ALBERT

Description: We present CO observations towards a sample of six H i-rich Ultradiffuse galaxies (UDGs) as well as one UDG (VLSB-A) in the Virgo Cluster with the Institut de RadioAstronomie Millimétrique (IRAM) 30-m telescope. CO J = 1–0 is marginally detected at 4σ level in AGC 122966, as the first detection of CO emission in UDGs. We estimate upper limits of molecular mass in other galaxies from the non-detection of CO lines. These upper limits and the marginal CO detection in AGC 122966 indicate low mass ratios between molecular and atomic gas masses. With the star formation efficiency derived from the molecular gas, we suggest that the inefficiency of star formation in such H i-rich UDGs is likely caused by the low efficiency in converting molecules from atomic gas, instead of low efficiency in forming stars from molecular gas.

Description: We find that the minor axes of the ultra-diffuse galaxies (UDGs) in Abell 2634 tend to be aligned with the major axis of the central dominant galaxy, at a $gtrsim 95{{ m per cent}}$ confidence level. This alignment is produced by the bright UDGs with the absolute magnitudes Mr 〈 −15.3 mag, and outer-region UDGs with R 〉 0.5R200. The alignment signal implies that these bright, outer-region UDGs are very likely to acquire their angular momenta from the vortices around the large-scale filament before they were accreted into A2634, and form their extended stellar bodies outside of the cluster; in this scenario, the orientations of their primordial angular momenta, which are roughly shown by their minor axes on the images, should tend to be parallel to the elongation of the large-scale filament. When these UDGs fell into the unrelaxed cluster A2634 along the filament, they could still preserve their primordial alignment signal before violent relaxation and encounters. These bright, outer-region UDGs in A2634 are very unlikely to be the descendants of the high-surface-brightness dwarf progenitors under tidal interactions with the central dominant galaxy in the cluster environment. Our results indicate that the primordial alignment could be a useful probe of the origin of UDGs in large-scale structures.

Description: We present a detailed analysis of the gaseous component of the Si K edge using high-resolution Chandra spectra of low-mass X-ray binaries. We fit the spectra with a modified version of the ISMabs model, including new photoabsorption cross-sections computed for all Si ionic species. We estimate column densities for Si i, Si ii, Si iii, Si xii, and Si xiii, which trace the warm, intermediate temperature, and hot phases of the Galactic interstellar medium. We find that the ionic fractions of the first two phases are similar. This may be due to the physical state of the plasma determined by the temperature or due to the presence of absorber material in the close vicinity of the sources. Our findings highlight the need for accurate modelling of the gaseous component before attempting to address the solid component.

Description: Using state-of-the-art high-resolution fully GPU N-body simulations, we demonstrate for the first time that the infall of a dark matter-rich satellite naturally explains a present black hole offset by subparsecs in M31. Observational data of the tidal features provide stringent constraints on the initial conditions of our simulations. The heating of the central region of M31 by the satellite via dynamical friction entails a significant black hole offset after the first pericentric passage. After having reached its maximum offset, the massive black hole sinks towards the M31 centre due to dynamical friction and it is determined to be offset by subparsecs as derived by observations.

Description: In two recent papers published in MNRAS, Namouni and Morais claimed evidence for the interstellar origin of some small Solar system bodies, including: (i) objects in retrograde co-orbital motion with the giant planets and (ii) the highly inclined Centaurs. Here, we discuss the flaws of those papers that invalidate the authors’ conclusions. Numerical simulations backwards in time are not representative of the past evolution of real bodies. Instead, these simulations are only useful as a means to quantify the short dynamical lifetime of the considered bodies and the fast decay of their population. In light of this fast decay, if the observed bodies were the survivors of populations of objects captured from interstellar space in the early Solar system, these populations should have been implausibly large (e.g. about 10 times the current main asteroid belt population for the retrograde co-orbital of Jupiter). More likely, the observed objects are just transient members of a population that is maintained in quasi-steady state by a continuous flux of objects from some parent reservoir in the distant Solar system. We identify in the Halley-type comets and the Oort cloud the most likely sources of retrograde co-orbitals and highly inclined Centaurs.

Description: Strong gravitational lensing has been a powerful probe of cosmological models and gravity. To date, constraints in either domain have been obtained separately. We propose a new methodology through which the cosmological model, specifically the Hubble constant, and post-Newtonian parameter can be simultaneously constrained. Using the time-delay cosmography from strong lensing combined with the stellar kinematics of the deflector lens, we demonstrate that the Hubble constant and post-Newtonian parameter are incorporated in two distance ratios that reflect the lensing mass and dynamical mass, respectively. Through the re-analysis of the four publicly released lenses distance posteriors from the H0LiCOW (H0 Lenses in COSMOGRAIL’s Wellspring) collaboration, the simultaneous constraints of Hubble constant and post-Newtonian parameter are obtained. Our results suggest no deviation from the general relativity; $gamma _{t {PPN}}=0.87^{+0.19}_{-0.17}$ with a Hubble constant that favours the local Universe value, $H_0=73.65^{+1.95}_{-2.26}$ km s−1 Mpc−1. Finally, we forecast the robustness of gravity tests by using the time-delay strong lensing for constraints we expect in the next few years. We find that the joint constraint from 40 lenses is able to reach the order of $7.7{{ m per cent}}$ for the post-Newtonian parameter and $1.4{{ m per cent}}$ for the Hubble constant.

Description: One of the proposed channels of binary black hole mergers involves dynamical interactions of three black holes. In such scenarios, it is possible that all three black holes merge in a so-called hierarchical merger chain, where two of the black holes merge first and then their remnant subsequently merges with the remaining single black hole. Depending on the dynamical environment, it is possible that both mergers will appear within the observable time window. Here, we perform a search for such merger pairs in the public available LIGO and Virgo data from the O1/O2 runs. Using a frequentist p-value assignment statistics, we do not find any significant merger pair candidates, the most significant being GW170809-GW151012 pair. Assuming no observed candidates in O3/O4, we derive upper limits on merger pairs to be ∼11–110 yr−1 Gpc−3, corresponding to a rate that relative to the total merger rate is ∼0.1−1.0. From this, we argue that both a detection and a non-detection within the next few years can be used to put useful constraints on some dynamical progenitor models.

Description: We present extremely deep upper limits on the radio emission from 4U 1957+11, an X-ray binary that is generally believed to be a persistently accreting black hole that is almost always in the soft state. We discuss a more comprehensive search for Type I bursts than in past work, revealing a stringent upper limit on the burst rate, bolstering the case for a black hole accretor. The lack of detection of this source at the 1.07 μJy/beam noise level indicates jet suppression that is stronger than expected even in the most extreme thin disc models for radio jet production – the radio power here is 1500–3700 times lower than the extrapolation of the hard state radio/X-ray correlation, with the uncertainties depending primarily on the poorly constrained source distance. We also discuss the location and velocity of the source and show that it must have either formed in the halo or with a strong asymmetric natal kick.

Description: Swift J004427.3−734801 is an X-ray source in the Small Magellanic Cloud (SMC) that was first discovered as part of the Swift S-CUBED programme in 2020 January. It was not detected in any of the previous 3 yr worth of observations. The accurate positional determination from the X-ray data has permitted an optical counterpart to be identified that has the characteristics of an O9V−B2III star. Evidence for the presence of an infrared excess and significant I-band variability strongly suggests that this is an OBe-type star. Over 17 yr worth of optical monitoring by the OGLE (Optical Gravitational Lensing Experiment) project reveals periods of time in which quasi-periodic optical flares occur at intervals of ∼21.5 d. The X-ray data obtained from the S-CUBED project reveal a very soft spectrum, too soft to be that from accretion on to a neutron star or black hole. It is suggested here that this is a rarely identified Be star–white dwarf binary in the SMC.

Description: Gravitational microlensing can detect isolated stellar-mass black holes (BHs), which are believed to be the dominant form of Galactic BHs according to population synthesis models. Previous searches for BH events in microlensing data focused on long time-scale events with significant microlensing parallax detections. Here we show that, although BH events preferentially have long time-scales, the microlensing parallax amplitudes are so small that in most cases the parallax signals cannot be detected statistically significantly. We then identify OGLE-2006-BLG-044 to be a candidate BH event because of its long time-scale and small microlensing parallax. Our findings have implications to future BH searches in microlensing data.

