Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-β1 has been identified as a key driving ...force behind metastatic breast cancer, with promising therapeutic implications.
Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1β, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort.
Our data show that asporin is a stroma-derived inhibitor of TGF-β1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy.
We present the combined NuSTAR and XMM-Newton 0.6-79 keV spectral analysis of a Seyfert 2 galaxy, NGC 1358, which we selected as a candidate Compton-thick (CT) active galactic nucleus (AGN) on the ...basis of previous Swift/BAT and Chandra studies. According to our analysis, NGC 1358 is confirmed to be a CT-AGN using physically motivated models, at >3 confidence level. Our best fit shows that the column density along the line of sight of the obscuring material surrounding the accreting supermassive black hole is NH = (1.96-2.80) × 1024 cm−2. The high-quality data from NuSTAR give the best constraints on the spectral shape above ∼10 keV to date on NGC 1358. Moreover, by combining NuSTAR and XMM-Newton data, we find that the obscuring torus has a low covering factor (fc < 0.17), and the obscuring material is distributed in clumps, rather than uniformly. We also derive an estimate of NGC 1358's Eddington ratio, finding it to be λEdd ∼ × 10−2, which is in acceptable agreement with previous measurements. Finally, we find no evidence of short-term variability, over a ∼100 ks time span, in terms of both line-of-sight column density and flux.
We present an updated catalogue of 113 X-ray flares detected by Swift in the ∼33 per cent of the X-ray afterglows of gamma-ray burst (GRB). 43 flares have a measured redshift. For the first time the ...analysis is performed in four different X-ray energy bands, allowing us to constrain the evolution of the flare temporal properties with energy. We find that flares are narrower at higher energies: their width follows a power-law relation w∝E−0.5 reminiscent of the prompt emission. Flares are asymmetric structures, with a decay time which is twice the rise time on average. Both time-scales linearly evolve with time, giving rise to a constant rise-to-decay ratio: this implies that both time-scales are stretched by the same factor. As a consequence, the flare width linearly evolves with time to larger values: this is a key point that clearly distinguishes the flare from the GRB prompt emission. The flare 0.3–10 keV peak luminosity decreases with time, following a power-law behaviour with large scatter: Lpk∝t−2.7±0.5pk. When multiple flares are present, a global softening trend is established: each flare is on average softer than the previous one. The 0.3–10 keV isotropic energy distribution is a lognormal peaked at 1051 erg, with a possible excess at low energies. The flare average spectral energy distribution is found to be a power law with spectral energy index β∼ 1.1. These results confirmed that the flares are tightly linked to the prompt emission. However, after considering various models we conclude that no model is currently able to account for the entire set of observations.
How the accreted mass settling on the surface of a neutron star affects the topology of the magnetic field and how the secular evolution of the binary system depends on the magnetic field change is ...still an open issue. We report evidence for a clear drop in the observed magnetic field in the accreting pulsar V0332+53 after undergoing a bright 3-month long X-ray outburst. We determine the field from the position of the fundamental cyclotron line in its X-ray spectrum and relate it to the luminosity. For equal levels of luminosity, in the declining phase we measure a systematically lower value of the cyclotron line energy with respect to the rising phase. This results in a drop of ∼1.7 × 1011 G of the observed field between the onset and the end of the outburst. The settling of the accreted plasma on to the polar cap seems to induce a distortion of the magnetic field lines weakening their intensity along the accretion columns. Therefore, the dissipation rate of the magnetic field could be much faster than previously estimated, unless the field is able to restore its original configuration on a time-scale comparable with the outbursts recurrence time.
Context.
The Cygnus Loop (G74.0-8.5) is a very well-known nearby supernova remnant (SNR) in our Galaxy. Thanks to its large size, brightness, and angular offset from the Galactic plane, it has been ...studied in detail from radio to
γ
-ray emission. The
γ
-rays probe the populations of energetic particles and their acceleration mechanisms at low shock speeds.
Aims.
We present an analysis of the
γ
-ray emission detected by the Large Area Telescope on board the
Fermi
Gamma-ray Space Telescope over 11 yr in the region of the Cygnus Loop.
Methods.
We performed detailed morphological and spectral studies of the
γ
-ray emission toward the remnant from 100 MeV to 100 GeV and compared it with X-ray, UV, optical, and radio images. The higher statistics with respect to the previous studies enabled us to decompose the emission from the remnant into two morphological components to model its nonthermal multiwavelength emission.
Results.
The extended
γ
-ray emission is well correlated with the thermal X-ray and UV emission of the SNR. Our morphological analysis reveals that a model considering two contributions from the X-ray and the UV emission regions is the best description of the
γ
-ray data. Both components show a curved spectrum, but the X-ray component is softer and more curved than the UV component, suggesting a different physical origin. The multiwavelength modeling of emission toward the SNR suggests that the nonthermal radio and
γ
-ray emission associated with the UV component is mostly due to the reacceleration of preexisting cosmic rays by radiative shocks in the adjacent clouds, while the nonthermal emission associated with the X-ray component arises from freshly accelerated cosmic rays.
