Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells

Epidemiological data indicate that the daily consumption of extra‑virgin olive oil (EVOO), a common dietary habit of the Mediterranean area, lowers the incidence of certain types of cancer, in particular bladder neoplasm. The aim of the present study was to evaluate the antiproliferative activity of polyphenols extracted from EVOO on bladder cancer (BCa), and to clarify the biological mechanisms that trigger cell death. Furthermore, we also evaluated the ability of low doses of extra‑virgin olive oil extract (EVOOE) to modulate the in vitro activity of paclitaxel or mitomycin, two antineoplastic drugs used in the management of different types of cancer. Our results showed that EVOOE significantly inhibited the proliferation and clonogenic ability of T24 and 5637 BCa cells in a dose‑dependent manner. Furthermore, cell cycle analysis after EVOOE treatment showed a marked growth arrest prior to mitosis in the G2/M phase for both cell lines, with the subsequent induction of apoptosis only in the T24 cells. Notably, simultaneous treatment of mitomycin C and EVOOE reduced the drug cytotoxicity due to inhibition of ROS production. Conversely, the co‑treatment of T24 cells with paclitaxel and the polyphenol extract strongly increased the apoptotic cell death at each tested concentration compared to paclitaxel alone. Our results support the epidemiological evidence indicating that olive oil consumption exerts health benefits and may represent a starting point for the development of new anticancer strategies

The birth of the gravitational-wave astronomy

Last years marked the beginning of a new era of observations of the Universe. Gravitational waves were detected from a binary black-hole merger by the Advanced LIGO detectors. Simultaneously, LISA Pathfinder demonstrated the technology for gravitational-wave observation in space beyond its planned requirements. Many gravitational observations and discoveries are expected in the next years with the Advanced LIGO and Virgo detectors, with strong impact on various astrophysical fields, from the physics governing compact object formation and evolution to the physics of the emission process and to nuclear astrophysics. I summarize here some historical milestones that led to the first detection and report the perspectives of the field. I also discuss the importance of the so-called multimessenger astronomy in which gravitational-wave sources will be observed in all bands of the electromagnetic spectrum with ground and space observatories and with neutrino telescopes

Detectors

Gravitationally coupled scalar fields, originally introduced by Jordan, Brans and Dicke to account for a non-constant gravitational coupling, are a prediction of many non-Einsteinian theories of gravity not excluding perturbative formulations of string theory. In this paper, we compute the cross sections for scattering and absorption of scalar and tensor gravitational waves by a resonant-mass detector in the framework of the Jordan-Brans-Dicke theory. The results are then specialized to the case of a detector of spherical shape and shown to reproduce those obtained in general relativity in a certain limit. Eventually we discuss the potential detectability of scalar waves emitted in a spherically symmetric gravitational collapse

Measurement of the thermal expansion coefficient of an Al-Mg alloy at ultra-low temperatures

We describe a result coming from an experiment based on an Al-Mg alloy (~ 5% Mg) suspended bar hit by an electron beam and operated above and below the termperature of transition from superconducting to normal state of the material. The amplitude of the bar first longitudinal mode of oscillation, excited by the beam interacting with the bulk, and the energy deposited by the beam in the bar are the quantities measured by the experiment. These quantities, inserted in the equations describing the mechanism of the mode excitation and complemented by an independent measurement of the specific heat, allow us to determine the linear expansion coefficient of the material.Comment: 13 pages, 4 figure

Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic hepatitis C virus infection

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper-1-like signature program in chronic (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection

Heme oxygenase-1 posttranslational modifications in the brain of subjects with Alzheimer disease and mild cognitive impairment. Free Radic.

