The composition of the protoplanetary disc is thought to be linked to the composition of the host star, where a higher overall metallicity provides the building blocks for planets. However, most of ...the planet formation simulations only link the stellar iron abundance Fe/H to planet formation and the iron abundance in itself is used as a proxy to scale all elements. On the other hand, large surveys of stellar abundances show that this is not true. Here we use stellar abundances from the GALAH surveys to determine the average detailed abundances of Fe, Si, Mg, O, and C for a broad range of host star metallicities with Fe/H spanning from −0.4 to +0.4. Using an equilibrium chemical model that features the most important rock-forming compounds as well as volatile contributions of H
2
O, CO
2
, CH
4
, and CO, we calculate the chemical composition of solid planetary building blocks around stars with different metallicities. Solid building blocks that are formed entirely interior to the water ice line (
T
> 150 K) only show an increase in Mg
2
SiO
4
and a decrease in MgSiO
3
for increasing host star metallicity, which is related to the increase of Mg/Si for higher Fe/H. Solid planetary building blocks forming exterior to the water ice line (
T
< 150 K), on the other hand, show dramatic changes in their composition. In particular, the water ice content decreases from around ~50% at Fe/H = −0.4 to ~6% at Fe/H = 0.4 in our chemical model. This is mainly caused by the increasing C/O ratio with increasing Fe/H, which binds most of the oxygen in gaseous CO and CO
2
, resulting in a small water ice fraction. Planet formation simulations coupled with the chemical model confirm these results by showing that the water ice content of super-Earths decreases with increasing host star metallicity due to the increased C/O ratio. This decrease of the water ice fraction has important consequences for planet formation, planetary composition, and the eventual habitability of planetary systems formed around these high-metallicity stars.
Context. Elements heavier than Li are produced in the interiors of stars. However, for many elements the exact production sites and the timescales on which they are dispersed into the interstellar ...medium are unknown. Having a clear picture on the origins of the elements is important for our ability to trace and understand the formation and chemical evolution of the Milky Way and its stellar populations. Aims. The aim of this study is to investigate the origin and evolution of Sc, V, Mn, and Co for a homogeneous and statistically significant sample of stars probing the different populations of the Milky Way, in particular the thin and thick disks. Methods. Using high-resolution spectra obtained with the MIKE, FEROS, SOFIN, FIES, UVES, and HARPS spectrographs, we determine Sc, V, Mn, and Co abundances for a large sample of F and G dwarfs in the solar neighborhood. The method is based on spectral synthesis and using one-dimensional, plane-parallel, local thermodynamic equilibrium (LTE) model stellar atmospheres calculated with the MARCS 2012 code. The non-LTE (NLTE) corrections from the literature were applied to Mn and Co. Results. We find that the abundance trends derived for Sc (594 stars), V (466 stars), and Co (567 stars) are very similar to what has been observed for the α-elements in the thin and thick disks. On the contrary, Mn (569 stars) is generally underabundant relative to the Sun (i.e., Mn/Fe < 0) for Fe/H < 0. In addition, for Mn, when NLTE corrections are applied, the trend changes and is almost flat over the entire metallicity range of the stars in our sample (−2 ≲ Fe/H ≲ + 0.4). The Sc/Fe-Fe/H abundance trends show a small separation between the thin and thick disks, while for V and Co they completely overlap. For Mn there is a small difference in Mn/Fe, but only when NLTE corrections are used. Comparisons with Ti as a reference element show flat trends for all the elements except for Mn that show well separated Mn/Ti-Ti/H trends for the thin and thick disks. Conclusions. The elements Sc and V present trends compatible with production from type II supernovae (SNII) events. In addition, Sc clearly shows a metallicity dependence for Fe/H < −1. Instead, Mn is produced in SNII events for Fe/H ≲ −0.4 and then type Ia supernovae start to produce Mn. Finally, Co appears to be produced mainly in SNII with suggestion of enrichment from hypernovae at low metallicities.
Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy worldwide due to a late diagnosis caused by the lack of specific symptoms and rapid dissemination into the peritoneal ...cavity. The standard of care for OC treatment is surgical cytoreduction followed by platinum-based chemotherapy. While a response to this frontline treatment is common, most patients undergo relapse within 2 years and frequently develop a chemoresistant disease that has become unresponsive to standard treatments. Moreover, also due to the lack of actionable mutations, very few alternative therapeutic strategies have been designed as yet for the treatment of recurrent OC. This dismal clinical perspective raises the need for pre-clinical models that faithfully recapitulate the original disease and therefore offer suitable tools to design novel therapeutic approaches. In this regard, patient-derived models are endowed with high translational relevance, as they can better capture specific aspects of OC such as (i) the high inter- and intra-tumor heterogeneity, (ii) the role of cancer stem cells (a small subset of tumor cells endowed with tumor-initiating ability, which can sustain tumor spreading, recurrence and chemoresistance), and (iii) the involvement of the tumor microenvironment, which interacts with tumor cells and modulates their behavior. This review describes the different in vitro patient-derived models that have been developed in recent years in the field of OC research, focusing on their ability to recapitulate specific features of this disease. We also discuss the possibilities of leveraging such models as personalized platforms to design new therapeutic approaches and guide clinical decisions.
