X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

The LOFT mission concept: a status update

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, >8m2 effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission

Targeting Endothelial Cell Metabolism by Inhibition of Pyruvate Dehydrogenase Kinase and Glutaminase-1.

Targeting endothelial cell (EC) metabolism should impair angiogenesis, regardless of how many angiogenic signals are present. The dependency of proliferating ECs on glucose and glutamine for energy and biomass production opens new opportunities for anti-angiogenic therapy in cancer. The aim of the present study was to investigate the role of pyruvate dehydrogenase kinase (PDK) inhibition with dichloroacetate (DCA), alone or in combination with the glutaminase-1 (GLS-1) inhibitor, Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES), on Human umbilical vein endothelial cells (HUVECs) metabolism, proliferation, apoptosis, migration, and vessel formation. We demonstrated that both drugs normalize HUVECs metabolism by decreasing glycolysis for DCA and by reducing glutamate production for BPTES. DCA and BPTES reduced HUVECs proliferation and migration but have no impact on tube formation. While DCA increased HUVECs respiration, BPTES decreased it. Using both drugs in combination further reduced HUVECs proliferation while normalizing respiration and apoptosis induction. Overall, we demonstrated that DCA, a metabolic drug under study to target cancer cells metabolism, also affects tumor angiogenesis. Combining DCA and BPTES may reduce adverse effect of each drug alone and favor tumor angiogenesis normalization

MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice.

In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitochondrial DNA (mtDNA) was sequenced. In a bottom-up approach, matched glycolytic and oxidative SQD9 cells were generated using FACS-sorting, and tested for their radiosensitivity/radioresistance. We found that acquired radioresistance is associated with a shift from a glycolytic to a more oxidative metabolism in SQD9 cells. The opposite was also true, as the most oxidative fraction isolated from SQD9 wild-type cells was also more radioresistant than the most glycolytic fraction. However, neither reduced hexokinase expression nor OXPHOS were directly responsible for the radioresistant phenotype. Radiosensitive and radioresistant cells had similar proliferation rates and were equally efficient for ATP production. They were equally sensitive to redox stress and had similar DNA damage repair, but radioresistant cells had an increased number of mitochondria and a higher mtDNA content. Thus, an oxidative switch is associated with but is not responsible for acquired radioresistance in human SQD9 cells. In radioresistant cells, more abundant and fitter mitochondria could help to preserve mitochondrial functions upon irradiation

MitoQ Inhibits Human Breast Cancer Cell Migration, Invasion and Clonogenicity.

To successfully generate distant metastases, metastatic progenitor cells must simultaneously possess mesenchymal characteristics, resist to anoïkis, migrate and invade directionally, resist to redox and shear stresses in the systemic circulation, and possess stem cell characteristics. These cells primarily originate from metabolically hostile areas of the primary tumor, where oxygen and nutrient deprivation, together with metabolic waste accumulation, exert a strong selection pressure promoting evasion. Here, we followed the hypothesis according to which metastasis as a whole implies the existence of metabolic sensors. Among others, mitochondria are singled out as a major source of superoxide that supports the metastatic phenotype. Molecularly, stressed cancer cells increase mitochondrial superoxide production, which activates the transforming growth factor-β pathway through src directly within mitochondria, ultimately activating focal adhesion kinase Pyk2. The existence of mitochondria-targeted antioxidants constitutes an opportunity to interfere with the metastatic process. Here, using aggressive triple-negative and HER2-positive human breast cancer cell lines as models, we report that MitoQ inhibits all the metastatic traits that we tested in vitro. Compared to other mitochondria-targeted antioxidants, MitoQ already successfully passed Phase I safety clinical trials, which provides an important incentive for future preclinical and clinical evaluations of this drug for the prevention of breast cancer metastasis

Cell therapy for Parkinson's disease: A translational approach to assess the role of local and systemic immunosuppression

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases. However, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation and differentiation. Parkinsonian primates received wild-type or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 months. Recovery was associated with restoration of dopaminergic activity detected both by PET imaging and histological examination. Local infiltration by T-cells and CD80/86-positive microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that, in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T-cell costimulation. This article is protected by copyright. All rights reserved

VizieR Online Data Catalog: UV/optical/NIR photometry for Type Ibn SNe (Pastorello+, 2015)

We started our optical and near-infrared (NIR) observational campaigns soon after the classification announcements of the two SNe, using the instruments available to our collaboration (see Tables A3 and A4). Additional photometry with small-size telescopes was kindly provided by amateur astronomers. Both SNe 2010al and 2011hw were visible for only 60-70 d after their discoveries, then they disappeared behind the Sun. We tried to recover SN 2010al at very late phases, but it was only visible in NIR observations obtained with the 8.4-m Large Binocular Telescope (Mt. Graham, Arizona; USA) equipped with Lucifer. Additional space observations of SNe 2010al and 2011hw in the ultra-violet (UV) and optical bands were obtained with the Swift satellite and its Ultraviolet/Optical Telescope (UVOT). These data were useful to constrain the large energy contribution of the UV domain in the early phases of the evolution of the two SNe. (3 data files)

SN 2013ej IN M74: A LUMINOUS AND FAST-DECLINING TYPE II-P SUPERNOVA

We present extensive ultraviolet, optical, and near-infrared observations of the type IIP supernova (SN IIP) 2013ej in the nearby spiral galaxy M74. The multicolor light curves, spanning from $\sim$ 8--185 days after explosion, show that it has a higher peak luminosity (i.e., M$_{V}$ $\sim$$-$17.83 mag at maximum light), a faster post-peak decline, and a shorter plateau phase (i.e., $\sim$ 50 days) compared to the normal type IIP SN 1999em. The mass of $^{56}$Ni is estimated as 0.02$\pm$0.01 M$_{\odot}$ from the radioactive tail of the bolometric light curve. The spectral evolution of SN 2013ej is similar to that of SN 2004et and SN 2007od, but shows a larger expansion velocity (i.e., $v_{Fe II} \sim$ 4600 km s$^{-1}$ at t $\sim$ 50 days) and broader line profiles. In the nebular phase, the emission of H$\alpha$ line displays a double-peak structure, perhaps due to the asymmetric distribution of $^{56}$Ni produced in the explosion. With the constraints from the main observables such as bolometric light curve, expansion velocity and photospheric temperature of SN 2013ej, we performed hydrodynamical simulations of the explosion parameters, yielding the total explosion energy as $\sim$0.7$\times$ 10$^{51}$ erg, the radius of the progenitor as $\sim$600 R$_{\odot}$, and the ejected mass as $\sim$10.6 M$_{\odot}$. These results suggest that SN 2013ej likely arose from a red supergiant with a mass of 12--13 M$_{\odot}$ immediately before the explosion.Comment: 32 pages, 11 figures, 6 tables. Accepted for publication in Ap