Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells

Chemotherapy-induced interleukin-8 (IL-8) signaling reduces the sensitivity of prostate cancer cells to undergo apoptosis. In this study, we investigated how endogenous and drug-induced IL-8 signaling altered the extrinsic apoptosis pathway by determining the sensitivity of LNCaP and PC3 cells to administration of the death receptor agonist tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL induced concentration-dependent decreases in LNCaP and PC3 cell viability, coincident with increased levels of apoptosis and the potentiation of IL-8 secretion. Administration of recombinant human IL-8 was shown to increase the mRNA transcript levels and expression of c+FLIPL and c-FLIPS, two isoforms of the endogenous caspase-8 inhibitor. Pretreatment with the CXCR2 antagonist AZ10397767 significantly attenuated IL-8-induced c-FLIP mRNA up-regulation whereas inhibition of androgen receptor- and/or nuclear factor-kappa B-mediated transcription attenuated IL-8-induced c-FLIP expression in LNCaP and PC3 cells, respectively. Inhibition of c-FLIP expression was shown to induce spontaneous apoptosis in both cell lines and to sensitize these prostate cancer cells to treatment with TRAIL, oxaliplatin, and docetaxel. Coadministration of AZ10397767 also increased the sensitivity of PC3 cells to the apoptosis-inducing effects of recombinant TRAIL, most likely due to the ability of this antagonist to block TRAIL- and IL-8-induced up-regulation of c-FLIP in these cells. We conclude that endogenous and TRAIL-induced IL-8 signaling can modulate the extrinsic apoptosis pathway in prostate cancer cells through direct transcriptional regulation of c-FLIP. Therefore, targeted inhibition of IL-8 signaling or c-FLIP expression in prostate cancer may be an attractive therapeutic strategy to sensitize this stage of disease to chemotherapy.

Updated parameters for the transiting exoplanet WASP-3b using RISE, a new fast camera for the Liverpool Telescope

Some of the first results are reported from RISE - a new fast camera mounted on the Liverpool Telescope primarily designed to obtain high time-resolution light curves of transiting extrasolar planets for the purpose of transit timing. A full and partial transit of WASP-3 are presented, and a Markov-Chain Monte Carlo analysis is used to update the parameters from the discovery paper. This results in a planetary radius of 1.29(-0.12)(+0.05) R-J and therefore a density of 0.82(-0.09)(+0.14) rho(J), consistent with previous results. The inclination is 85.06(-0.15)(+0.16) deg, in agreement (but with a significant improvement in the precision) with the previously determined value. Central transit times are found to be consistent with the ephemeris given in the discovery paper; however, a new ephemeris calculated using the longer baseline results in T-c(0) = 2 454 605.55915 +/- 0.00023 HJD and P = 1.846835 +/- 0.000002 days.

On the evolutionary status of short-period cataclysmic variables

We present high-speed, three-colour photometry of seven short-period (Porb

GD 552: a cataclysmic variable with a brown dwarf companion?

GD 552 is a high proper motion star with the strong, double-peaked emission lines characteristic of the dwarf nova class of cataclysmic variable (CV) star, and yet no outburst has been detected during the past 12yr of monitoring. We present spectroscopy taken with the aim of detecting emission from the mass donor in this system. We fail to do so at a level which allows us to rule out the presence of a near-main-sequence star donor. Given GD 552's orbital period of 103 min, this suggests that it is either a system that has evolved through the ~80-minute orbital period minimum of CV stars and now has a brown dwarf mass donor, or that has formed with a brown dwarf donor in the first place. This model explains the low observed orbital velocity of the white dwarf and GD 552's low luminosity. It is also consistent with the absence of outbursts from the system.

Time-resolved optical photometry of the ultracompact binary 4U 0614+091

We present a detailed optical study of the ultracompact X-ray binary 4U 0614+091. We have used 63 hr of time-resolved optical photometry taken with three different telescopes (IAC80, NOT, and SPM) to search for optical modulations. The power spectra of each data set reveals sinusoidal modulations with different periods, which are not always present. The strongest modulation has a period of 51.3 minutes, a semiamplitude of 4.6 mmag, and is present in the IAC80 data. The SPM and NOT data show periods of 42 minutes and 64 minutes, respectively, but with much weaker amplitudes, 2.6 mmag and 1.3 mmag, respectively. These modulations arise from either X-ray irradiation of the inner face of the secondary star and/or a superhump modulation from the accretion disk, or quasiperiodic modulations in the accretion disk. It is unclear whether these periods/quasi-periodic modulations are related to the orbital period; however, the strongest period of 51.3 minutes is close to earlier tentative orbital periods. Further observations taken over a long baseline are encouraged.

The first polarimetric signatures of infrared jets in X-ray binaries

We present near-infrared linear spectropolarimetry of a sample of persistent X-ray binaries, Sco X-1, Cyg X-2, and GRS 1915+105. The slopes of the spectra are shallower than what is expected from a standard steady state accretion disk, and can be explained if the near-infrared flux contains a contribution from an optically thin jet. For the neutron star systems, Sco X-1 and Cyg X-2, the polarization levels at 2.4 mu m are 1.3% +/- 0.10% and 5.4% +/- 0.7%, respectively, which is greater than the polarization level at 1.65 mu m. This cannot be explained by interstellar polarization or electron scattering in the anisotropic environment of the accretion flow. We propose that the most likely explanation is that this is the polarimetric signature of synchrotron emission arising from close to the base of the jets in these systems. In the black hole system GRS 1915+105 the observed polarization, although high (5.0% +/- 1.2% at 2.4 mu m), may be consistent with interstellar polarization. For Sco X-1 the position angle of the radio jet on the sky is approximately perpendicular to the near-infrared position angle (electric vector), suggesting that the magnetic field is aligned with the jet. These observations may be a first step toward probing the ordering, alignment, and variability of the outflow magnetic field in a region closer to the central accreting object than is observed in the radio band.

A Planetary Nebula around Nova V458 Vulpeculae Undergoing Flash Ionization

Nova V458 Vul erupted on 2007 August 8 and reached a visual magnitude of 8.1 a few days later. Ha images obtained 6 weeks before the outburst as part of the IPHAS Galactic plane survey reveal an 18th magnitude progenitor surrounded by an extended nebula. Subsequent images and spectroscopy of the nebula reveal an inner nebular knot increasing rapidly in brightness due to flash ionization by the nova event. We derive a distance of 13 kpc based on light travel time considerations, which is supported by two other distance estimation methods. The nebula has an ionized mass of 0.2 Msolar and a low expansion velocity: this rules it out as ejecta from a previous nova eruption, and is consistent with it being a ~14,000 year old planetary nebula, probably the product of a prior common envelope (CE) phase of evolution of the binary system. The large derived distance means that the mass of the erupting WD component of the binary is high. We identify two possible evolutionary scenarios, in at least one of which the system is massive enough to produce a Type Ia supernova upon merging.

The VLT-FLAMES survey of massive stars: atmospheric parameters and rotational velocity distributions for B-type stars in the Magellanic Clouds (vol 457, pg 265, 2006)

We correct the estimates of the dispersions in the rotational velocities for early-type stars in our Galaxy (Dufton et al. 2006, A&A, 457, 265) and the Magellanic Clouds (Hunter et al. 2008, A&A, 479, 541). The corrected values are pi(1/4) (i.e. approximately 33%) larger than those published in the original papers.