Description: We present a sub-100 pc-scale analysis of the CO molecular gas emission and kinematics of the gravitational lens system SDP.81 at redshift 3.042 using Atacama Large Millimetre/submillimetre Array (ALMA) science verification data and a visibility-plane lens reconstruction technique. We find clear evidence for an excitation-dependent structure in the unlensed molecular gas distribution, with emission in CO (5–4) being significantly more diffuse and structured than in CO (8–7). The intrinsic line luminosity ratio is r 8–7/5–4  = 0.30 ± 0.04, which is consistent with other low-excitation starbursts at z  ~ 3. An analysis of the velocity fields shows evidence for a star-forming disc with multiple velocity components that is consistent with a merger/post-coalescence merger scenario, and a dynamical mass of M (〈1.56 kpc) = 1.6 ± 0.6  x  10 10 M . Source reconstructions from ALMA and the Hubble Space Telescope show that the stellar component is offset from the molecular gas and dust components. Together with Karl G. Jansky Very Large Array CO (1–0) data, they provide corroborative evidence for a complex ~2 kpc-scale starburst that is embedded within a larger ~15 kpc structure.

Description: It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18–83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16–1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio ( P 〈 0.05) and plasma concentrations of glycosylated hemoglobin ( P = 0.07). However, multivariate regression analysis only showed an inverse association between age and DNA repair activity ( P 〈 0.05), indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary, the results show an inverse association between age and DNA repair activity of oxidatively damaged DNA.

Description: Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55–83 years and body mass index above 25kg/m 2 were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM 2.5 levels of 1800/cm 3 versus 23 000/cm 3 and 3 µg/m 3 versus 24 µg/m 3 , respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation ( chemokine (C-C motif) ligand 2 , interleukin-8 and tumour necrosis factor ), oxidative stress response ( heme oxygenase (decycling)-1 ) and DNA repair ( oxoguanine DNA glycosylase ). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.

Description: Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only ( P 〈 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.

Description: Regardless of the physical origin of stellar magnetic fields – fossil or dynamo induced - an inclination angle between the magnetic and rotation axes is very often observed. Absence of observational evidence in this direction in the solar case has led to generally assume that its global magnetic field and rotation axes are well aligned. We present the detection of a monthly periodic signal of the photospheric solar magnetic field at all latitudes, and especially near the poles, revealing that the main axis of the Sun's magnetic field is not aligned with the surface rotation axis. This result reinforces the view of our Sun as a common intermediate-mass star. Furthermore, this detection challenges and imposes a strong observational constraint to modern solar dynamo theories.

Description: We use the ‘Evolution and Assembly of GaLaxies and their Environments’ ( eagle ) suite of hydrodynamical cosmological simulations to measure offsets between the centres of stellar and dark matter components of galaxies. We find that the vast majority (〉95 per cent) of the simulated galaxies display an offset smaller than the gravitational softening length of the simulations (Plummer-equivalent  = 700 pc), both for field galaxies and satellites in clusters and groups. We also find no systematic trailing or leading of the dark matter along a galaxy's direction of motion. The offsets are consistent with being randomly drawn from a Maxwellian distribution with  ≤ 196 pc. Since astrophysical effects produce no feasible analogues for the $1.62^{+0.47}_{-0.49}$  kpc offset recently observed in Abell 3827, the observational result is in tension with the collisionless cold dark matter model assumed in our simulations.

Description: The solar wind magnetic field contains rotations at a broad range of scales, which have been extensively studied in the magnetohydrodynamics range. Here, we present an extension of this analysis to the range between ion and electron kinetic scales. The distribution of rotation angles was found to be approximately lognormal, shifting to smaller angles at smaller scales almost self-similarly, but with small, statistically significant changes of shape. The fraction of energy in fluctuations with angles larger than α was found to drop approximately exponentially with α, with e-folding angle 9.8° at ion scales and 0 $_{.}^{\circ}$ 66 at electron scales, showing that large angles (α 〉 30°) do not contain a significant amount of energy at kinetic scales. Implications for kinetic turbulence theory and the dissipation of solar wind turbulence are discussed.

Description: We report the broad-band spectral properties of the X-ray pulsar Cep X-4 by using a Suzaku observation in 2014 July. The 0.8–70 keV spectrum was found to be well described by three continuum models – Negative and Positive power-law with Exponential cut-off (NPEX), high-energy cut-off power-law and CompTT models. Additional components such as a cyclotron line at ~28 keV and two Gaussian components for iron lines at 6.4 and 6.9 keV were required in the spectral fitting. Apart from these, an additional absorption feature at ~45 keV was clearly detected in residuals obtained from the spectral fitting. This additional feature at ~45 keV was clearly seen in phase-resolved spectra of the pulsar. We identified this feature as the first harmonic of the fundamental cyclotron line at ~28 keV. The ratio between the first harmonic and fundamental line energies (1.7) was found to be in disagreement with the conventional factor of 2, indicating that the heights of line-forming regions are different or viewed at larger angles. The phase-resolved spectroscopy of the fundamental and first harmonic cyclotron lines shows significant pulse-phase variation of the line parameters. This can be interpreted as the effect of viewing angle or the role of complicated magnetic field of the pulsar.

Description: The spin-down of a neutron star, e.g. due to magneto-dipole losses, results in compression of the stellar matter and induces nuclear reactions at phase transitions between different nuclear species in the crust. We show that this mechanism is effective in heating recycled pulsars, in which the previous accretion process has already been compressing the crust, so it is not in nuclear equilibrium. We calculate the corresponding emissivity and confront it with available observations, showing that it might account for the likely thermal ultraviolet emission of PSR J0437–4715.

Description: New insights into the formation of interstellar formamide, a species of great relevance in prebiotic chemistry, are provided by electronic structure and kinetic calculations for the reaction NH 2 + H 2 CO -〉 NH 2 CHO + H. Contrarily to what previously suggested, this reaction is essentially barrierless and can, therefore, occur under the low temperature conditions of intestellar objects thus providing a facile formation route of formamide. The rate coefficient parameters for the reaction channel leading to NH 2 CHO + H have been calculated to be A = 2.6 x 10 –12  cm 3  s –1 , β = –2.1 and = 26.9 K in the range of temperatures 10–300 K. Including these new kinetic data in a refined astrochemical model, we show that the proposed mechanism can well reproduce the abundances of formamide observed in two very different interstellar objects: the cold envelope of the Sun-like protostar IRAS16293–2422 and the molecular shock L1157-B2. Therefore, the major conclusion of this Letter is that there is no need to invoke grain-surface chemistry to explain the presence of formamide provided that its precursors, NH 2 and H 2 CO, are available in the gas phase.

Description: Recent Low-Frequency Array (LOFAR) observations at 115–175 MHz of a field at medium Galactic latitudes (centred at the bright quasar 3C196) have shown striking filamentary structures in polarization that extend over more than 4° across the sky. In addition, the Planck satellite has released full sky maps of the dust emission in polarization at 353 GHz. The LOFAR data resolve Faraday structures along the line of sight, whereas the Planck dust polarization maps probe the orientation of the sky projected magnetic field component. Hence, no apparent correlation between the two is expected. Here we report a surprising, yet clear, correlation between the filamentary structures, detected with LOFAR, and the magnetic field orientation, probed by the Planck satellite. This finding points to a common, yet unclear, physical origin of the two measurements in this specific area in the sky. A number of follow-up multifrequency studies are proposed to shed light on this unexpected finding.

Description: Protoplanetary discs are now routinely observed and exoplanets, after the numerous indirect discoveries, are starting to be directly imaged. To better understand the planet formation process, the next step is the detection of forming planets or of signposts of young planets still in their disc, such as gaps. A spectacular example is the Atacama Large Millimeter/submillimeter Array (ALMA) science verification image of HL Tau showing numerous gaps and rings in its disc. To study the observability of planet gaps, we ran 3D hydrodynamical simulations of a gas and dust disc containing a 5 M J gap-opening planet and characterized the spatial distribution of migrating, growing and fragmenting dust grains. We then computed the corresponding synthetic images for ALMA. For a value of the dust fragmentation threshold of 15 m s –1 for the collisional velocity, we identify for the first time a self-induced dust pile-up in simulations taking fragmentation into account. This feature, in addition to the easily detected planet gap, causes a second apparent gap that could be mistaken for the signature of a second planet. It is therefore essential to be cautious in the interpretation of gap detections.

