Mechanism of leptin expression in breast cancer cells: role of hypoxia-inducible factor-1alpha.

We reported previously that the obesity hormone leptin is overexpressed in breast cancer biopsies. Here, we investigated molecular mechanisms involved in this process, focusing on conditions that are associated with obesity, that is, hyperinsulinemia and induction of hypoxia. By using quantitative real-time PCR, immunofluorescent detection of proteins and enzyme-linked immunosorbent assays, we found that treatment of MCF-7 breast cancer cells with high doses of insulin or the hypoxia-mimetic agent CoCl2, or culturing the cells under hypoxic conditions significantly increased the expression of leptin mRNA and protein. Notably, the greatest leptin mRNA and protein expression were observed under combined hyperinsulinemia and hypoxia or hypoxia-mimetic treatments. Luciferase reporter assays suggested that increased leptin synthesis could be related to the activation of the leptin gene promoter. DNA affinity precipitation and chromatin immunoprecipitation experiments revealed that insulin, CoCl2 and/or hypoxia treatments augmented nuclear accumulation of hypoxia-inducible factor-1a (HIF-1a) and increased its interaction with several upstream leptin regulatory sequences, especially with the proximal promoter containing four hypoxia-response elements and three GC-rich regions. By using reverse chromatin precipitation, we determined that loading of HIF-1a on the proximal leptin promoter concurred with the recruitment of p300, the major HIF coactivator, suggesting that the HIF/p300 complex is involved in leptin transcription. The importance of HIF-1a in insulin- and CoCl2-activated leptin mRNA and protein expression was confirmed using RNA interferenc

Gpr investigation at the archaeological site of le cesine, lecce, italy

In this contribution, we present some results achieved in the archaeological site of Le Cesine, close to Lecce, in southern Italy. The investigations have been performed in a site close to the Adriatic Sea, only slightly explored up to now, and where the presence of an ancient Roman harbour is alleged on the basis of remains visible above all under the current sea level. This measurement campaign has been performed in the framework of a short-term scientific mission (STSM) performed in the framework of the European Cost Action 17131 (acronym SAGA), and has been aimed to identify possible points where future localized excavation might and hopefully will be performed in the next few years. Both a traditional elaboration and an innovative data processing based on a linear inverse scattering model have been performed on the data

Resolving the Radio Source Background: Deeper Understanding Through Confusion

We used the Karl G. Jansky Very Large Array (VLA) to image one primary beam area at 3 GHz with 8 arcsec FWHM resolution and 1.0 microJy/beam rms noise near the pointing center. The P(D) distribution from the central 10 arcmin of this confusion-limited image constrains the count of discrete sources in the 1 < S(microJy/beam) < 10 range. At this level the brightness-weighted differential count S^2 n(S) is converging rapidly, as predicted by evolutionary models in which the faintest radio sources are star-forming galaxies; and ~96$% of the background originating in galaxies has been resolved into discrete sources. About 63% of the radio background is produced by AGNs, and the remaining 37% comes from star-forming galaxies that obey the far-infrared (FIR) / radio correlation and account for most of the FIR background at lambda = 160 microns. Our new data confirm that radio sources powered by AGNs and star formation evolve at about the same rate, a result consistent with AGN feedback and the rough correlation of black hole and bulge stellar masses. The confusion at centimeter wavelengths is low enough that neither the planned SKA nor its pathfinder ASKAP EMU survey should be confusion limited, and the ultimate source detection limit imposed by "natural" confusion is < 0.01 microJy at 1.4 GHz. If discrete sources dominate the bright extragalactic background reported by ARCADE2 at 3.3 GHz, they cannot be located in or near galaxies and most are < 0.03 microJy at 1.4 GHz.Comment: 28 pages including 16 figures. ApJ accepted for publicatio

Direct peroral cholangioscopy in the management of difficult biliary stones: a new tool to confirm common bile duct clearance. Results of a preliminary study

