HST survey of the Orion Nebula Cluster in the H2_2O 1.4 μ\mum absorption band: I. A census of substellar and planetary mass objects

In order to obtain a complete census of the stellar and sub-stellar population, down to a few M$_{Jup}$ in the $\sim1$ Myr old Orion Nebula Cluster, we used the infrared channel of the Wide Field Camera 3 of the Hubble Space Telescope with the F139M and F130N filters. These bandpasses correspond to the $1.4 \mu$m H$_2$O absorption feature and an adjacent line-free continuum region. Out of $4,504$ detected sources, $3,352$ (about $75\%$) appear fainter than m$_{130}=14$ (Vega mag) in the F130N filter, a brightness corresponding to the hydrogen-burning limit mass (M$\simeq 0.072 M_\odot$) at $\sim 1$ Myr. Of these, however, only $742$ sources have a negative F130M-139N color index, indicative of the presence of H$_2$O vapor in absorption, and can therefore be classified as bona-fide M and L dwarfs, with effective temperatures T$\lesssim 2850$ K at an assumed $1$ Myr cluster age. On our color-magnitude diagram, this population of sources with H$_2$O absorption appears clearly distinct from the larger background population of highly reddened stars and galaxies with positive F130M-F139N color index, and can be traced down to the sensitivity limit of our survey, m$_{130}\simeq 21.5$, corresponding to a $1$ Myr old $\simeq 3$M$_{Jup}$, planetary mass object under about 2 magnitudes of visual extinction. Theoretical models of the BT-Settl family predicting substellar isochrones of $1, 2$ and $3$ Myr (down to $\sim 1$M$_{Jup}$) fail to reproduce the observed H$_2$O color index at M$\lesssim 20$M$_{Jup}$. We perform a Bayesian analysis to determine extinction, mass and effective temperature of each sub-stellar member of our sample, together with its membership probability.Comment: Accepted for publication in the Astrophysical Journal. The resolution of several figures has been downgraded to comply with the size limit of arXiv submission

HST Survey of the Orion Nebula Cluster in the H₂O 1.4 μm Absorption Band. I. A Census of Substellar and Planetary-mass Objects

In order to obtain a complete census of the stellar and substellar population, down to a few M_(Jup) in the ~1 Myr old Orion Nebula Cluster, we used the infrared channel of the Wide Field Camera 3 of the Hubble Space Telescope with the F139M and F130N filters. These bandpasses correspond to the 1.4 μm H₂O absorption feature and an adjacent line-free continuum region. Out of 4504 detected sources, 3352 (about 75%) appear fainter than m₁₃₀ = 14 (Vega mag) in the F130N filter, a brightness corresponding to the hydrogen-burning limit mass M ≃ 0.072 M_⊙) at ~1 Myr. Of these, however, only 742 sources have a negative F130M–F139N color index, indicative of the presence of H₂O vapor in absorption, and can therefore be classified as bona fide M and L dwarfs, with effective temperatures T ≾ 2850 K at an assumed 1 Myr cluster age. On our color–magnitude diagram (CMD), this population of sources with H₂O absorption appears clearly distinct from the larger background population of highly reddened stars and galaxies with positive F130M–F139N color index and can be traced down to the sensitivity limit of our survey, m₁₃₀ ≃ 21.5, corresponding to a 1 Myr old ≃ 3 M_(Jup) planetary-mass object under about 2 mag of visual extinction. Theoretical models of the BT-Settl family predicting substellar isochrones of 1, 2, and 3 Myr down to ~1 M_(Jup) fail to reproduce the observed H₂O color index at M ≾ 20 M_(Jup). We perform a Bayesian analysis to determine extinction, mass, and effective temperature of each substellar member of our sample, together with its membership probability

X-shooter spectroscopy of young stars with disks. The TW Hydrae association as a probe of the final stages of disk accretion