Description: Recent observations have discovered a number of extremely gas-rich very faint dwarf galaxies possibly embedded in low-mass dark matter haloes. We investigate star formation histories of these gas-rich dwarf (‘almost dark’) galaxies both for isolated and interacting/merging cases. We find that although star formation rates (SFRs) are very low (〈10 –5 M  yr –1 ) in the simulated dwarfs in isolation for the total halo masses ( M h ) of 10 8 -10 9 M , they can be dramatically increased to be ~10 –4 M  yr –1 when they interact or merge with other dwarfs. These interacting faint dwarfs with central compact H ii regions can be identified as isolated emission line dots (‘ELdots’) owing to their very low surface brightness envelopes of old stars. The remnant of these interacting and merging dwarfs can finally develop central compact stellar systems with very low metallicities ( Z /Z  〈 0.1), which can be identified as extremely metal-deficient (‘XMD’) dwarfs. These results imply that although there would exist many faint dwarfs that can be hardly detected in the current optical observations, they can be detected as isolated ELdots or XMD dwarfs, when they interact with other galaxies and their host environments. We predict that nucleated ultrafaint dwarfs formed from the darkest dwarf merging can be identified as low-mass globular clusters owing to the very low surface brightness stellar envelopes.

Description: The BRITE ( BRIght Target Explorer ) constellation of nanosatellites performs seismology of bright stars via high-precision photometry. In this context, we initiated a high-resolution, high signal-to-noise, high-sensitivity, spectropolarimetric survey of all stars brighter than V = 4. The goal of this survey is to detect new bright magnetic stars and provide prime targets for both detailed magnetic studies and asteroseismology with BRITE . Circularly polarized spectra were acquired with Narval at TBL (Bernard Lyot Telescope, France) and HARPSpol at ESO (European Southern Observatory) in La Silla (Chile). We discovered two new magnetic B stars: the B3V star i Car and the B8V component of the binary star Atlas. Each star was observed twice to confirm the magnetic detections and check for variability. These bright magnetic B stars are prime targets for asteroseismology and for flux-demanding techniques, such as interferometry.

Description: Accreting neutron stars exhibit Type I X-ray bursts from both frequent hydrogen/helium flashes as well as rare carbon flashes. The latter (superbursts) ignite in the ashes of the former. Hydrogen/helium bursts, however, are thought to produce insufficient carbon to power superbursts. Stable burning could create the required carbon, but this was predicted to only occur at much larger accretion rates than where superbursts are observed. We present models of a new steady-state regime of stable hydrogen and helium burning that produces pure carbon ashes. Hot CNO burning of hydrogen heats the neutron star envelope and causes helium to burn before the conditions of a helium flash are reached. This takes place when the mass accretion rate is around 10 per cent of the Eddington limit: close to the rate where most superbursts occur. We find that increased heating at the base of the envelope sustains steady-state burning by steepening the temperature profile, which increases the amount of helium that burns before a runaway can ensue.

Description: We present new late-time near-infrared imaging of the site of the nearby core-collapse supernova SN 2012aw, confirming the disappearance of the point source identified by Fraser et al. and Van Dyk et al. as a candidate progenitor in both J and Ks filters. We remeasure the progenitor photometry, and find that both the J and Ks magnitudes of the source are consistent with those quoted in the literature. We also recover a marginal detection of the progenitor in H -band, for which we measure H = 19.67 ± 0.40 mag. Comparing the luminosity of the progenitor to stellar evolutionary models, SN 2012aw appears to have resulted from the explosion of a 12.5 ± 1.5 M red supergiant.

Description: We derive the carbon monoxide (CO) luminosity function (LF) for different rotational transitions [i.e. (1–0), (3–2), (5–4)] starting from the Herschel LF by Gruppioni et al. and using appropriate L CO – L IR conversions for different galaxy classes. Our predicted LFs fit the data so far available at z 0 and 2. We compare our results with those obtained by semi-analytical models (SAMs): while we find a good agreement over the whole range of luminosities at z 0, at z 1 and z 2, the tension between our LFs and SAMs in the faint and bright ends increases. We finally discuss the contribution of luminous active galactic nucleus ( L X 〉 10 44 erg s – 1 ) to the bright end of the CO LF concluding that they are too rare to reproduce the actual CO LF at z 2.

Description: The formation of the Milky Way stellar halo is thought to be the result of merging and accretion of building blocks such as dwarf galaxies and massive globular clusters. Recently, Deason et al. suggested that the Milky Way outer halo formed mostly from big building blocks, such as dwarf spheroidal galaxies, based on the similar number ratio of blue straggler (BS) stars to blue horizontal branch (BHB) stars. Here we demonstrate, however, that this result is seriously biased by not taking into detailed consideration on the formation mechanism of BHB stars from helium-enhanced second-generation population. In particular, the high BS-to-BHB ratio observed in the outer halo fields is most likely due to a small number of BHB stars provided by globular clusters (GCs) rather than to a large number of BS stars. This is supported by our dynamical evolution model of GCs which shows preferential removal of first-generation stars in GCs. Moreover, there are a sufficient number of outer halo GCs which show very high BS-to-BHB ratio. Therefore, the BS-to-BHB number ratio is not a good indicator to use in arguing that more massive dwarf galaxies are the main building blocks of the Milky Way outer halo. Several lines of evidence still suggest that GCs can contribute a significant fraction of the outer halo stars.

Description: Nuclear star clusters (NCs) are found to exist in the centres of many galaxies and appear to follow scaling relations similar to those of supermassive black holes. Previous analytical work has suggested that such relations are a consequence of feedback-regulated growth. We explore this idea using high-resolution hydrodynamical simulations, focusing on the validity of the simplifying assumptions made in analytical models. In particular, we investigate feedback emanating from multiple stellar sources rather than from a single source, as is usually assumed, and show that collisions between shells of gas swept up by feedback leads to momentum cancellation and the formation of high-density clumps and filaments. This high-density material is resistant both to expulsion from the galaxy potential and to disruption by feedback; if it falls back on to the NC, we expect the gas to be available for further star formation or for feeding a central black hole. We also note that our results may have implications for the evolution of globular clusters and stellar clusters in high-redshift dark matter haloes.

Description: We explain the axisymmetric gaps seen in recent long-baseline observations of the HL Tau protoplanetary disc with the Atacama Large Millimetre/Submillimetre Array (ALMA) as being due to the different response of gas and dust to embedded planets in protoplanetary discs. We perform global, three-dimensional dusty smoothed particle hydrodynamics calculations of multiple planets embedded in dust/gas discs which successfully reproduce most of the structures seen in the ALMA image. We find a best match to the observations using three embedded planets with masses of 0.2, 0.27 and 0.55 M J in the three main gaps observed by ALMA, though there remain uncertainties in the exact planet masses from the disc model.

Description: Using deep Herschel and ALMA observations, we investigate the star formation rate (SFR) distributions of X-ray-selected active galactic nucleus (AGN) host galaxies at 0.5 〈  z  〈 1.5 and 1.5 〈  z  〈 4, comparing them to that of normal, star-forming (i.e. ‘main-sequence’, or MS) galaxies. We find that 34–55 per cent of AGNs in our sample have SFRs at least a factor of 2 below that of the average MS galaxy, compared to 15 per cent of all MS galaxies, suggesting significantly different SFR distributions. Indeed, when both are modelled as lognormal distributions, the mass and redshift-normalized SFR distributions of X-ray AGNs are roughly twice as broad, and peak 0.4 dex lower, than that of MS galaxies. However, like MS galaxies, the normalized SFR distribution of AGNs in our sample appears not to evolve with redshift. Despite X-ray AGNs and MS galaxies having different SFR distributions, the linear-mean SFR of AGNs derived from our distributions is remarkably consistent with that of MS galaxies, and thus with previous results derived from stacked Herschel data. This apparent contradiction is due to the linear-mean SFR being biased by bright outliers, and thus does not necessarily represent a true characterization of the typical SFR of X-ray AGNs.