We present the combined Chandra and Swift-BAT spectral analysis of seven Seyfert 2 galaxies selected from the Swift-BAT 100 month catalog. We selected nearby (z ≤ 0.03) sources lacking a ROSAT ...counterpart that never previously been observed with Chandra in the 0.3-10 keV energy range, and targeted these objects with 10 ks Chandra ACIS-S observations. The X-ray spectral fitting over the 0.3-150 keV energy range allows us to determine that all the objects are significantly obscured, with NH ≥ 1023 cm−2 at a >99% confidence level. Moreover, one to three sources are candidate Compton-thick Active Galactic Nuclei (CT-AGNs; i.e., NH ≥ 1024 cm−2). We also test the recent spectral curvature method developed by Koss et al. to find candidate CT-AGNs, finding a good agreement between our results and their predictions. Because the selection criteria we adopted were effective in detecting highly obscured AGNs, further observations of these and other Seyfert 2 galaxies selected from the Swift-BAT 100 month catalog will allow us to create a statistically significant sample of highly obscured AGNs, therefore providing a better understanding of the physics of the obscuration processes.
Introduction
According to the World Health Organization (WHO, 2017) depressive disorder continues to be the most widespread and growing mental illness in the world, also assumes that in 2020 ...depression will have a prevalence equal to one in six individuals. Studies of neuroanatomy have highlighted structural alterations in the hippocampus, striatal nuclei and prefrontal cortex in patients with mood disorders. This alteration in depressed patients is closely related to the secretion of neurotrophic factors, in particular there is a reduction in BDNF (Brain Derived Neurotrophic Factor).
Objectives
The objective of this study is to demonstrate which treatments are effective in reducing depressive symptoms that allow the increase of BDNF and consequently the structural homostaticity of the brain.
Methods
We have selected data from the literature of the last decade, collected on major search engines such as: Google Scholar, Research Gate, PubMed, Ebsco. Articles collected by selecting the following Keyword: depression, BDNF (Brain Derived Neurotrophic Factor), neuroimaging cognitive behavior therapy.
Results
The results show that in patients treated with a single drug treatment or vagus nerve stimulation, repetitive transcranial magnetic stimulation (Lang et al., 2008) or electroconvulsive therapy had improvements in BDNF levels, although compared to drug treatment there are problems of no responders, no compliance and lack of effectiveness in reducing vulnerability to relapse. In addition, the study has shown that patients treated with cognitive behavioral therapy have reported greater changes in the frontal and temporal cortex reducing both depressive symptoms and the risk of relapse.
Conclusions
Underlines the importance of an integrated approach
We use a nearly complete sample of gamma-ray bursts (GRBs) detected by the Swift satellite to study the correlations between the spectral peak energy E
peak of the prompt emission, the isotropic ...energetics E
iso and the isotropic luminosity L
iso. This GRB sample is characterized by a high level of completeness in redshift (90 per cent). This allows us to probe in an unbiased way the issue related to the physical origin of these correlations against selection effects. We find that one burst, GRB 061021, is an outlier to the E
peak-E
iso correlation. Despite this case, we find strong E
peak-E
iso and E
peak-L
iso correlations for the bursts of the complete sample. Their slopes, normalizations and dispersions are consistent with those found with the whole sample of bursts with measured redshift and E
peak. This means that the biases present in the total sample commonly used to study these correlations do not affect their properties. Finally, we also find no evolution with redshift of the E
peak-E
iso and E
peak-L
iso correlations.
Symbiotic star surveys have traditionally relied almost exclusively on low resolution optical spectroscopy. However, we can obtain a more reliable estimate of their total Galactic population by using ...all available signatures of the symbiotic phenomenon. Here we report the discovery of a hard X-ray source, 4PBC J0642.9+5528, in the Swift hard X-ray all-sky survey, and identify it with a poorly studied red giant, SU Lyn, using pointed Swift observations and ground-based optical spectroscopy. The X-ray spectrum, the optical to UV spectrum, and the rapid UV variability of SU Lyn are all consistent with our interpretation that it is a symbiotic star containing an accreting white dwarf. The symbiotic nature of SU Lyn went unnoticed until now, because it does not exhibit emission lines strong enough to be obvious in low resolution spectra. We argue that symbiotic stars without shell-burning have weak emission lines, and that the current lists of symbiotic stars are biased in favour of shell-burning systems. We conclude that the true population of symbiotic stars has been underestimated, potentially by a large factor.
ABSTRACT
Accretion and ejection of matter in active galactic nuclei (AGNs) are tightly connected phenomena and represent fundamental mechanisms regulating the growth of the central supermassive black ...hole and the evolution of the host galaxy. However, the exact physical processes involved are not yet fully understood. We present a high-resolution spectral analysis of a simultaneous XMM–Newton and NuSTAR observation of the narrow line Seyfert 1 (NLS1) AGN 1H 1934-063, during which the X-ray flux dropped by a factor of ∼6 and subsequently recovered within 140 kiloseconds. By means of the time-resolved and flux-resolved X-ray spectroscopy, we discover a potentially variable warm absorber and a relatively stable ultra-fast outflow (UFO, $v_\mathrm{UFO}\sim -0.075\, c$) with a mild ionization state ($\log (\xi /\mathrm{erg\, cm\, s^{-1})}\sim 1.6$). The detected emission lines (especially a strong and broad feature around 1 keV) are of unknown origin and cannot be explained with emission from plasmas in photo- or collisional-ionization equilibrium. Such emission lines could be well described by a strongly blueshifted (z ∼ −0.3) secondary reflection off the base of the equatorial outflows, which may reveal the link between the reprocessing of the inner accretion flow photons and the ejection. However, this scenario although being very promising is only tentative and will be tested with future observations.
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