Background and aims: Endoscopic sphincterotomy (ES) with stone extraction is the standard treatment for choledocholithiasis. After stone retrieval, balloon-occluded cholangiography is generally performed to confirm bile duct clearance but can miss residual stones particularly in patients with residual small-sized stones, a large bile duct or pneumobilia. In addition, difficult common bile duct (CBD) stones requiring advanced endoscopic techniques for retrieval are a potential risk factor for choledocholithiasis recurrence. Methods: We performed a retrospective evaluation of a prospectively maintained procedures database. From July 2016 to December 2017, all patients with difficult CBD stones who underwent endoscopic retrograde cholangiopancreatography (ERCP) with papillary balloon dilation-assisted stone retrieval and subsequent direct per-oral cholangioscopy (DPOC) using standard gastroscopes to confirm CBD clearance were analyzed. Results: Thirty-six patients who underwent ERCP and DPOC were included. Technical success, defined as deep intubation of CBD with hepatic hilum visualization, was achieved in 31 of 36 patients (86%). During DPOC, residual CBD stones were visualized and removed in 7 of 31 patients (22.5%). After a mean of 241 +/- 56 days of follow-up post-DPOC, no serious adverse events were reported, and there was no evidence or suspicion of recurrent choledocholithiasis. Conclusions: Direct per-oral cholangioscopy immediately following difficult CBD stone removal was safe, feasible and accurate. In this setting, DPOC at the time of ERCP appears to be a very useful tool to achieve complete clearance of choledocholithiasis.info:eu-repo/semantics/publishedVersio

On the detectability of gravitational waves background produced by gamma ray bursts

In this paper we discuss a new strategy for the detection of gravitational radiation likely emitted by cosmological gamma ray burst. Robust and conservative estimates lead to the conclusion that the uncorrelated superimposition of bursts of gravitational waves can be detected by interferometric detectors like VIRGO or LIGO. The expected signal is predicted to carry two very distinctive signatures: the cosmological dipole anisotropy and a characteristic time scale in the auto correlation spectrum, which might be exploited, perhaps with ad hoc modifications and/or upgrading of the planned experiments, to confirm the non-instrumental origin of the signal.Comment: 9 pages, 2 figures, LATEX2e, Accepted for pubblications as a Letter to the Editor in Journal of Physics G: Nuclear and Particle Physic

Cosmic Ray Protons and Magnetic Fields in Clusters of Galaxies and their Cosmological Consequences

The masses of clusters of galaxies estimated by gravitational lensing exceed in many cases the mass estimates based on hydrostatic equilibrium. This may suggest the existence of nonthermal pressure. We ask if radio galaxies can heat and support the cluster gas with injected cosmic ray protons and magnetic field densities, which are permitted by Faraday rotation and gamma ray observations of clusters of galaxies. We conclude that they are powerful enough to do this within a cluster radius of roughly 1 Mpc. If present, nonthermal pressures could lead to a revised estimate of the ratio of baryonic mass to total mass, and the apparent baryonic overdensity in clusters would disappear. In consequence, $\Omega_{\rm cold}$, the clumping part of the cosmological density $\Omega_{o}$, would be larger than $0.4\,h_{50}^{-1/2}$.Comment: Accepted by ApJ, 16 pages, LaTeX, 2 figures, epsfig.sty, aaspp4.st

Three-flavor atmospheric neutrino anomaly

We investigate the indications of flavor oscillations that come from the anomalous flavor composition of the atmospheric neutrino flux observed in some underground experiments. We study the information coming from the neutrino-induced $\mu$-like and $e$-like events both in the sub-GeV energy range (Kamiokande, IMB, Fr{\'e}jus, and NUSEX experiments) and in the multi-GeV energy range (Kamiokande experiment). First we analyze all the data in the limits of pure $\nu_\mu\leftrightarrow\nu_\tau$ and $\nu_\mu\leftrightarrow\nu_e$ oscillations. We obtain that $\nu_\mu\leftrightarrow\nu_e$ oscillations provide a better fit, in particular to the multi-GeV data. Then we perform a three-flavor analysis in the hypothesis of dominance of one neutrino square mass difference, $m^2$, implying that the neutrino mixing is parametrized by two angles, $(\psi,\,\phi)\in[0,\,\pi/2]$. We explore the space $(m^2,\,\psi,\,\phi)$ exhaustively, and find the regions favored by the oscillation hypothesis. The results are displayed in a form suited to the comparison with other flavor oscillation searches at accelerator, reactor, and solar $\nu$ experiments. In the analysis, we pay particular attention to the earth matter effects, to the correlation of the uncertainties, and to the symmetry properties of the oscillation probability.Comment: 25 pages (RevTeX) + 12 figures, requires epsfig.sty. All the figures are bitmapped. Postscript figures with full resolution are available at ftp://ftp.sns.ias.edu/pub/lisi/atmpaper