Description: We investigate the density–shear instability in Hall-magnetohydrodynamics (Hall-MHD) via numerical simulation of the full non-linear problem in the context of magnetar activity. We confirm the development of the instability of a plane-parallel magnetic field with an appropriate intensity and electron density profile, in accordance with analytic theory. We find that the instability also appears for a monotonically decreasing electron number density and magnetic field, a plane-parallel analogue of an azimuthal or meridional magnetic field in the crust of a magnetar. The growth rate of the instability depends on the Hall properties of the field (magnetic field intensity, electron number density and the corresponding scaleheights), while being insensitive to weak resistivity. Since the Hall effect is the driving process for the evolution of the crustal magnetic field of magnetars, we argue that this instability is critical for systems containing strong meridional or azimuthal fields. We find that this process mediates the formation of localized structures with much stronger magnetic field than the average, which can lead to magnetar activity and accelerate the dissipation of the field and consequently the production of Ohmic heating. Assuming a 5  x  10 14  G magnetic field at the base of crust, we anticipate that magnetic field as strong as 10 15  G will easily develop in regions of typical size of a few hundred metres, containing magnetic energy of 10 43  erg, sufficient to power magnetar bursts. These active regions are more likely to appear in the magnetic equator where the tangential magnetic field is stronger.

Description: Long expected transition states between the rotation powered and accretion powered non-thermal emission in the millisecond pulsar binary systems have been recently observed in the case of three objects PSR J1023+0038, PSR J1824–2452, and PSR J1227–4859. Surprisingly, the transition is related to the significant change in the -ray flux being a factor of a few higher with the presence of an accretion disc. The origin of this enhanced emission seems to be related to the penetration of the inner pulsar magnetosphere by the accretion disc. We propose that the radiation processes, characteristic for the rotation powered pulsar, can co-exist with the presence of an accretion disc in the inner pulsar magnetosphere. In our scenario additional -ray emission is produced by secondary leptons, originated close to the acceleration gap, which Compton up-scatter thermal radiation from the accretion disc to GeV energies. The accretion disc penetrates deep into the pulsar magnetosphere allowing the matter to fall on to the neutron star surface producing pulsed X-ray emission. We show that the sum of the rotation powered pulsar -ray emission, produced by the primary electrons in the curvature process, and the -ray emission, produced by secondary leptons, can explain the observed high-energy radiation from the redback binary pulsar PSR J1227–4853 in the state with evidences of the accretion disc.

Description: In the context of the ASAI (Astrochemical Surveys At IRAM) project, we carried out an unbiased spectral survey in the millimetre window towards the well known low-mass Class I source SVS13-A. The high sensitivity reached (3–12 mK) allowed us to detect at least six HDO broad (full width at half-maximum ~4–5 km s –1 ) emission lines with upper level energies up to E u = 837 K. A non-local thermodynamic equilibrium Large Velocity Gradient (LVG) analysis implies the presence of very hot (150–260 K) and dense (≥3  x  10 7  cm –3 ) gas inside a small radius (~25 au) around the star, supporting, for the first time, the occurrence of a hot corino around a Class I protostar. The temperature is higher than expected for water molecules are sublimated from the icy dust mantles (~100 K). Although we cannot exclude we are observing the effects of shocks and/or winds at such small scales, this could imply that the observed HDO emission is tracing the water abundance jump expected at temperatures ~220–250 K, when the activation barrier of the gas phase reactions leading to the formation of water can be overcome. We derive X ( HDO ) ~ 3  x  10 –6 , and a H 2 O deuteration ≥1.5  x  10 –2 , suggesting that water deuteration does not decrease as the protostar evolves from the Class 0 to the Class I stage.

Description: Evidence for the presence of quasi-periodic oscillations (QPOs) in the optical polarization of the blazar PKS 2155–304, during a period of enhanced gamma-ray brightness, is presented. The periodogram of the polarized flux revealed the existence of a prominent peak at T ~ 13 min, detected at 〉99.7 per cent significance, and T ~ 30 min, which was nominally significant at 〉99 per cent. This is the first evidence of QPOs in the polarization of an active galactic nucleus, potentially opening up a new avenue of studying this phenomenon.

Description: The spectrum and morphology of the diffuse Galactic -ray emission carries valuable information on cosmic ray (CR) propagation. Recent results obtained by analyzing Fermi -LAT data accumulated over 7 yr of observation show a substantial variation of the CR spectrum as a function of the distance from the Galactic Centre. The spatial distribution of the CR density in the outer Galaxy appears to be weakly dependent upon the galactocentric distance, as found in previous studies as well, while the density in the central region of the Galaxy was found to exceed the value measured in the outer Galaxy. At the same time, Fermi -LAT data suggest a gradual spectral softening while moving outwards from the centre of the Galaxy to its outskirts. These findings represent a challenge for standard calculations of CR propagation based on assuming a uniform diffusion coefficient within the Galactic volume. Here, we present a model of non-linear CR propagation in which transport is due to particle scattering and advection off self-generated turbulence. We find that for a realistic distribution of CR sources following the spatial distribution of supernova remnants and the space dependence of the magnetic field on galactocentric distance, both the spatial profile of CR density and the spectral softening can easily be accounted for.

Description: The correlation between the frequency and the absolute value of the frequency derivative of the kilohertz quasi-periodic oscillations (QPOs) observed for the first time from 4U 1636-53 is a simple consequence and indicator of the existence of a non-Keplerian rotation rate in the accretion disc boundary layer. This Letter interprets the observed correlation, showing that the observations provide strong evidence in support of the fundamental assumption of disc accretion models around slow rotators, that the boundary layer matches the Keplerian disc to the neutron star magnetosphere.

Description: During their formation phase, stars gain most of their mass in violent episodic accretion events, such as observed in FU Orionis (FUor) and EXor stars. V346 Normae is a well-studied FUor that underwent a strong outburst beginning around 1980. Here, we report on photometric and spectroscopic observations, which show that the visual/near-infrared brightness has decreased dramatically between the 1990s and 2010 ( R 10.9 mag, J 7.8 mag and K 5.8 mag). The spectral properties of this fading event cannot be explained by variable extinction alone, but indicate a drop in accretion rate by two to three orders of magnitude. This is the first time that a member of the FUor class has been observed to switch to a very low accretion phase. Remarkably, in the last few years (2011–2015) V346 Nor has brightened again at all near-infrared wavelengths, indicating the onset of a new outburst event. The observed behaviour might be consistent with the clustered luminosity bursts that have been predicted by recent gravitational instability and fragmentation models for the early stages of protostellar evolution. Given V346 Nor's unique characteristics (concerning outburst duration, repetition frequency and spectroscopic diagnostics), our results also highlight the need to revisit the FUor/EXor classification scheme.

Description: Approximately 0.2 ± 0.2 of white dwarfs (WDs) show signs of pollution by metals, which is likely due to the accretion of tidally disrupted planetary material. Models invoking planet–planet interactions after WD formation generally cannot explain pollution at cooling times of several Gyr. We consider a scenario in which a planet is perturbed by Lidov–Kozai oscillations induced by a binary companion and exacerbated by stellar mass-loss, explaining pollution at long cooling times. Our computed accretion rates are consistent with observations assuming planetary masses between ~0.01 and 1 M Mars , although non-gravitational effects may already be important for masses 0.3 M Mars . The fraction of polluted WDs in our simulations, ~0.05, is consistent with observations of WDs with intermediate cooling times between ~0.1 and 1 Gyr. For cooling times 0.1 Gyr and 1 Gyr, our scenario cannot explain the high observed pollution fractions of up to 0.7. Nevertheless, our results motivate searches for companions around polluted WDs.

Description: We present high resolution observations of fine structures at pore boundaries. The inner part of granules towards umbra show dark striations which evolve into a filamentary structure with dark core and ‘Y’ shape at the head of the filaments. These filaments migrate into the umbra similar to penumbral filaments. These filaments show higher temperature, lower magnetic field strength and more inclined field compared to the background umbra. The optical depth stratification of physical quantities suggests their similarity with penumbral filaments. However, line-of-sight velocity pattern is different from penumbral filaments where they show downflows in the deeper layers of the atmosphere while the higher layers show upflows. These observations show filamentation in a simple magnetic configuration.

