The ZNF217 Biomarker Predicts Low- and High-Risk Oncotype DX® Recurrence Score in ER-Positive Invasive Breast Cancers

We assessed mRNA and protein expression levels of the ZN217 oncogene in 17 clinical FFPE ER-positive invasive breast cancer specimens with known (low or high) Oncotype DX® Recurrence Scores. This study shows that mRNA or nuclear protein levels of the ZNF217 significantly correlate with Oncotype DX® Recurrence Score

ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>ZNF217 is a candidate oncogene located at 20q13, a chromosomal region frequently amplified in breast cancers. The precise mechanisms involved in ZNF217 pro-survival function are currently unknown, and utmost importance is given to deciphering the role of ZNF217 in cancer therapy response.</p> <p>Results</p> <p>We provide evidence that stable overexpression of ZNF217 in MDA-MB-231 breast cancer cells conferred resistance to paclitaxel, stimulated cell proliferation <it>in vitro </it>associated with aberrant expression of several cyclins, and increased tumor growth in mouse xenograft models. Conversely, siRNA-mediated silencing of ZNF217 expression in MCF7 breast cancer cells, which possess high endogenous levels of ZNF217, led to decreased cell proliferation and increased sensitivity to paclitaxel. The paclitaxel resistance developed by ZNF217-overexpressing MDA-MB-231 cells was not mediated by the ABCB1/PgP transporter. However, ZNF217 was able to counteract the apoptotic signals mediated by paclitaxel as a consequence of alterations in the intrinsic apoptotic pathway through constitutive deregulation of the balance of Bcl-2 family proteins. Interestingly, ZNF217 expression levels were correlated with the oncogenic kinase Aurora-A expression levels, as ZNF217 overexpression led to increased expression of the Aurora-A protein, whereas ZNF217 silencing was associated with low Aurora-A expression levels. We showed that a potent Aurora-A kinase inhibitor was able to reverse paclitaxel resistance in the ZNF217-overexpressing cells.</p> <p>Conclusion</p> <p>Altogether, these data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects.</p

Young Stellar Objects and Triggered Star Formation in the Vulpecula OB Association

The Vulpecula OB association, VulOB1, is a region of active star formation located in the Galactic plane at 2.3 kpc from the Sun. Previous studies suggest that sequential star formation is propagating along this 100 pc long molecular complex. In this paper, we use Spitzer MIPSGAL and GLIMPSE data to reconstruct the star formation history of VulOB1, and search for signatures of past triggering events. We make a census of Young Stellar Objects (YSO) in VulOB1 based on IR color and magnitude criteria, and we rely on the properties and nature of these YSOs to trace recent episodes of massive star formation. We find 856 YSO candidates, and show that the evolutionary stage of the YSO population in VulOB1 is rather homogeneous - ruling out the scenario of propagating star formation. We estimate the current star formation efficiency to be ~8 %. We also report the discovery of a dozen pillar-like structures, which are confirmed to be sites of small scale triggered star formation.Comment: 30 pages, 11 figures, accepted for publication in Ap

Evaluating ZNF217 mRNA Expression Levels as a Predictor of Response to Endocrine Therapy in ER+ Breast Cancer

ZNF217 is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we aimed at investigating in a pilot prospective study the association between ZNF217 mRNA expression levels and the clinical response to neoadjuvant endocrine therapy (ET) in postmenopausal ER-positive (ER C) breast cancer patients. Core surgical biopsy samples before treatment initiation and post-treatment were obtained from 68 patients, and Ki-67 values measured by immunohistochemistry (IHC) were used to identify responders (n = 59) and non-responders (n = 9) after 4 months of ET. We report for the first time that high ZNF217 mRNA expression level measured by RT-qPCR in the initial tumor samples (pre-treatment) is associated with poor response to neoadjuvant ET. Indeed, the clinical positive response rate in patients with low ZNF217 expression levels was significantly higher than that in those with high ZNF217 expression levels (P = 0.027). Additionally, a retrospective analysis evaluating ZNF217 expression levels in primary breast tumor of ER+/HER2-/LNO breast cancer patients treated with adjuvant ET enabled the identification of poorer responders prone to earlier relapse (P = 0.013), while ZNF217 did not retain any prognostic value in the ER+/HER2-/LNO breast cancer patients who did not receive any treatment. Altogether, these data suggest that ZNF217 expression might be predictive of clinical response to ET

A Strong-Lensing Model for the WMDF JWST/GTO Very Rich Cluster Abell 1489

We present a first strong-lensing model for the galaxy cluster RM J121218.5+273255.1 ($z=0.35$; hereafter RMJ1212; also known as Abell 1489). This cluster is amongst the top 0.1\% richest clusters in the redMaPPer catalog; it is significantly detected in X-ray and through the Sunyaev-Zel'dovich effect in ROSAT and \emph{Planck} data, respectively; and its optical luminosity distribution implies a very large lens, following mass-to-light scaling relations. Based on these properties it was chosen for the Webb Medium Deep Fields (WMDF) JWST/GTO program. In preparation for this program, RMJ1212 was recently imaged with GMOS on Gemini North and in seven optical and near-infrared bands with the \emph{Hubble Space Telescope}. We use these data to map the inner mass distribution of the cluster, uncovering various sets of multiple images. We also search for high-redshift candidates in the data, as well as for transient sources. We find over a dozen high-redshift ($z\gtrsim6$) candidates based on both photometric redshift and the dropout technique. No prominent ($\gtrsim5 \sigma$) transients were found in the data between the two HST visits. Our lensing analysis reveals a relatively large lens with an effective Einstein radius of $\theta_{E}\simeq32\pm3''$ ($z_{s}=2$), in broad agreement with the scaling-relation expectations. RMJ1212 demonstrates that powerful lensing clusters can be selected in a robust and automated way following the light-traces-mass assumption.Comment: 17 pages, 6 figures, 2 tables; To be submitte

Herschel-ATLAS: Far-infrared properties of radio-loud and radio-quiet quasars

This is pre-copyedited, author-produced pdf of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record, E. Kalfountzou, et al., ‘Herschel-ATLAS: Far-infrared properties of radio-loud and radio-quiet quasars’, MNRAS, Vol 42(2): 1181-1196, first published online June 11, 2014, is available online via doi: 10.1093/mnras/stu782 Published by Oxford University Press on behalf of the Royal Astronomical Society.We have constructed a sample of radio-loud and radio-quiet quasars from the Faint Images Radio Sky at Twenty-one centimetres and the Sloan Digital Sky Survey Data Release 7, over the Herschel-ATLAS Phase 1 area (9h, 12h and 14 h . 5 ). Using a stacking analysis, we find a significant correlation between the far-infrared (FIR) luminosity and 1.4-GHz luminosity for radio-loud quasars. Partial correlation analysis confirms the intrinsic correlation after removing the redshift contribution, while for radio-quiet quasars, no partial correlation is found. Using a single-temperature grey-body model, we find a general trend of lower dust temperatures in case of radio-loud quasars compared to radio-quiet quasars. Also, radio-loud quasars are found to have almost constant mean values of dust mass along redshift and optical luminosity bins. In addition, we find that radio-loud quasars at lower optical luminosities tend to have on average higher FIR and 250-μm luminosity with respect to radio-quiet quasars with the same optical luminosites. Even if we use a two-temperature grey-body model to describe the FIR data, the FIR luminosity excess remains at lower optical luminosities. These results suggest that powerful radio jets are associated with star formation especially at lower accretion ratesPeer reviewe

Are JWST/NIRCam color gradients in the lensed z=2.3 dusty star-forming galaxy El Anzuelo due to central dust attenuation or inside-out galaxy growth?

Gradients in the mass-to-light ratio of distant galaxies impede our ability to characterize their size and compactness. The long-wavelength filters of $JWST$'s NIRCam offer a significant step forward. For galaxies at Cosmic Noon ($z\sim2$), this regime corresponds to the rest-frame near-infrared, which is less biased towards young stars and captures emission from the bulk of a galaxy's stellar population. We present an initial analysis of an extraordinary lensed dusty star-forming galaxy (DSFG) at $z=2.3$ behind the $El~Gordo$ cluster ($z=0.87$), named $El~Anzuelo$ ("The Fishhook") after its partial Einstein-ring morphology. The FUV-NIR SED suggests an intrinsic star formation rate of $81^{+7}_{-2}~M_\odot~{\rm yr}^{-1}$ and dust attenuation $A_V\approx 1.6$, in line with other DSFGs on the star-forming main sequence. We develop a parametric lens model to reconstruct the source-plane structure of dust imaged by the Atacama Large Millimeter/submillimeter Array, far-UV to optical light from $Hubble$, and near-IR imaging with 8 filters of $JWST$/NIRCam, as part of the Prime Extragalactic Areas for Reionization and Lensing Science (PEARLS) program. The source-plane half-light radius is remarkably consistent from $\sim 1-4.5~\mu$m, despite a clear color gradient where the inferred galaxy center is redder than the outskirts. We interpret this to be the result of both a radially-decreasing gradient in attenuation and substantial spatial offsets between UV- and IR-emitting components. A spatial decomposition of the SED reveals modestly suppressed star formation in the inner kiloparsec, which suggests that we are witnessing the early stages of inside-out quenching.Comment: 29 pages, 11 figures, 5 tables. Accepted for publication in Ap

Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization

Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition

JWST's PEARLS: a new lens model for ACT-CL J0102−-4915, "EL Gordo'', and the first red supergiant star at cosmological distances discovered by JWST

The first JWST data on the massive colliding cluster El Gordo confirm 23 known families of multiply lensed images and identify 8 new members of these families. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and 9 were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range $2<z<6$. The derived dark-matter distribution confirms the double-peak configuration of mass found by earlier work with the southern and northern clumps having similar masses. We confirm that El Gordo is the most massive known cluster at $z>0.8$ and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at $z=0.87$ and has an estimated mass of $3.8\times10^9$~\Msol, making it the smallest substructure found at $z>0.5$. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at $z=2.1878$. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at $z>6$, making more of them visible than in blank fields of similar size, but there appears to be a deficiency of such objects.Comment: 27 pages, 21 figure