Context. Measurements of the fraction of disk-bearing stars in clusters as a function of age indicate protoplanetary disk lifetimes ≲10 Myr. However, our knowledge of the time evolution of mass accretion in young stars over the disk lifespans is subject to many uncertainties, especially at the lowest stellar masses (M⋆). Aims: We investigate ongoing accretion activity in young stars in the TW Hydrae association (TWA). The age of the association (∼8-10 Myr) renders it an ideal target for probing the final stages of disk accretion, and its proximity (∼50 pc) enables a detailed assessment of stellar and accretion properties down to brown dwarf masses. Methods: Our sample comprises eleven TWA members with infrared excess, amounting to 85% of the total TWA population with disks. Our targets span spectral types between M0 and M9, and masses between 0.58 M☉ and 0.02 M☉. We employed homogeneous spectroscopic data from 300 nm to 2500 nm, obtained synoptically with the X-shooter spectrograph, to derive the individual extinction, stellar parameters, and accretion parameters for each object simultaneously. We then examined the luminosity of Balmer lines and forbidden emission lines to probe the physics of the star-disk interaction environment. Results: Disk-bearing stars represent around 24% of the total TWA population. We detected signatures of ongoing accretion for 70% of our TWA targets for which accurate measurements of the stellar parameters could be derived. This implies a fraction of accretors between 13-17% across the entire TWA (that accounts for the disk-bearing and potentially accreting members not included in our survey). The spectral emission associated with these stars reveals a more evolved stage of these accretors compared to younger PMS populations studied with the same instrument and analysis techniques (e.g., Lupus): first, a large fraction (∼50%) exhibit nearly symmetric, narrow Hα line profiles; second, over 80% of them exhibit Balmer decrements that are consistent with moderate accretion activity and optically thin emission; third, less than a third exhibit forbidden line emission in [O I] 6300 Å, which is indicative of winds and outflows activity; and fourth, only one sixth exhibit signatures of collimated jets. However, the distribution in accretion rates (Ṁacc) derived for the TWA sample closely follows that of younger regions (Lupus, Chamaeleon I, σ Orionis) over the mass range of overlap (M⋆ ∼ 0.1-0.3 M☉). An overall correlation between Ṁacc and M⋆ is detected and best reproduced by the function Ṁacc ∝ M∝2.1±0.5. Conclusion. At least in the lowest M⋆ regimes, stars that still retain a disk at ages ∼8-10 Myr are found to exhibit statistically similar, albeit moderate, accretion levels as those measured around younger objects. This "slow" Ṁacc evolution that is apparent at the lowest masses may be associated with longer evolutionary timescales of disks around low-mass stars, which is suggested by the mass-dependent disk fractions reported in the literature within individual clusters. Reduced spectra are also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/cat/J/A+A/632/A46 Based on observations collected at the European Southern Observatory under ESO programs 084.C-0269(B), 085.C-0238(A), 086.C-0173(A), 087.C-0244(A), 287.C-5039(A), 089.C-0143(A), 093.C-0097(A), and 095.C-0147(A)

An anatomy-based lumped parameter model of cerebrospinal venous circulation: can an extracranial anatomical change impact intracranial hemodynamics?

Background The relationship between extracranial venous system abnormalities and central nervous system disorders has been recently theorized. In this paper we delve into this hypothesis by modeling the venous drainage in brain and spinal column areas and simulating the intracranial flow changes due to extracranial morphological stenoses. Methods A lumped parameter model of the cerebro-spinal venous drainage was created based on anatomical knowledge and vessels diameters and lengths taken from literature. Each vein was modeled as a hydraulic resistance, calculated through Poiseuille’s law. The inputs of the model were arterial flow rates of the intracranial, vertebral and lumbar districts. The effects of the obstruction of the main venous outflows were simulated. A database comprising 112 Multiple Sclerosis patients (Male/Female = 42/70; median age ± standard deviation = 43.7 ± 10.5 years) was retrospectively analyzed. Results The flow rate of the main veins estimated with the model was similar to the measures of 21 healthy controls (Male/Female = 10/11; mean age ± standard deviation = 31 ± 11 years), obtained with a 1.5 T Magnetic Resonance scanner. The intracranial reflux topography predicted with the model in cases of internal jugular vein diameter reduction was similar to those observed in the patients with internal jugular vein obstacles. Conclusions The proposed model can predict physiological and pathological behaviors with good fidelity. Despite the simplifications introduced in cerebrospinal venous circulation modeling, the key anatomical feature of the lumped parameter model allowed for a detailed analysis of the consequences of extracranial venous impairments on intracranial pressure and hemodynamics

The emerging role of insulin-like growth factor 1 receptor (IGF1r) in gastrointestinal stromal tumors (GISTs)

Recent years have seen a growing interest in insulin-like growth factor 1 receptor (IGF1R) in medical oncology. Interesting data have been reported also on IGF1r in gastrointestinal stromal tumors (GISTs) especially in children and in young adult patients whose disease does not harbour mutations on KIT and PDGFRA and are poorly responsive to conventional therapies. However, it is too early to reach conclusions on IGF1R as a novel therapeutic target in GIST because the receptor's biological role is still to be defined and the clinical significance in patients needs to be studied in larger studies. We update and comment the current literature on IGF1R in GISTs and discuss the future perspectives in this promising field