Description: A large number of supernova remnants (SNRs) in our Galaxy and galaxies nearby have been resolved in various radio bands. This radio emission is thought to be produced via synchrotron emission from electrons accelerated by the shock that the supernova ejecta drives into the external medium. Here we consider the sample of radio SNRs in the Magellanic Clouds. Given the size and radio flux of an SNR, we seek to constrain the fraction of shocked fluid energy in non-thermal electrons ( e ) and magnetic field ( B ), and find e B ~ 10 –3 . These estimates do not depend on the largely uncertain values of the external density and the age of the SNR. We develop a Monte Carlo scheme that reproduces the observed distribution of radio fluxes and sizes of the population of radio SNRs in the Magellanic Clouds. This simple model provides a framework that could potentially be applied to other galaxies with complete radio SNRs samples.

Description: We present a line survey of the ultraluminous infrared galaxy Arp 220, taken with the newly installed SEPIA (Swedish-European Southern Observatory PI receiver for APEX) Band 5 instrument on APEX (Atacama Pathfinder Experiment). We illustrate the capacity of SEPIA to detect the 183.3 GHz H 2 O 3 1,3 –2 2,0 line against the atmospheric H 2 O absorption feature. We confirm the previous detection of the HCN(2–1) line, and detect new transitions of standard dense gas tracers such as HNC(2–1), HCO + (2–1), CS(4–3), C 34 S(4–3) and HC 3 N(20–19). We also detect HCN(2–1) v 2 = 1 and the 193.5 GHz methanol (4–3) group for the first time. The absence of time variations in the megamaser water line compared to previous observations seems to rule out an AGN nuclear origin for the line. It could, on the contrary, favour a thermal origin instead, but also possibly be a sign that the megamaser emission is associated with star-forming cores washed out in the beam. We finally discuss how the new transitions of HCN, HNC and HCO + refine our knowledge of the interstellar medium physical conditions in Arp 220.

Description: We present and test a method that dramatically reduces variance arising from the sparse sampling of wavemodes in cosmological simulations. The method uses two simulations which are fixed (the initial Fourier mode amplitudes are fixed to the ensemble average power spectrum) and paired (with initial modes exactly out of phase). We measure the power spectrum, monopole and quadrupole redshift-space correlation functions, halo mass function and reduced bispectrum at z  = 1. By these measures, predictions from a fixed pair can be as precise on non-linear scales as an average over 50 traditional simulations. The fixing procedure introduces a non-Gaussian correction to the initial conditions; we give an analytic argument showing why the simulations are still able to predict the mean properties of the Gaussian ensemble. We anticipate that the method will drive down the computational time requirements for accurate large-scale explorations of galaxy bias and clustering statistics, and facilitating the use of numerical simulations in cosmological data interpretation.

Description: The ICH S6(R1) recommendations on safety evaluation of biotherapeutics have led to uncertainty in determining what would constitute a cause for concern that would require genotoxicity testing. A Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee Workgroup was formed to review the current practice of genotoxicity assessment of peptide/protein-related biotherapeutics. There are a number of properties of peptide/protein-related biotherapeutics that distinguish such products from traditional ‘small molecule’ drugs and need to be taken into consideration when assessing whether genotoxicity testing may be warranted and if so, how to do it appropriately. Case examples were provided by participating companies and decision trees were elaborated to determine whether and when genotoxicity evaluation is needed for peptides containing natural amino acids, non-natural amino acids and other chemical entities and for unconjugated and conjugated proteins. From a scientific point of view, there is no reason for testing peptides containing exclusively natural amino acids irrespective of the manufacturing process. If non-natural amino acids, organic linkers and other non-linker chemical components have already been tested for genotoxicity, there is no need to re-evaluate them when used in different peptide/protein-related biotherapeutics. Unless the peptides have been modified to be able to enter the cells, it is generally more appropriate to evaluate the peptides containing the non-natural amino acids and other non-linker chemical moieties in vivo where the cleavage products can be formed. For linkers, it is important to determine if exposure to reactive forms are likely to occur and from which origin. When the linkers are anticipated to be potential mutagenic impurities they should be evaluated according to ICH M7. If linkers are expected to be catabolic products, it is recommended to test the entire conjugate in vivo , as this would ensure that the relevant ‘free’ linker forms stemming from in vivo catabolism are tested.

Description: Genome sequences that contain tandem repeats of guanine can form stable four-stranded structures known as G-quadruplex, or G4 DNA. While the molecular mechanisms are not fully defined, such guanine-rich loci are prone to mutagenesis and recombination. Various repair pathways function to reduce the potential for genome instability by correcting base damage and replication errors; however, it is not yet fully defined how well these processes function at G4 DNA. One frequent form of base damage occurs from cytidine deamination, resulting in deoxyuracil and UG mismatches. In duplex and single-stranded DNA, uracil bases are recognised and excised by uracil glycosylases. Here, we tested the efficiency of uracil glycosylase activity in vitro on uracil bases located directly adjacent to guanine repeats and G4 DNA. We show that uracil excision by bacterial UDG and human hUNG2 is reduced at uracils positioned directly 5' or 3' of a guanine tetrad. Control reactions using oligonucleotides disrupted for G4 formation or reaction conditions that do not favour G4 formation resulted in full uracil excision activity. Based on these in vitro results, we suggest that folding of guanine-rich DNA into G4 DNA results in a DNA conformation that is resistant to uracil glycosylase-initiated repair and this has the potential to increase the risk of instability at guanine repeats in the genome.

Description: Galectin-4 is a member of the galectin family which consists of 15 galactoside-binding proteins. Previously, galectin-4 has been shown to have a role in cancer progression and metastasis and it is found upregulated in many solid tumours, including colorectal cancer (CRC). Recently, the role in the metastatic process was suggested to be via promoting cancer cells to adhere to blood vascular endothelium. In the present study, the regulatory region of LGALS4 (galectin-4) in seven colon cell lines was investigated with respect to genetic variation that could be linked to expression levels and therefore a tumourigenic effect. Interestingly, qRT-PCR and sequencing results revealed that galectin-4 upregulation is associated with SNPs rs116896264 and rs73933062. By use of luciferase reporter- and pull-down assays, we confirmed the association between the gene upregulation and the two SNPs. Also, using pull-down assay followed by mass spectrometry, we found that the presence rs116896264 and rs73933062 is changing transcription factors binding sites. In order to assess the frequencies of the two SNPs among colon cancer patients and healthy individuals, we genotyped 75 colon cancer patients, 12 patients with adenomatous polyposis and 17 patients with ulcerative colitis and we performed data mining in the 1000 genomes databank. We found the two SNPs co-occuring in 21% of 75 CRC patients, 0 out of 12 patients of adenomatous polyposis, and 6 out of 17 patients (35%) with ulcerative colitis. Both in the patient samples and in the 1000 genomes project, the two SNPs were found to co-occur whenever present (D' = 1).

Description: The dose effect between nucleoplasmic bridges (NPB) and relatively low doses of ionising radiation remains unknown. Accordingly, this study investigated the NPB frequencies in human peripheral blood lymphocytes exposed to low-dose 60 Co -rays. Complex anomalies, including fused nuclei (FUS), horse-shoe nuclei (HS) and circular nuclei (CIR), which possibly originated from multiple NPBs, were also scored. Human peripheral blood samples were collected from three healthy males and irradiated with 0–1 and 0–0.4 Gy 60 Co -rays. A cytokinesis-block micronucleus cytome assay was then conducted to analyse NPB, PFHC (NPB plus three complex nuclear anomalies) and micronucleus (MN) in binucleated cells. All dose–response curves followed the linear model for both NPB frequency and PFHC cell frequency. The dose–response curves between NPB frequency and absorbed dose at 0–1 and 0–0.4 Gy were y = 0.0037 x + 0.0005 ( R 2 = 0.979, P 〈 0.05) and y = 0.0043 x + 0.0004 ( R 2 = 0.941, P 〈 0.05), respectively. The dose–response curves between PFHC cell frequency and absorbed dose at 0–1 and 0–0.4 Gy were y = 0.0044 x + 0.0007 ( R 2 = 0.982, P 〈 0.05) and y = 0.0059 x + 0.0005 ( R 2 = 0.969, P 〈 0.05), respectively. The statistical significance of differences between the irradiated groups (0–0.4 Gy) and background levels of NPB, PFHC and MN were also analysed. The lowest analysable doses of NPB, PFHC and MN were 0.12, 0.08 and 0.08 Gy, respectively. In conclusion, NPBs and PFHC positively correlated with the absorbed radiation at a relatively low dose.