a b s t r a c t Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Oxidative and nitrosative stress plays a principal role in the pathogenesis of AD. The induction of the heme oxygenase-1/biliverdin reductase-A (HO-1/BVR-A) system in the brain represents one of the earliest mechanisms activated by cells to counteract the noxious effects of increased reactive oxygen species and reactive nitrogen species. Although initially proposed as a neuroprotective system in AD brain, the HO-1/BVR-A pathophysiological features are under debate. We previously reported alterations in BVR activity along with decreased phosphorylation and increased oxidative/nitrosative posttranslational modifications in the brain of subjects with AD and those with mild cognitive impairment (MCI). Furthermore, other groups proposed the observed increase in HO-1 in AD brain as a possible neurotoxic mechanism. Here we provide new insights about HO-1 in the brain of subjects with AD and MCI, the latter condition being the transitional phase between normal aging and early AD. HO-1 protein levels were significantly increased in the hippocampus of AD subjects, whereas HO-2 protein levels were significantly decreased in both AD and MCI hippocampi. In addition, significant increases in Ser-residue phosphorylation together with increased oxidative posttranslational modifications were found in the hippocampus of AD subjects. Interestingly, despite the lack of oxidative stressinduced AD neuropathology in cerebellum, HO-1 demonstrated increased Ser-residue phosphorylation and oxidative posttranslational modifications in this brain area, suggesting HO-1 as a target of oxidative damage even in the cerebellum. The significance of these findings is profound and opens new avenues into the comprehension of the role of HO-1 in the pathogenesis of AD. & 2012 Elsevier Inc. All rights reserved. Introduction Increased oxidative and nitrosative stress represents one of the main mechanisms involved in the pathogenesis of neurodegenerative disorders such as Alzheimer disease (AD), which exhibits a large impairment of neuronal structure and molecular pathways due to oxidative stress-induced posttranslational modifications on both proteins and lipids AD is an age-related neurodegenerative disorder characterized histopathologically by the presence of senile plaques, neurofibrillary tangles (NFTs), and synapse loss in selected brain region

On the possible sources of gravitational wave bursts detectable today

We discuss the possibility that galactic gravitational wave sources might give burst signals at a rate of several events per year, detectable by state-of-the-art detectors. We are stimulated by the results of the data collected by the EXPLORER and NAUTILUS bar detectors in the 2001 run, which suggest an excess of coincidences between the two detectors, when the resonant bars are orthogonal to the galactic plane. Signals due to the coalescence of galactic compact binaries fulfill the energy requirements but are problematic for lack of known candidates with the necessary merging rate. We examine the limits imposed by galactic dynamics on the mass loss of the Galaxy due to GW emission, and we use them to put constraints also on the GW radiation from exotic objects, like binaries made of primordial black holes. We discuss the possibility that the events are due to GW bursts coming repeatedly from a single or a few compact sources. We examine different possible realizations of this idea, such as accreting neutron stars, strange quark stars, and the highly magnetized neutron stars (``magnetars'') introduced to explain Soft Gamma Repeaters. Various possibilities are excluded or appear very unlikely, while others at present cannot be excluded.Comment: 24 pages, 20 figure

Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey

Objective: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. Methods: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. Results: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). Discussion: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario

Lunar Gravitational-Wave Antenna

Monitoring of vibrational eigenmodes of an elastic body excited by gravitational waves was one of the first concepts proposed for the detection of gravitational waves. At laboratory scale, these experiments became known as resonant-bar detectors first developed by Joseph Weber in the 1960s. Due to the dimensions of these bars, the targeted signal frequencies were in the kHz range. Weber also pointed out that monitoring of vibrations of Earth or Moon could reveal gravitational waves in the mHz band. His Lunar Surface Gravimeter experiment deployed on the Moon by the Apollo 17 crew had a technical failure rendering the data useless. In this article, we revisit the idea and propose a Lunar Gravitational-Wave Antenna (LGWA). We find that LGWA could become an important partner observatory for joint observations with the space-borne, laser-interferometric detector LISA, and at the same time contribute an independent science case due to LGWA's unique features. Technical challenges need to be overcome for the deployment of the experiment, and development of inertial vibration sensor technology lays out a future path for this exciting detector concept.Comment: 29 pages, 17 figure