The Milky Way is a unique laboratory in which stellar properties can be measured and analyzed in detail. In particular, stars in the older populations encode information on the mechanisms that led to ...the formation of our Galaxy. In this article, we analyze the kinematics, spatial distribution, and chemistry of a large number of stars in the solar neighborhood, where all of the main Galactic components are well represented. We find that the thick disk comprises two distinct and overlapping stellar populations with different kinematic properties and chemical compositions. The metal-weak thick disk (MWTD) contains two-times less metal content than the canonical thick disk, and exhibits enrichment of light elements typical of the oldest stellar populations of the Galaxy. The rotational velocity of the MWTD around the Galactic center is ∼150 km s−1, corresponding to a rotational lag of 30 km s−1 relative to the canonical thick disk (∼180 km s−1), with a velocity dispersion of 60 km s−1. This stellar population likely originated from the merger of a dwarf galaxy during the early phases of our Galaxy's assembly, or it is a precursor disk, formed in the inner Galaxy and brought into the solar neighborhood by bar instability or spiral-arm formation mechanisms.
Context. Elements heavier than iron are produced through neutron-capture processes in the different phases of stellar evolution. Asymptotic giant branch (AGB) stars are believed to be mainly ...responsible for elements that form through the slow neutron-capture process, while the elements created in the rapid neutron-capture process have production sites that are less understood. Knowledge of abundance ratios as functions of metallicity can lead to insight into the origin and evolution of our Galaxy and its stellar populations. Aims. We aim to trace the chemical evolution of the neutron-capture elements Sr, Zr, La, Ce, Nd, Sm, and Eu in the Milky Way stellar disk. This will allow us to constrain the formation sites of these elements, as well as to probe the evolution of the Galactic thin and thick disks. Methods. Using spectra of high resolution (42 000 ≲ R ≲ 65 000) and high signal-to-noise (S/N ≳ 200) obtained with the MIKE and the FEROS spectrographs, we determine Sr, Zr, La, Ce, Nd, Sm, and Eu abundances for a sample of 593 F and G dwarf stars in the solar neighborhood. The abundance analysis is based on spectral synthesis using one-dimensional, plane-parallel, local thermodynamic equilibrium (LTE) model stellar atmospheres calculated with the MARCS 2012 code. Results. We present abundance results for Sr (156 stars), Zr (311 stars), La (242 stars), Ce (365 stars), Nd (395 stars), Sm (280 stars), and Eu (378 stars). We find that Nd, Sm, and Eu show trends similar to what is observed for the α elements in the X/Fe–Fe/H abundance plane. For Sr/Fe and Zr/Fe, we find decreasing abundance ratios for increasing metallicity, reaching sub-solar values at super-solar metallicities. La/Fe and Ce/Fe do not show any clear trend with metallicity, and they are close to solar values at all Fe/H. The trends of abundance ratios X/Fe as a function of stellar ages present different slopes before and after 8 Gyr. Conclusions. The rapid neutron-capture process is active early in the Galaxy, mainly in type-II supernovae from stars in the mass range 8−10 M⊙. Europium is almost completely produced by the r-process, but Nd and Sm show similar trends to Eu even if their s-process component is higher. Strontium and Zr are thought to be mainly produced by the s-process, but show significant enrichment at low metallicity that requires extra r-process production, which probably is different from the classical r-process. Finally, La and Ce are mainly produced via s-process from AGB stars in the mass range 2−4 M⊙, which can be seen by the decrease in La/Eu and Ce/Eu at Fe/H ≈ −0.5. The trend of X/Fe with age could be explained by considering that the decrease in X/Fe for the thick disk stars can be due to the decrease in type-II supernovae with time, meaning a reduced enrichment of r-process elements in the interstellar medium. In the thin disk, the trends are flatter, which is probably due to the main production from the s-process being balanced by Fe production from type-Ia supernovae.