Description: The aim of the study was to investigate how coadministration of resveratrol (RSV) at different time after the start of irradiation influences the frequency of micronuclei (MN) in reticulocytes of bone marrow and peripheral blood, and if the RSV supplementation after termination of irradiation may influence the recovery process of damaged cells. Coadministration of RSV with 1-day delay after 1 Gy irradiation significantly decreased the levels of MN in bone marrow and in peripheral blood, whereas with 1-week delay, only in bone marrow reticulocytes. Above combined treatment did not improve the process of recovery. RSV supplementation with 1-day delay relatively to 0.5 Gy irradiation, significantly decreased the frequencies of MN, especially after coadministration with 28mg/kg bw of RSV. Coadministration of RSV since eighth day did not influence the frequencies of MN compared to irradiated cells. The recovery process in the presence of RSV proceeded faster. Supplementation of RSV following initiation of irradiation is beneficial in case of irradiation with lower doses. RSV should be supplemented as soon as possible. Supplementation of RSV after termination of irradiation significantly speed up the recovery. Current results confirmed the ability of RSV to mitigate the effect of irradiation.

Description: Various naturally occurring stilbene-like compounds that are related to resveratrol (RSV) possess some of the beneficial effects of the parent molecule and provide even further benefits. Therefore, a series of methoxylated analogues of RSV were prepared with the aim of increasing antitumour and proapoptotic activity. In a previous article, we studied two methoxy-derivatives, pterostilbene (PTERO) and trimethoxystilbene (TRIMETHOXY), in which the first was formed by the substitution of two hydroxyl groups with two methoxy groups ( trans -3,5-dimethoxy-4'-hydroxystilbene) and the second was formed by the replacement of all three OH groups with methoxy groups ( trans -3,5,4'-trimethoxystilbene). Both methoxy-derivatives showed stronger antioxidant activity when compared with RSV. In the present article, we focused on the analysis of the ability of RSV and its two methoxylated derivatives to protect proliferating non-tumoural cells from the damage induced by ionising radiation (IR). First we showed that the methoxy derivatives, contrary to their parental compound, are unable to affect topoisomerase enzyme and consequently are not clastogenic per se . Second we showed that both PTERO and TRIMETHOXY more efficiently reduce the chromosome damage induced by IR. Furthermore, TRIMETHOXY, but not PTERO, causes a delay in cell proliferation, particularly in mitosis progression increasing the number of cells in metaphase at the expense of prophases and ana/telophases.

Description: α-, β- and -asarone are naturally occurring phenylpropenes that occur in different plant families, mainly in Aristolochiaceae , Acoraceae and Lauraceae. Plants containing asarones are used as flavouring ingredients in alcoholic beverages (bitters), traditional phytomedicines and the rhizome of e.g. Acorus calamus is used to prepare tea. Although α- and β-asarone show a potential in the treatment of several diseases, previous studies have shown carcinogenicity in rodents (duodenum, liver). However, the mechanism of action remained unclear. Studies on the mutagenicity of propenylic α- and β-asarone are inconsistent and data on carcinogenicity and genotoxicity of allylic -asarone are lacking completely. Thus, the present study determined the mutagenicity of the three asarone isomers using the Ames fluctuation assay with and without exogenous metabolic activation (S9 mix) in the standard Salmonella typhimurium strains TA98 and TA100. A concentration dependent increase in mutagenicity could be verified for α- and β-asarone in strain TA100 in the presence of rat liver homogenate. The side-chain epoxides of α- and β-asarone, major metabolites formed in liver microsomes, caused mutations in TA100, supporting the hypothesis that epoxidation of the side chain plays a key role in mutagenicity of the propenylic alkenylbenzenes. The allylic -asarone, not undergoing detectable side-chain epoxidation in liver microsomes, was supposed to be activated via side-chain hydroxylation and further sulphonation, a typical pathway for other allylic alkenylbenzenes like estragole or methyleugenol. However, neither y-asarone nor 1'-OH--asarone showed any mutagenic effect even in the human SULT-expressing Salmonella strains (TA100-hSULT1A1 and TA100-hSULT1C2), while 1'-OH-methyleugenol used as a positive control was mutagenic under these conditions. These results indicate that the propenylic asarones are genotoxic via metabolic formation of side-chain epoxides while the side-chain hydroxylation/sulphonation pathway is either not operative or does not lead to mutagenicity with the allylic -asarone.

Description: Using a specialized technique sensitive to the presence of expanding ionized gas, we have detected a set of three concentric expanding shells in an H ii region in the nearby spiral galaxy M33. After mapping the kinematics in Hα with Fabry–Perot spectroscopy, we used slit spectra to measure the intensities of the [S ii ] doublet at 671.9, 673.1 nm and the [N ii ] doublet at 645.8, 658.3 nm to corroborate the kinematics and apply diagnostic tests using line ratios. These showed that the expanding shells are shock dominated as would be the case if they had originated with supernova explosions. Estimating their kinetic energies, we find fairly low values, indicating a fairly advanced stage of evolution. We obtain density, mass and parent star mass estimates, which, along with the kinetic energies, are inconsistent with the simplest models of shock–interstellar medium interaction. We propose that the presence and properties of an inhomogeneous medium offer a scenario which can account for these observations, and discuss the implications. Comparing our results with data from the literature supports the combined presence of an H ii region and supernova remnant material at the observed position.

Description: Prior to the downstream development of chemical substances, including pharmaceuticals and cosmetics, their influence on the genetic apparatus has to be tested. Several in vitro and in vivo assays have been developed to test for genotoxicity. In a first tier, a battery of two to three in vitro tests is recommended to cover mutagenicity, clastogenicity and aneugenicity as main endpoints. This regulatory in vitro test battery is known to have a high sensitivity, which is at the expense of the specificity. The high number of false positive in vitro results leads to excessive in vivo follow-up studies. In the case of cosmetics it may even induce the ban of the particular compound since in Europe the use of experimental animals is no longer allowed for cosmetics. In this article, an alternative approach to derisk a misleading positive Ames test is explored. Hereto we first tested the performance of five existing computational tools to predict the potential mutagenicity of a data set of 132 cosmetic compounds with a known genotoxicity profile. Furthermore, we present, as a proof-of-principle, a strategy in which a combination of computational tools and mechanistic information derived from in vitro transcriptomics analyses is used to derisk a misleading positive Ames test result. Our data shows that this strategy may represent a valuable tool in a weight-of-evidence approach to further evaluate a positive outcome in an Ames test.

Description: Pioglitazone (PTZ) is an oral antidiabetic agent whose anti-cancer properties have been described recently. Since PTZ increases the production of reactive oxygen species in mammalian cells, the aim of current study was to evaluate the cytotoxic, mutagenic and recombinogenic effects of PTZ using respectively the in vitro mitotic index assay and the in vitro mammalian cell micronucleus test in human peripheral lymphocytes, and the in vivo homozygotization assay in Aspergillus nidulans , which detects the loss of heterozygosity due to somatic recombination. Although the lowest PTZ concentrations (4–36 μM) did not show any significant rise in the micronucleus production, the higher PTZ concentration (108 μM) produced a statistically higher number of micronuclei than the negative control and significantly altered the cell-proliferation kinetics, demonstrating the mutagenic and antiproliferative effects of PTZ, respectively. The recombinogenic activity of PTZ, demonstrated here for the first time, was observed at the highest tested concentration (400 μM) through the homozygotization index rates significantly different from the negative control. Taken together, our results show that PTZ is genotoxic at a concentration higher than the therapeutic plasma concentration. This PTZ genotoxicity may be a potential benefit to its previously described antitumour activity.

