Association of LETM1 and MRPL36 Contributes to the Regulation of Mitochondrial ATP Production and Necrotic Cell Death

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome, and was deleted in nearly all patients with the syndrome. LETM1 encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. Here, we describe LETM1-mediated regulation of mitochondrial ATP production and biogenesis. We show that LETM1 overexpression can induce necrotic cell death in HeLa cells, in which LETM1 reduces mitochondria) biogenesis and ATP production. LETM1 acts as an anchor protein and associates with mitochondrial ribosome protein L36. Adenovirus-mediated overexpression of LETM1 reduced mitochondrial mass and expression of many mitochondrial proteins. LETM1-mediated inhibition of mitochondrial biogenesis enhanced glycolytic ATP supply and activated protein kinase B activity and cell survival signaling. The expression levels of LETM1 were significantly increased in multiple human cancer tissues compared with normals. These data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. The increased expression of LETM1 in human cancer suggests that deregulation of LETM1 is a key feature of tumorigenesis. [Cancer Res 2009;69(8):3397-404]

Out-of-field cell survival following exposure to intensity-modulated radiation fields

PURPOSE:
To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.
METHODS AND MATERIALS:
Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.
RESULTS:
Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the a-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.
CONCLUSIONS:
These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

Physicochemical characterisation and drug release properties of celecoxib hot melt extruded glass solutions

Formulation of Celecoxib into solid dosage forms is difficult due to the physical properties of the drug powder. However for the first time, this paper reports on the drug delivery characteristics glass solutions of celecoxib and polyvinylpyrrolidone prepared by hot melt extrusion, together with use of supercritical carbon dioxide to achieve a porous structure, in order to achieve a stable and enhanced drug release.

The schizophrenia phenotype in 22q11 deletion syndrome

Objective: This study investigated the schizophrenia phenotype in 24 subjects with 22q11 deletion syndrome (22qDS) and schizophrenia (22qDS-schizophrenia), a rare but relatively homogenous genetic subtype of schizophrenia associated with a microdeletion on chromosome 22. Individuals with 22qDS are at genetically high risk for schizophrenia.

The VLT-FLAMES Tarantula Survey I. Introduction and observational overview

The VLT-FLAMES Tarantula Survey (VFTS) is an ESO Large Programme that has obtained multi-epoch optical spectroscopy of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). Here we introduce our scientific motivations and give an overview of the survey targets, including optical and near-infrared photometry and comprehensive details of the data reduction. One of the principal objectives was to detect massive binary systems via variations in their radial velocities, thus shaping the multi-epoch observing strategy. Spectral classifications are given for the massive emission-line stars observed by the survey, including the discovery of a new Wolf-Rayet star (VFTS 682, classified as WN5h), 2' to the northeast of R136. To illustrate the diversity of objects encompassed by the survey, we investigate the spectral properties of sixteen targets identified by Gruendl & Chu from Spitzer photometry as candidate young stellar objects or stars with notable mid-infrared excesses. Detailed spectral classification and quantitative analysis of the O- and B-type stars in the VFTS sample, paying particular attention to the effects of rotational mixing and binarity, will be presented in a series of future articles to address fundamental questions in both stellar and cluster evolution.

Entangling two distant oscillators with a quantum reservoir

The generation of entanglement between two oscillators that interact via a common reservoir is theoretically studied. The reservoir is modeled by a one-dimensional harmonic crystal initially in thermal equilibrium. Starting from a separable state, the oscillators can become entangled after a transient time, that is of the order of the thermalization time scale. This behaviour is observed at finite temperature even when the oscillators are at a distance significantly larger than the crystal's interparticle spacing. The underlying physical mechanisms can be explained by the dynamical properties of the collective variables of the two oscillators which may decouple from or be squeezed by the reservoir. Our predictions can be tested with an ion chain in a linear Paul trap. Copyright (C) EPLA, 2011

Ceramium Roth (Ceramiales, Rhodophyta) from Venice lagoon (Adriatic Sea, Italy): Comparative studies of Mediterranean and Atlantic taxa

The cosmopolitan genus Ceramium (Ceramiaceae, Rhodophyta) is a large and systematically complex group. The taxonomy of this genus remains in a chaotic state due to the high degree of morphological variation. Culture studies, suggesting a strong influence of environment on phenotype, and the use of molecular tools have recently questioned the validity of morphological features used in species recognition. Here we compare three Ceramium taxa from Venice lagoon with samples from northwest Europe using the plastid ribulose-1,5-bisphosphate carboxylase/oxygenase gene (rbcL) and the rbcL-rbcS intergenic spacer combined with morphological observations. A strongly banded species, previously identified as member of a poorly understood and misnamed group, the Ceramium diaphanum complex sensu Feldmann-Mazoyer, is probably conspecific with British samples of Ceramium diaphanum sensu Harvey, for which no valid name has been identified up to now. We show that Ceramium polyceras (Kutzing) Zanardini is a valid name for this species. A fully corticated Ceramium species morphologically resembling C. secundatum differs at the species level from Atlantic C. secundatum; a valid name for this entity is Ceramium derbesii Solier ex Kutzing, described from Mediterranean France. A third species characterized by cortical spines, previously listed as Ceramium ciliation var. robustum (J. Agardh) Mazoyer, is shown to be Ceramium nudiusculum (Kutzing) Rabenhorst, originally described from Venice.

