systems was carried out between 2002 and 2004. De Marco et al. (2004) reported that 10 out of 11 monitored stars exhibited strong RV variability, but periods were not detected. Since other mechanisms, such as wind variability, can cause apparent RV variations, we monitored 4 of the 10 RV-variable stars at echelle resolutions to determine the origin of the variability. Although RV changes are confirmed for all four stars, none of them can be ascribed to binarity at this time. However, only for IC4593 is wind variability able to explain most (though not all) spectral variability. For BD+332642, no wind and no pulsations appear to be the origin of the RV changes. Finally, M1-77 and M2-54, both known to be irregular photometric variables, exhibit dramatic RV and line shape variability of the hydrogen and HeI absorption lines, as well as large RV variability of weaker lines, which do not change in shape. There is no satisfactory explanation of this variability, though a combination of wind variability and pulsations is still the best guess at what makes these stars so variable. We suggest that luminous central stars are ill suited to detect spectroscopic binaries, because winds (and possibly pulsations) are pervasive and would mask even strong periodicities. It it likely that a sample of intrinsically faint central stars would more readily yield binary information.Comment: 7 pages, 3 figures. To appear in the proceedings of the conference "Asymmetric Planetary Nebulae IV

Retinoic acid receptors in acute myeloid leukemia therapy

Retinoic acid (RA) signaling pathways regulate fundamental biological processes, such as cell proliferation, development, differentiation, and apoptosis. Retinoid receptors (RARs and RXRs) are ligand-dependent transcription factors. All-trans retinoic acid (ATRA) is the principal endogenous ligand for the retinoic acid receptor alpha (RARA) and is produced by the enzymatic oxidation of dietary vitamin A, whose deficiency is associated with several pathological conditions. Differentiation therapy using ATRA revolutionized the outcome of acute promyelocytic leukemia (APL), although attempts to replicate these results in other cancer types have been met with more modest results. A better knowledge of RA signaling in different leukemia contexts is required to improve initial designs. Here, we will review the RA signaling pathway in normal and malignant hematopoiesis, and will discuss the advantages and the limitations related to retinoid therapy in acute myeloid leukemia

First Evidence of Circumstellar Disks around Blue Straggler Stars

We present an analysis of optical HST/STIS and HST/FOS spectroscopy of 6 blue stragglers found in the globular clusters M3, NGC6752 and NGC6397. These stars are a subsample of a set of ~50 blue stragglers and stars above the main sequence turn-off in four globular clusters which will be presented in an forthcoming paper. All but the 6 stars presented here can be well fitted with non-LTE model atmospheres. The 6 misfits, on the other hand, possess Balmer jumps which are too large for the effective temperatures implied by their Paschen continua. We find that our data for these stars are consistent with models only if we account for extra absorption of stellar Balmer photons by an ionized circumstellar disk. Column densities of HI and CaII are derived as are the the disks' thicknesses. This is the first time that a circumstellar disk is detected around blue stragglers. The presence of magnetically-locked disks attached to the stars has been suggested as a mechanism to lose the large angular momentum imparted by the collision event at the birth of these stars. The disks implied by our study might not be massive enough to constitute such an angular momentum sink, but they could be the leftovers of once larger disks.Comment: Accepted by ApJ Letters 10 pages, 2 figure

The RCB star V854 Cen is surrounded by a hot dusty shell

Aims : The hydrogen-deficient supergiants known as R Coronae Borealis (RCB) stars might be the result of a double-degenerate merger of two white dwarfs (WDs), or a final helium shell flash in a planetary nebula central star. In this context, any information on the geometry of their circumstellar environment and, in particular, the potential detection of elongated structures, is of great importance. Methods : We obtained near-IR observations of V854 Cen with the AMBER recombiner located at the Very Large Telescope Interferometer (VLTI) array with the compact array (B$\leq$35m) in 2013 and the long array (B$\leq$140m) in 2014. At each time, V854 Cen was at maximum light. The $H$- and $K$-band continua were investigated by means of spectrally dependant geometric models. These data were supplemented with mid-IR VISIR/VLT images. Results : A dusty slightly elongated over density is discovered both in the $H$- and $K$-band images. With the compact array, the central star is unresolved ($\Theta\leq2.5$\,mas), but a flattened dusty environment of $8 \times 11$ mas is discovered whose flux increases from about $\sim$20% in the $H$ band to reach about $\sim$50% at 2.3\micron, which indicates hot (T$\sim$1500\,K) dust in the close vicinity of the star. The major axis is oriented at a position angle (P.A.) of 126$\pm$29$\deg$. Adding the long-array configuration dataset provides tighter constraints on the star diameter ($\Theta\leq1.0$ mas), a slight increase of the overdensity to $12 \times 15$ mas and a consistent P.A. of 133$\pm$49$\deg$. The closure phases, sensitive to asymmetries, are null and compatible with a centro-symmetric, unperturbed environment excluding point sources at the level of 3% of the total flux in 2013 and 2014. The VISIR images exhibit a flattened aspect ratio at the 15-20% level at larger distances ($\sim$1\arcsec) with a position angle of 92$\pm$19$\deg$, marginally consistent with the interferometric observations. Conclusions : This is the first time that a moderately elongated structure has been observed around an RCB star. These observations confirm the numerous suggestions for a bipolar structure proposed for this star in the literature, which were mainly based on polarimetric and spectroscopic observations.Comment: Accepted by A\&A, new version after language editing, Astronomy and Astrophysics (2014

Binary Central Stars of Planetary Nebulae Discovered Through Photometric Variability III: The Central Star of Abell 65