Description: Environmental pollutants are complex mixtures in which metals are ubiquitous. Metal mixtures of arsenic, cadmium and lead are present in the occupational environment and generate health effects such as cardiovascular, renal and cancer diseases. Cell transformation induced by metal mixtures that depend on reactive oxygen species (ROS) generation, cell viability maintenance and avoidance of senescence was previously reported by our group. The aim of the present study was to explore the role of a Obg-like ATPase1 (OLA1) in the cell transformation of BALB/c 3T3 A31-1-1 clonal cells induced by a metal mixture (2 µM NaAsO 2 , 2 µM CdCl 2 and 5 µM Pb(C 2 H 3 O 2 ) 2 . 3H 2 O) through ROS generation. The interest in OLA1 is justified because this protein has been proposed to be a negative regulator of the cellular antioxidant response. Small interfering RNA (siRNA) was used to knockdown OLA1 before the initiation stage of the transformation assay. We evaluated (ROS) and OLA1 protein expression throughout the initiation and promotion stages of transformation. OLA1 knockdown modulated metal mixture-induced cell transformation more strongly when the metal mixture was an initiator stimulus than when it was a promoter. The ability of the metal mixture to initiate cell transformation was diminished by OLA1 knockdown, an effect that depended on intracellular ROS levels. The effect of OLA1 was synergistic with N -Acetyl- l -cysteine (NAC) co-treatment. Oxidative stress-associated transcription factors Egr1 and Smad were also down-regulated by the OLA1 knockdown, contributing to the rescue of metal mixture cell transformation.

Description: G-quadruplexes (G4) are highly stable tetra-stranded DNA secondary structures known to mediate gene regulation and to trigger genomic instability events during replication. G4 structural stability can be affected by DNA methylation and oxidation modifications; thus nutrients such as folate that have the ability to alter these processes could potentially modify the genomic occurrence of G4 elements. Hela cells were cultured in a range of folate concentrations or in the presence or absence of 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor. G4 structures were then quantified by immunofluorescence using an automated quantitative imaging system. G4 frequency in Hela cells and nuclei area mean were increased in 20nM folate medium compared with 2000nM folate, as well as in the presence of 5-aza-2'-deoxycytidine when compared to cells non-exposed to 5-aza-2'-deoxycytidine. These changes were exacerbated when pyridostatin, a G4 stabilising ligand, was added to the culture medium. G4 intensity in Hela cells cultured in deficient folate condition with pyridostatin was highly correlated with DNA damage as measured by H2AX immunofluorescence ( r = 0.71). This study showed for the first time that cellular G4 balance is modifiable by low folate concentrations and that these changes may occur as a consequence of DNA hypomethylation. Although the exact mechanism by which these changes occur is unclear, these findings establish the possibility that nutrients could be utilised as a tool for sustaining genome integrity by modifying G4 frequency at a cellular level.

Description: Metal oxide nanoparticles (NPs), including zinc oxide (ZnO) NPs have shown success for use as vehicles for drug delivery and targeting gene delivery in many diseases like cancer. Current anticancer chemotherapeutics fail to effectively differentiate between cancerous and normal cells. There is an urgent need to develop novel drug delivery system that can better target cancer cells while sparing normal cells and tissues. Particularly, ZnO NPs exhibit a high degree of cancer cell selectivity and induce cell death, oxidative stress, interference with the cell cycle progression and genotoxicity in cancerous cells. In this scenario, effective cellular uptake of NP seems to be crucial, which is shown to be affected by cell cycle progression. In the present study, the cytotoxic potential of ZnO NPs and the effect of different cell cycle phases on the uptake of ZnO NPs were examined in A431 cells. It is shown that the ZnO NPs led to cell death and reactive oxygen species generation and were able to induce cell cycle arrest in S and G 2 /M phase with the higher uptake in G 2 /M phase compared with other phases.

Description: Malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, is a mutagenic and carcinogenic compound that can react with DNA to form several types of DNA adducts including the deoxyguanosine adduct (M 1 dG). The aim of this cross-sectional study was to evaluate the association between individual dietary and lifestyle habits and M 1 dG levels, measured in peripheral leukocytes in a large representative sample of the general population of Florence City (Italy). Selected anthropometric measurements, detailed information on dietary and lifestyle habits and blood samples were available for 313 adults of the Florence City Sample enrolled in the frame of European Prospective Investigation into Cancer and nutrition (EPIC) study. A multivariate regression analysis adjusted for selected individual characteristics possibly related to M 1 dG levels (sex, age, BMI, smoke, physical activity level, education level, total caloric intake and a Mediterranean dietary score) was performed to estimate the association between these parameters and M 1 dG levels. M 1 dG levels were significantly higher in women ( P = 0.014) and lower in moderately active or active subjects ( P = 0.037).We also found a significant inverse association with the Modified Mediterranean dietary score ( P for trend = 0.049), particularly evident for the highest categories of adherence. Our results indicate that M 1 dG levels can be modulated by selected individual characteristics such as gender, physical activity and a Mediterranean dietary pattern.

Description: We study the origin of the stellar α-element-to-iron abundance ratio, [α/Fe] * , of present-day central galaxies, using cosmological, hydrodynamical simulations from the Evolution and Assembly of GaLaxies and their Environments (EAGLE) project. For galaxies with stellar masses of M * 〉 10 10.5 M , [α/Fe] * increases with increasing galaxy stellar mass and age. These trends are in good agreement with observations of early-type galaxies, and are consistent with a ‘downsizing’ galaxy formation scenario: more massive galaxies have formed the bulk of their stars earlier and more rapidly, hence from an interstellar medium that was mostly α-enriched by massive stars. In the absence of feedback from active galactic nuclei (AGNs), however, [α/Fe] * in M * 〉 10 10.5 M galaxies is roughly constant with stellar mass and decreases with mean stellar age, extending the trends found for lower mass galaxies in both simulations with and without AGN. We conclude that AGN feedback can account for the α-enhancement of massive galaxies, as it suppresses their star formation, quenching more massive galaxies at earlier times, thereby preventing the iron from longer lived intermediate-mass stars (supernova Type Ia) from being incorporated into younger stars.

Description: We report broad-band spectral properties of the high-mass X-ray binary pulsar SMC X-2 by using three simultaneous Nuclear Spectroscopy Telescope Array and Swift /XRT observations during its 2015 outburst. The pulsar was significantly bright, reaching a luminosity up to as high as ~5.5 x 10 38 erg s –1 in 1–70 keV range. Spin period of the pulsar was estimated to be 2.37 s. Pulse profiles were found to be strongly luminosity dependent. The 1–70 keV energy spectrum of the pulsar was well described with three different continuum models such as (i) negative and positive power law with exponential cutoff, (ii) Fermi -Dirac cutoff power law and (iii) cutoff power-law models. Apart from the presence of an iron line at ~6.4 keV, a model independent absorption like feature at ~27 keV was detected in the pulsar spectrum. This feature was identified as a cyclotron absorption line and detected for the first time in this pulsar. Corresponding magnetic field of the neutron star was estimated to be ~2.3 x 10 12  G. The cyclotron line energy showed a marginal negative dependence on the luminosity. The cyclotron line parameters were found to be variable with pulse phase and interpreted as due to the effect of emission geometry or complicated structure of the pulsar magnetic field.

Description: We analyse structural decompositions of 500 late-type galaxies (Hubble T -type ≥6) from the Spitzer Survey of Stellar Structure in Galaxies ( S 4 G ; Salo et al.), spanning stellar mass range of about 10 7 to a few times 10 10 M . Their decomposition parameters are compared with those of the early-type dwarfs in the Virgo cluster from Janz et al. They have morphological similarities, including the fact that the fraction of simple one-component galaxies in both samples increases towards lower galaxy masses. We find that in the late-type two-component galaxies both the inner and outer structures are by a factor of 2 larger than in the early-type dwarfs, for the same stellar mass of the component. While dividing the late-type galaxies to low- and high-density environmental bins, it is noticeable that both the inner and outer components of late types in the high local density galaxies are smaller, and lie closer in size to those of the early-type dwarfs. This suggests that, although structural differences between the late- and early-type dwarfs are observed, environmental processes can plausibly transform their sizes sufficiently, thus linking them evolutionarily.