Pan-STARRS1 DISCOVERY OF TWO ULTRALUMINOUS SUPERNOVAE AT(z) approximate to 0.9

We present the discovery of two ultraluminous supernovae (SNe) at z approximate to 0.9 with the Pan-STARRS1 Medium Deep Survey. These SNe, PS1-10ky and PS1-10awh, are among the most luminous SNe ever discovered, comparable to the unusual transients SN 2005ap and SCP 06F6. Like SN 2005ap and SCP 06F6, they show characteristic high luminosities (M-bol approximate to -22.5 mag), blue spectra with a few broad absorption lines, and no evidence for H or He. We have constructed a full multi-color light curve sensitive to the peak of the spectral energy distribution in the rest-frame ultraviolet, and we have obtained time series spectroscopy for these SNe. Given the similarities between the SNe, we combine their light curves to estimate a total radiated energy over the course of explosion of (0.9-1.4) x 10(51) erg. We find photospheric velocities of 12,000-19,000 km s(-1) with no evidence for deceleration measured across similar to 3 rest-frame weeks around light curve peak, consistent with the expansion of an optically thick massive shell of material. We show that, consistent with findings for other ultraluminous SNe in this class, radioactive decay is not sufficient to power PS1-10ky, and we discuss two plausible origins for these events: the initial spin-down of a newborn magnetar in a core-collapse SN, or SN shock breakout from the dense circumstellar wind surrounding a Wolf-Rayet star.

Progenitors of Core-Collapse Supernovae

Knowledge of the progenitors of core-collapse supernovae is a fundamental component in understanding the explosions. The recent progress in finding such stars is reviewed. The minimum initial mass that can produce a supernova (SN) has converged to 8 +/- 1 M-circle dot from direct detections of red supergiant progenitors of II-P SNe and the most massive white dwarf progenitors, although this value is model dependent. It appears that most type Ibc SNe arise from moderate mass interacting binaries. The highly energetic, broad-lined Ic SNe are likely produced by massive, Wolf-Rayet progenitors. There is some evidence to suggest that the majority of massive stars above similar to 20 M-circle dot may collapse quietly to black holes and that the explosions remain undetected. The recent discovery of a class of ultrabright type H SNe and the direct detection of some progenitor stars bearing luminous blue variable characteristics suggest some very massive stars do produce highly energetic explosions. The physical mechanism is under debate, and these SNe pose a challenge to stellar evolutionary theory.

Massive stars exploding in a He-rich circumstellar medium - I. Type Ibn (SN 2006jc-like) events

We present new spectroscopic and photometric data of the Type Ibn supernovae 2006jc, 2000er and 2002ao. We discuss the general properties of this recently proposed supernova family, which also includes SN 1999cq. The early-time monitoring of SN 2000er traces the evolution of this class of objects during the first few days after the shock breakout. An overall similarity in the photometric and spectroscopic evolution is found among the members of this group, which would be unexpected if the energy in these core-collapse events was dominated by the interaction between supernova ejecta and circumstellar medium. Type Ibn supernovae appear to be rather normal Type Ib/c supernova explosions which occur within a He-rich circumstellar environment. SNe Ibn are therefore likely produced by the explosion of Wolf-Rayet progenitors still embedded in the He-rich material lost by the star in recent mass-loss episodes, which resemble known luminous blue variable eruptions. The evolved Wolf-Rayet star could either result from the evolution of a very massive star or be the more evolved member of a massive binary system. We also suggest that there are a number of arguments in favour of a Type Ibn classification for the historical SN 1885A (S-Andromedae), previously considered as an anomalous Type la event with some resemblance to SN 1991bg.

Massive stars exploding in a He-rich circumstellar medium - II. The transitional case of SN 2005la

We present photometric and spectroscopic data of the peculiar SN 2005la, an object which shows an optical light curve with some luminosity fluctuations and spectra with comparably strong narrow hydrogen and helium lines, probably of circumstellar nature. The increasing full width at half-maximum velocity of these lines is indicative of an acceleration of the circumstellar material. SN 2005la exhibits hybrid properties, sharing some similarities with both Type IIn supernovae and 2006jc-like (Type Ibn) events. We propose that the progenitor of SN 2005la was a very young Wolf-Rayet (WN-type) star which experienced mass ejection episodes shortly before core collapse.