A growing number of close binary stars are being discovered among central stars of planetary nebulae. Recent and ongoing surveys are finding new systems and contributing to our knowledge of the evolution of close binary systems. The push to find more systems was largely based on early discoveries which suggested that 10 to 15% of all central stars are close binaries. One goal of this series of papers is confirmation and classification of these systems as close binaries and determination of binary system parameters. Here we provide time-resolved multi-wavelength photometry of the central star of Abell 65 as well as further analysis of the nebula and discussion of possible binary--nebula connections. Our results for Abell 65 confirm recent work showing that it has a close, cool binary companion, though several of our model parameters disagree with the recently published values. With our longer time baseline of photometric observations from 1989--2009 we also provide a more precise orbital period of 1.0037577 days.Comment: Accepted for publication in the Astronomical Journa

Cytokine exposure mediates transcriptional activation of the orphan nuclear receptor Nur77 in hematopoietic cells

The orphan nuclear receptor Nur77 is an immediate-early response gene that based on tissue and cell context is implicated in a plethora of cellular processes, including proliferation, differentiation, apoptosis, metabolism, and inflammation. Nur77 has a ligand-binding pocket that is obstructed by hydrophobic side groups. Naturally occurring, cell-endogenous ligands have not been identified, and Nur77 transcriptional activity is thought to be regulated through posttranslational modification and modulation of protein levels. To determine whether Nur77 is transcriptionally active in hematopoietic cells in vivo, we used an upstream activating sequence (UAS)-GFP transgenic reporter. We found that Nur77 is transcriptionally inactive in vivo in hematopoietic cells under basal conditions, but that activation occurs following cytokine exposure by G-CSF or IL-3. We also identified a series of serine residues required for cytokine-dependent transactivation of Nur77. Moreover, a kinase inhibitor library screen and proximity labeling-based mass spectrometry identified overlapping kinase pathways that physically interacted with Nur77 and whose inhibition abrogated cytokine-induced activation of Nur77. We determined that transcriptional activation of Nur77 by G-CSF or IL-3 requires functional JAK and mTor signaling since their inhibition leads to Nur77 transcriptional inactivation. Thus, intracellular cytokine signaling networks appear to regulate Nur77 transcriptional activity in mouse hematopoietic cells

V838 Monocerotis: the central star and its environment a decade after outburst

Aims. V838 Monocerotis erupted in 2002, brightened in a series of outbursts, and eventually developed a spectacular light echo. A very red star emerged a few months after the outburst. The whole event has been interpreted as the result of a merger. Methods. We obtained near-IR and mid-IR interferometric observations of V838 Mon with the AMBER and MIDI recombiners located at the Very Large Telescope Interferometer (VLTI) array. The MIDI two-beam observations were obtained with the 8m Unit Telescopes between October 2011 and February 2012. The AMBER three-beam observations were obtained with the compact array (B$\leq$m) in April 2013 and the long array (B$\leq$140m) in May 2014, using the 1.8m Auxiliary Telescopes. Results. A significant new result is the detection of a compact structure around V838 Mon, as seen from MIDI data. The extension of the structure increases from a FWHM of 25 mas at 8 {\mu}m to 70 mas at 13 {\mu}m. At the adopted distance of D = 6.1 $\pm$ 0.6 kpc, the dust is distributed from about 150 to 400 AU around V838 Mon. The MIDI visibilities reveal a flattened structure whose aspect ratio increases with wavelength. The major axis is roughly oriented around a position angle of -10 degrees, which aligns with previous polarimetric studies reported in the literature. This flattening can be interpreted as a relic of the 2002 eruption or by the influence of the currently embedded B3V companion. The AMBER data provide a new diameter for the pseudo-photosphere, which shows that its diameter has decreased by about 40% in 10yrs, reaching a radius R$_*$ = 750 $\pm$ 200 R$_{\odot}$ (3.5 $\pm$ 1.0 AU). Conclusions. After the 2002 eruption, interpreted as the merging of two stars, it seems that the resulting source is relaxing to a normal state. The nearby environment exhibits an equatorial over-density of dust up to several hundreds of AU.Comment: Astronomy and Astrophysics (2014) Will be set by the publishe

Cloud fragmentation and proplyd-like features in HII regions imaged by HST

We have analyzed HST ACS and WFPC2 new and archival images of eight HII regions to look for new proto-planetary disks (proplyds) similar to those found in the Orion Nebula. We find a wealth of features similar in size (though many are larger) to the bright cusps around the Orion Nebula proplyds. None of them, however, contains a definitive central star. From this, we deduce that the new cusps may not be proplyds, but instead are fragments of molecular cloud material. Out of all the features found in the eight HII regions examined, only one, an apparent edge-on silhouette in M17, may have a central star. This feature might join the small number of bona fide proplyds found outside the Orion Nebula, in M8, M20 and possibly in M16. In line with the results found recently by Smith et al. (2005), the paucity of proplyds outside the Orion Nebula, may be explained by their transient nature as well as by the specific environmental conditions under whichthey can be observed.Comment: 51 pages; 19 figures; 5 tables. Accepted by A

RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from those of two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacological antagonists, suggesting it may be ligand-independent. These data provide further evidence that activated retinoid X receptors can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of retinoid X receptors in other settings

RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from those of two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacological antagonists, suggesting it may be ligand-independent. These data provide further evidence that activated retinoid X receptors can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of retinoid X receptors in other settings.This work was supported by National Institutes of Health grant R01 HL128447 (JSW) , by the Siteman Investment Program (JSW) , the Washington University SPORE DRP (JSW and MAF) , the Children's Discovery Institute (JSW) , the Alex's Lemonade Stand Foundation Young Investigator Award (MAF) , the National Institutes of Health 5K12HD07622408 (MAF) , and grants from the Spanish Ministerio de Ciencia e Innovacion (MCI) (SAF2017-90604-REDT-NurCaMeIn, RTI2018-095928-BI00) (MR).S