Neuropilins are a class of cell surface proteins implicated in cell migration and angiogenesis, with aberrant expression in human tumors. Here, we show that the expression of Neuropilin-2 (NRP2) ...controls EGFR protein levels, thereby impinging on intracellular signaling, viability, and response to targeted therapies of oncogene-addicted cells. Notably, increased NRP2 expression in EGFR-addicted tumor cells led to downregulation of EGFR protein and tumor cell growth inhibition. NRP2 also blunted upregulation of an EGFR "rescue" pathway induced by targeted therapy in Met-addicted carcinoma cells. Cancer cells acquiring resistance to MET oncogene-targeted drugs invariably underwent NRP2 loss, a step required for EGFR upregulation. Mechanistic investigations revealed that NRP2 loss activated NFkB and upregulated the EGFR-associated protein KIAA1199/CEMIP, which is known to oppose the degradation of activated EGFR kinase. Notably, KIAA1199 silencing in oncogene-addicted tumor cells improved therapeutic responses and counteracted acquired drug resistance. Our findings define NRP2 as the pivotal switch of a novel broad-acting and actionable pathway controlling EGFR signaling, and driving resistance to therapies targeting oncogene-addiction.
These important findings identify the cell surface molecule Nrp2 as the pivotal switch of a novel, actionable pathway driving EGFR upregulation and resistance to oncogene- targeted therapies.
.
Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non ...neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining.
Cancer stem cells (CSC) have been implicated in tumor progression. In ovarian carcinoma (OC), CSC drive tumor formation, dissemination and recurrence, as well as drug resistance, thus contributing to ...the high death-to-incidence ratio of this disease. However, the molecular basis of such a pathogenic role of ovarian CSC (OCSC) has been elucidated only to a limited extent. In this context, the functional contribution of the L1 cell adhesion molecule (L1CAM) to OC stemness remains elusive.
The expression of L1CAM was investigated in patient-derived OCSC. The genetic manipulation of L1CAM in OC cells provided gain and loss-of-function models that were then employed in cell biological assays as well as in vivo tumorigenesis experiments to assess the role of L1CAM in OC cell stemness and in OCSC-driven tumor initiation. We applied antibody-mediated neutralization to investigate L1CAM druggability. Biochemical approaches were then combined with functional in vitro assays to study the molecular mechanisms underlying the functional role of L1CAM in OCSC.
We report that L1CAM is upregulated in patient-derived OCSC. Functional studies showed that L1CAM promotes several stemness-related properties in OC cells, including sphere formation, tumor initiation and chemoresistance. These activities were repressed by an L1CAM-neutralizing antibody, pointing to L1CAM as a druggable target. Mechanistically, L1CAM interacted with and activated fibroblast growth factor receptor-1 (FGFR1), which in turn induced the SRC-mediated activation of STAT3. The inhibition of STAT3 prevented L1CAM-dependent OC stemness and tumor initiation.
Our study implicate L1CAM in the tumorigenic function of OCSC and point to the L1CAM/FGFR1/SRC/STAT3 signaling pathway as a novel driver of OC stemness. We also provide evidence that targeting this pathway can contribute to OC eradication.
Background: Clinical and scientific evidence has shown that a range of long-lasting symptoms can persist in the post-virological period. However, little is known about the psychological sequelae of ...patients hospitalized for coronavirus disease 2019 (COVID-19).
Objective: This study aims to assess the prevalence of anxiety-depressive symptoms, post-traumatic stress disorder (PTSD), and post-traumatic growth among patients hospitalized for COVID-19 during the first wave of the pandemic 6 months after discharge, and to identify sociodemographic and clinical factors associated with psychological outcomes.
Method: This cross-sectional cohort study enrolled recovered COVID-19 patients during a multidisciplinary follow-up screening. At 6 months post-discharge, participants underwent a remote assessment with the Mini-International Neuropsychiatric Interview Plus and completed the Hospital Anxiety and Depression Scale, PTSD Checklist for DSM-5, and Post-Traumatic Growth Inventory. Descriptive and regression analyses were conducted.
Results: The sample was composed of 100 patients, mainly males (72%), with a mean ± SD age of 58.7 ± 11.8 years. Regarding psychological symptoms, 34% and 24% of patients, respectively, reported anxiety and depression over the clinical threshold, and 20% met the criteria for a possible PTSD diagnosis. Psychological symptoms were associated with the presence of a mood disorder in the patient's clinical history and having received a psychological consultation after discharge. Post-traumatic growth was associated with younger age and having received a psychological consultation after discharge.
Conclusions: A high prevalence of anxiety and depressive symptoms, potentially indicative for a mood or anxiety disorder, and PTSD was confirmed among COVID-19 survivors after 6 months. Anxiety and depressive symptoms and PTSD were associated with a previous diagnosis of a mood disorder and having received psychological consultation. Post-traumatic growth was associated with younger age and having received psychological consultation. Tailored psychological interventions could help to elaborate the psychological suffering and foster post-traumatic growth after a traumatic experience such as COVID-19 hospitalization.
A high prevalence of psychological symptoms has been observed among COVID-19 survivors 6 months after hospitalization.
Tailored psychological interventions could help to contain the psychological sequelae and facilitate post-traumatic growth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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