Identification of a novel quinoline-based DNA demethylating compound highly potent in cancer cells

Background DNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported in cancer initiation and progression. To date, two DNMT inhibitors (DNMTi), 5-azacytidine (5-AZA) and 5-aza-2′-deoxycytidine (DAC), are approved for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Nevertheless, they are chemically instable and quite toxic for healthy cells; thus, the discovery of novel DNMTi is urgent. Results Here, we report the identification of a new quinoline-based molecule, MC3353, as a non-nucleoside inhibitor and downregulator of DNMT. This compound was able, in promoter demethylating assays, to induce enhanced green fluorescence protein (EGFP) gene expression in HCT116 cells and transcription in a cytomegalovirus (CMV) promoter-driven luciferase reporter system in KG-1 cells. Moreover, MC3353 displayed a strong antiproliferative activity when tested on HCT116 colon cancer cells after 48 h of treatment at 0.5 μM. At higher doses, this compound provided a cytotoxic effect in double DNMT knockout HCT116 cells. MC3353 was also screened on a different panel of cancer cells (KG-1 and U-937 acute myeloid leukemia, RAJI Burkitts lymphoma, PC-3 prostate cancer, and MDA-MB-231 breast cancer), where it arrested cell proliferation and reduced viability after 48 h of treatment with IC50 values ranging from 0.3 to 0.9 μM. Compared to healthy cell models, MC3353 induced apoptosis (e.g., U-937 and KG-1 cells) or necrosis (e.g., RAJI cells) at lower concentrations. Importantly, together with the main DNMT3A enzyme inhibition, MC3353 was also able to downregulate the DNMT3A protein level in selected HCT116 and PC-3 cell lines. Additionally, this compound provided impairment of the epithelial-to-mesenchymal transition (EMT) by inducing E-cadherin while reducing matrix metalloproteinase (MMP2) mRNA and protein levels in PC-3 and HCT116 cells. Last, tested on a panel of primary osteosarcoma cell lines, MC3353 markedly inhibited cell growth with low single-digit micromolar IC50 ranging from 1.1 to 2.4 μM. Interestingly, in Saos-2 osteosarcoma cells, MC3353 induced both expression of genes and mineralized the matrix as evidence of osteosarcoma to osteoblast differentiation. Conclusions The present work describes MC3353 as a novel DNMTi displaying a stronger in cell demethylating ability than both 5-AZA and DAC, providing re-activation of the silenced ubiquitin C-terminal hydrolase L1 (UCHL1) gene. MC3353 displayed dose- and time-dependent antiproliferative activity in several cancer cell types, inducing cell death and affecting EMT through E-cadherin and MMP2 modulation. In addition, this compound proved efficacy even in primary osteosarcoma cell models, through the modulation of genes involved in osteoblast differentiation.This work was supported by COST Action CM1406 (PBA, LA, AM, SV); by Ricerca Finalizzata 2013 PE-2013-02355271 (AM); by PRIN 2016 (prot. 20152TE5PK) (AM, LA); by AIRC grants n. 19162 (AM), 17217 (LA), and 18843 (MT); by NIH funds n. R01GM114306 (AM) and BLUEPRINT n. 282510 (AM, LA); by Programma VALERE: Vanvitelli per la Ricerca (LA) and the Italian-Flag Project-EPIGEN (LA); and by Pasteur Institute-Cenci Bolognetti Foundation (MT). MS was supported by a Waxweiler grant for cancer prevention research from the Action Lions Vaincre le Cancer. CF is a recipient of a Télévie Luxembourg fellowship. The work at LBMCC was supported by the Recherche Cancer et Sang foundation, by the Recherches Scientifiques Luxembourg association, by the Een Häerz fir kriibskrank Kanner association, by the Action LIONS Vaincre le Cancer association, and by Télévie Luxembourg. MD was supported by the Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Korea; the Tumor Microenvironment GCRC (2011-0030001) from the National Research Foundation funded by the Ministry of Science and ICT of Korea; the Creative-Pioneering Researchers Program through Seoul National University (SNU) [Funding number: 370C-20160062]; and Brain Korea (BK) 21 Plus program, Korea

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool