Androgen-dependent apoptosis in male germ cells is regulated through the proto-oncoprotein Cbl

The proto-oncoprotein Cbl is known to control several signaling processes. It is highly expressed in the testis, and because spermatogenesis is androgen dependent, we investigated the androgen dependency expression of Cbl through its testicular sublocalization and its expression levels in rats that were exposed to the antiandrogen flutamide or were hypophysectomized. We report the androgen dependency of Cbl as it localizes in pachytene spermatocytes during androgen-dependent stages, is down-regulated upon flutamide exposure, and is up-regulated with testosterone in hypophysectomized rats. Coculture experiments showed the key control exerted by the Sertoli cell on Cbl activity. As flutamide induces germ cell apoptosis, we investigate members of the Bcl-2 family upon flutamide exposure. We show that the proapoptotic Bcl-2 family member Bim mirrored Cbl expression through a posttranscriptional process. We also show that in Cbl knockout mouse testes, the imbalance between the high expression of Bim and Smac/Diablo and antiapoptotic factors such as cellular inhibitor of apoptosis 2 favors a survival process, which makes these mice unresponsive to androgen withdrawal and could explain their hypofertility

XUE. Molecular inventory in the inner region of an extremely irradiated Protoplanetary Disk

We present the first results of the eXtreme UV Environments (XUE) James Webb Space Telescope (JWST) program, that focuses on the characterization of planet forming disks in massive star forming regions. These regions are likely representative of the environment in which most planetary systems formed. Understanding the impact of environment on planet formation is critical in order to gain insights into the diversity of the observed exoplanet populations. XUE targets 15 disks in three areas of NGC 6357, which hosts numerous massive OB stars, among which some of the most massive stars in our Galaxy. Thanks to JWST we can, for the first time, study the effect of external irradiation on the inner ($< 10$ au), terrestrial-planet forming regions of proto-planetary disks. In this study, we report on the detection of abundant water, CO, CO$_2$, HCN and C$_2$H$_2$ in the inner few au of XUE 1, a highly irradiated disk in NGC 6357. In addition, small, partially crystalline silicate dust is present at the disk surface. The derived column densities, the oxygen-dominated gas-phase chemistry, and the presence of silicate dust are surprisingly similar to those found in inner disks located in nearby, relatively isolated low-mass star-forming regions. Our findings imply that the inner regions of highly irradiated disks can retain similar physical and chemical conditions as disks in low-mass star-forming regions, thus broadening the range of environments with similar conditions for inner disk rocky planet formation to the most extreme star-forming regions in our Galaxy.Comment: Accepted for publication in ApJ Letters. 20 pages, 7 figure

Workshop to review and progress the reported lists of eu msfd descriptor 3 ( (WKD3LISTS)

info:eu-repo/semantics/publishedVersio

ADP Ribosylation Factor Like 2 (Arl2) Regulates Breast Tumor Aggressivity in Immunodeficient Mice

We have previously reported that ADP ribosylation factor like 2 (Arl2), a small GTPase, content influences microtubule dynamics and cell cycle distribution in breast tumor cells, as well as the degree and distribution of phosphorylated P53. Here we show, in two different human breast adenocarcinoma models, that Arl2 content has a major impact on breast tumor cell aggressivity both in vitro and in vivo. Cells with reduced content of Arl2 displayed reduced contact inhibition, increased clonogenic or cluster formation as well as a proliferative advantage over control cells in an in vitro competition assay. These cells also caused larger tumors in SCID mice, a phenotype which was mimicked by the in vivo administration of siRNA directed against Arl2. Cells with increased Arl2 content displayed reduced aggressivity, both in vitro and in vivo, with enhanced necrosis and were also found to contain increased PP2A phosphatase activity. A rt-PCR analysis of fresh human tumor breast samples suggested that low Arl2 expression was associated with larger tumor size and greater risk of lymph node involvement at diagnosis. These data underline the role of Arl2, a small GTPase, as an important regulator of breast tumor cell aggressivity, both in vitro and in vivo

MINDS. Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI

MIRI/MRS on board the JWST allows us to probe the inner regions of protoplanetary disks. Here we examine the disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core. We focus on the H$_2$O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations. In order to model the molecular features in the spectrum, the continuum was subtracted and LTE slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H$_2$O lines of different excitation conditions, and the slab model fits were performed individually per region. We confidently detect CO, H$_2$O, OH, CO$_2$, and HCN in the emitting layers. The isotopologue H$^{18}_2$O is not detected. Additionally, no other organics, including C$_2$H$_2$, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H$_2$O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. The OH and CO$_2$ emission are relatively weak. It is likely that H$_2$O is not significantly photodissociated; either due to self-shielding against the stellar irradiation, or UV-shielding from small dust particles. The relative emitting strength of the different identified molecular features point towards UV-shielding of H$_2$O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.Comment: Submitted to A&A on May 25 2023. 18 pages, 11 figure

MINDS. The detection of 13^{13}CO2_{2} with JWST-MIRI indicates abundant CO2_{2} in a protoplanetary disk

We present JWST-MIRI MRS spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey (MINDS) GTO program. Emission from $^{12}$CO$_{2}$, $^{13}$CO$_{2}$, H$_{2}$O, HCN, C$_{2}$H$_{2}$, and OH is identified with $^{13}$CO$_{2}$ being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few au of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The $Q$-branches of these molecules, including those of hot-bands, are particularly sensitive to temperature and column density. We find that the $^{12}$CO$_{2}$ emission in the GW Lup disk is coming from optically thick emission at a temperature of $\sim$400 K. $^{13}$CO$_{2}$ is optically thinner and based on a lower temperature of $\sim$325 K, may be tracing deeper into the disk and/or a larger emitting radius than $^{12}$CO$_{2}$. The derived $N_{\rm{CO_{2}}}$/$N_{\rm{H_{2}O}}$ ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on \textit{Spitzer}-IRS data. This high column density ratio may be due to an inner cavity with a radius in between the H$_{2}$O and CO$_{2}$ snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.Comment: 15 pages, 10 figures. Accepted to ApJ

Characterization of Macrophages and Osteoclasts in the Osteosarcoma Tumor Microenvironment at Diagnosis: New Perspective for Osteosarcoma Treatment?

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial. Conventional and multiplex immunohistochemistry of microenvironmental and OS cells were performed on biopsies of 124 OS2006 patients and 17 surgical (“OSNew”) biopsies respectively. CSF-1R (common osteoclast/macrophage progenitor) and TRAP (osteoclast activity) levels in serum of 108 patients were correlated to response to chemotherapy and to prognosis. TRAP levels at surgery and at the end of the protocol were significantly lower in ZA+ than ZA− patients (padj = 0.0011; 0.0132). For ZA+-patients, an increase in the CSF-1R level between diagnosis and surgery and a high TRAP level in the serum at biopsy were associated with a better response to chemotherapy (p = 0.0091; p = 0.0251). At diagnosis, high CD163+ was associated with good prognosis, while low TRAP activity was associated with better overall survival in ZA− patients only. Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163−) mostly residing in osteolytic territories and osteoid-matrix-associated CD68−/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets

PDRs4All II: JWST's NIR and MIR imaging view of the Orion Nebula

The JWST has captured the most detailed and sharpest infrared images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). We investigate the fundamental interaction of far-ultraviolet photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of 0.1-1" (0.0002-0.002 pc or 40-400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. A complex, structured, and folded DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate

PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar

(Abridged) We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the HII region to the atomic PDR (crossing the ionisation front (IF)), and the subsequent transition to the molecular PDR (crossing the dissociation front (DF)). We use high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science Program. The NIRSpec data reveal a forest of lines including, but not limited to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. We observe numerous smaller scale structures whose typical size decreases with distance from Ori C and IR lines from CI, if solely arising from radiative recombination and cascade, reveal very high gas temperatures consistent with the hot irradiated surface of small-scale dense clumps deep inside the PDR. The H2 lines reveal multiple, prominent filaments which exhibit different characteristics. This leaves the impression of a "terraced" transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star- and planet formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&