The type IIb SN 2008ax: the nature of the progenitor

A source coincident with the position of the type IIb supernova (SN) 2008ax is identified in pre-explosion Hubble Space Telescope (HST) Wide Field Planetary Camera 2 observations in three optical filters. We identify and constrain two possible progenitor systems: (i) a single massive star that lost most of its hydrogen envelope through radiatively driven mass-loss processes, prior to exploding as a helium-rich Wolf-Rayet star with a residual hydrogen envelope, and (ii) an interacting binary in a low-mass cluster producing a stripped progenitor. Late time, high-resolution observations along with detailed modelling of the SN will be required to reveal the true nature of this progenitor star.

The Type IIb SN 2008ax: spectral and light curve evolution

We present spectroscopy and photometry of the He-rich supernova (SN) 2008ax. The early-time spectra show prominent P-Cygni H lines, which decrease with time and disappear completely about 2 months after the explosion. In the same period He I lines become the most prominent spectral features. SN 2008ax displays the ordinary spectral evolution of a Type IIb supernova. A stringent pre-discovery limit constrains the time of the shock breakout of SN 2008ax to within only a few hours. Its light curve, which peaks in the B band about 20 d after the explosion, strongly resembles that of other He-rich core-collapse supernovae. The observed evolution of SN 2008ax is consistent with the explosion of a young Wolf-Rayet (of WNL type) star, which had retained a thin, low-mass shell of its original H envelope. The overall characteristics of SN 2008ax are reminiscent of those of SN 1993J, except for a likely smaller H mass. This may account for the findings that the progenitor of SN 2008ax was a WNL star and not a K supergiant as in the case of SN 1993J, that a prominent early-time peak is missing in the light curve of SN 2008ax, and that H alpha is observed at higher velocities in SN 2008ax than in SN 1993J.

A deeper search for the progenitor of the Type Ic supernova 2002ap

Images of the site of the Type Ic supernova (SN) 2002ap taken before explosion were analysed previously by Smartt et al. We have uncovered new unpublished, archival pre-explosion images from the Canada-France-Hawaii Telescope (CFHT) that are vastly superior in depth and image quality. In this paper we present a further search for the progenitor star of this unusual Type Ic SN. Aligning high-resolution Hubble Space Telescope observations of the SN itself with the archival CFHT images allowed us to pinpoint the location of the progenitor site on the groundbased observations. We find that a source visible in the B- and R-band pre-explosion images close to the position of the SN is (1) not coincident with the SN position within the uncertainties of our relative astrometry and (2) is still visible similar to 4.7-yr post-explosion in late-time observations taken with the William Herschel Telescope. We therefore conclude that it is not the progenitor of SN 2002ap. We derived absolute limiting magnitudes for the progenitor of M-B >= -4.2 +/- 0.5 and M-R >= -5.1 +/- 0.5. These are the deepest limits yet placed on a Type Ic SN progenitor. We rule out all massive stars with initial masses greater than 7-8 M-circle dot (the lower mass limit for stars to undergo core collapse) that have not evolved to become Wolf-Rayet stars. This is consistent with the prediction that Type Ic SNe should result from the explosions of Wolf-Rayet stars. Comparing our luminosity limits with stellar models of single stars at appropriate metallicity (Z = 0.008) and with standard mass-loss rates, we find no model that produces a Wolf-Rayet star of low enough mass and luminosity to be classed as a viable progenitor. Models with twice the standard mass-loss rates provide possible single star progenitors but all are initially more massive than 30-40 M-circle dot. We conclude that any single star progenitor must have experienced at least twice the standard mass-loss rates, been initially more massive than 30-40 M-circle dot and exploded as a Wolf-Rayet star of final mass 10-12 M-circle dot. Alternatively a progenitor star of lower initial mass may have evolved in an interacting binary system. Mazzali et al. propose such a binary scenario for the progenitor of SN 2002ap in which a star of initial mass 15-20 M-circle dot is stripped by its binary companion, becoming a 5 M-circle dot Wolf-Rayet star prior to explosion. We constrain any possible binary companion to a main-sequence star of

The WR content of IC10 - first detection of WC9 stars in a low metallicity environment?

We present deep, narrow-hand photometry of the Local Group starburst galaxy IC10. Our dedicated photometric system provides detection of 13 new Wolf-Rayet (WR) stars and allows spectral subtypes to be assigned. Three of these new stars appear to be WC9 subtypes. If confirmed, these would be the very first WC9 stars ever detected in a low metallicity environment, hence putting strong new constraints on the formation and evolution models of massive stars. Eight of the new WR stars are of the WC subtype, which does not significantly modify the anomalously high WC/WN ratio in IC10. However it is likely that a number of Wolf-Rayet stars of the WNE and WC spectral subtypes are still to be discovered in the heart of the galaxy.