Description: We calculate the microlensing event rate and typical time-scales for the free-floating planet (FFP) population that is predicted by the core accretion theory of planet formation. The event rate is found to be ~1.8  x  10 –3 of that for the stellar population. While the stellar microlensing event time-scale peaks at around 20 d, the median time-scale for FFP events (~0.1 d) is much shorter. Our values for the event rate and the median time-scale are significantly smaller than those required to explain the Sumi et al. result, by factors of ~13 and ~16, respectively. The inclusion of planets at wide separations does not change the results significantly. This discrepancy may be too significant for standard versions of both the core accretion theory and the gravitational instability model to explain satisfactorily. Therefore, either a modification to the planet formation theory is required or other explanations to the excess of short-time-scale microlensing events are needed. Our predictions can be tested by ongoing microlensing experiment such as Korean Microlensing Telescope Network, and by future satellite missions such as WFIRST and Euclid .

Description: The recent discovery of three Earth-sized, potentially habitable planets around a nearby cool star, TRAPPIST-1, has provided three key targets for the upcoming James Webb Space Telescope (JWST) . Depending on their atmospheric characteristics and precise orbit configurations, it is possible that any of the three planets may be in the liquid water habitable zone, meaning that they may be capable of supporting life. We find that present-day Earth levels of ozone, if present, would be detectable if JWST observes 60 transits for innermost planet 1b and 30 transits for 1c and 1d.

Description: The Advanced Laser Interferometer Gravitational-Wave Observatory (ALIGO) observatory recently reported the first direct detection of gravitational waves (GW) which triggered ALIGO on 2015 September 14. We report on observations taken with the Swift satellite two days after the trigger. No new X-ray, optical, UV or hard X-ray sources were detected in our observations, which were focused on nearby galaxies in the GW error region and covered 4.7 deg 2 (~2 per cent of the probability in the rapidly available GW error region; 0.3 per cent of the probability from the final GW error region, which was produced several months after the trigger). We describe the rapid Swift response and automated analysis of the X-ray telescope and UV/Optical telescope data, and note the importance to electromagnetic follow-up of early notification of the progenitor details inferred from GW analysis.

Description: Superluminous supernovae (SLSNe) have been suggested to be powered by strongly magnetized, rapidly rotating neutron stars which are often called magnetars. In this process, rotational energy of the magnetar is radiated via magnetic dipole radiation and heats the supernova ejecta. However, if magnetars are highly distorted in their geometric shape, rotational energy is mainly lost as gravitational wave radiation and thus such magnetars cannot power SLSNe. By simply comparing electromagnetic and gravitational wave emission time-scales, we constrain upper limits to the ellipticity of magnetars by assuming that they power the observed SLSNe. We find that their ellipticity typically needs to be less than about a few 10 –3 . This indicates that the toroidal magnetic field strengths in these magnetars are typically less than a few 10 16 G so that their distortions remain small. Because light-curve modelling of SLSNe shows that their dipole magnetic field strengths are of the order of 10 14 G, the ratio of poloidal to toroidal magnetic field strengths is found to be larger than ~0.01 in magnetars powering SLSNe.

Description: We present Gemini Multi-Object Spectrograph (GMOS) imaging of 12 candidate intergalactic globular clusters (IGCs) in the Local Group, identified in a recent survey of the Sloan Digital Sky Survey (SDSS) footprint by di Tullio Zinn & Zinn. Our image quality is sufficiently high, at ~0.4–0.7 arcsec, that we are able to unambiguously classify all 12 targets as distant galaxies. To reinforce this conclusion we use GMOS images of globular clusters in the M31 halo, taken under very similar conditions, to show that any genuine clusters in the putative IGC sample would be straightforward to distinguish. Based on the stated sensitivity of the di Tullio Zinn & Zinn search algorithm, we conclude that there cannot be a significant number of IGCs with M V ≤ –6 lying unseen in the SDSS area if their properties mirror those of globular clusters in the outskirts of M31 – even a population of 4 would have only a 1 per cent chance of non-detection.

Description: The R h  =  ct cosmological model has received considerable attention in recent years owing to claims that it is favoured over the standard cold dark mater (CDM) model by most observational data. A key feature of the R h  =  ct model is that the zero active mass condition  + 3 p  = 0 holds at all epochs. Most recently, Melia has claimed that this condition is a requirement of the symmetries of the Friedmann–Robertson–Walker spacetime. We demonstrate that this claim is false and results from a flaw in the logic of Melia's argument.

Description: We investigate the prospects for the capture of the proposed Planet 9 from other stars in the Sun's birth cluster. Any capture scenario must satisfy three conditions: the encounter must be more distant than ~150 au to avoid perturbing the Kuiper belt; the other star must have a wide-orbit planet ( a 100 au); the planet must be captured on to an appropriate orbit to sculpt the orbital distribution of wide-orbit Solar system bodies. Here we use N -body simulations to show that these criteria may be simultaneously satisfied. In a few per cent of slow close encounters in a cluster, bodies are captured on to heliocentric, Planet 9-like orbits. During the ~100 Myr cluster phase, many stars are likely to host planets on highly eccentric orbits with apastron distances beyond 100 au if Neptune-sized planets are common and susceptible to planet–planet scattering. While the existence of Planet 9 remains unproven, we consider capture from one of the Sun's young brethren a plausible route to explain such an object's orbit. Capture appears to predict a large population of trans-Neptunian objects (TNOs) whose orbits are aligned with the captured planet, and we propose that different formation mechanisms will be distinguishable based on their imprint on the distribution of TNOs.

Description: We explore the formation of massive high-redshift Population III (Pop III) galaxies through photoionization feedback. We consider dark matter haloes formed from progenitors that have undergone no star formation as a result of early reionization and photoevaporation caused by a nearby galaxy. Once such a halo reaches 10 9 M , corresponding to the Jeans mass of the photoheated intergalactic medium at z 7, pristine gas is able to collapse into the halo, potentially producing a massive Pop III starburst. We suggest that this scenario may explain the recent observation of strong He  ii 1640 Å line emission in CR 7, which is consistent with ~10 7 M of young Pop III stars. Such a large mass of Pop III stars is unlikely without the photoionization feedback scenario, because star formation is expected to inject metals into haloes above the atomic cooling threshold (~10 8 M at z 7). We use merger trees to analytically estimate the abundance of observable Pop III galaxies formed through this channel, and find a number density of 10 –7 Mpc –3 at z  = 6.6 (the redshift of CR 7). This is approximately a factor of 10 lower than the density of Ly α emitters as bright as CR 7.

Description: In this Letter we investigate the effect of boxy/peanut (b/p) bulges on bar-induced gas inflow to the central kiloparsec, which plays a crucial role on the evolution of disc galaxies. We carry out hydrodynamic gas response simulations in realistic barred galaxy potentials, including or not the geometry of a b/p bulge, to investigate the amount of gas inflow induced in the different models. We find that b/p bulges can reduce the gas inflow rate to the central kiloparsec by more than an order of magnitude, which leads to a reduction in the amount of gas available in the central regions. We also investigate the effect of the dark matter halo concentration on these results, and find that for maximal discs, the effect of b/p bulges on gas inflow remains significant. The reduced amount of gas reaching the central regions due to the presence of b/p bulges could have significant repercussions on the formation of discy- (pseudo-) bulges, on the amount of nuclear star formation and feedback, on the fuel reservoir for AGN activity, and on the overall secular evolution of the galaxy.

Description: We present a proof-of-concept study of a method to estimate the inclination angle of compact high velocity clouds (CHVCs), i.e. the angle between a CHVC's trajectory and the line of sight. The inclination angle is derived from the CHVC's morphology and kinematics. We calibrate the method with numerical simulations, and we apply it to a sample of CHVCs drawn from HIPASS (Putman et al.). Implications for CHVC distances are discussed.

Description: The optical/ultraviolet (UV) variability of quasars has been discovered to be correlated with other quasar properties, such as luminosity, black hole mass and rest-frame wavelength. However, the origin of variability has been a puzzle so far. In this work, we upgrade the accretion disc model, which assumed the variability is caused by the change of global mass accretion rate, by constraining the disc size to match the viscous time-scale of accretion disc to the variability time-scale observed and by including the irradiation/X-ray reprocessing to make the emitted spectrum become steeper. We find this hybrid model can reproduce the observed bluer-when-brighter trend quite well, which is used to validate the theoretical model by several works recently. The traditional correlation between the variability amplitude and rest-frame wavelength can also be well fitted by our model. In addition, a weak positive correlation between variability amplitude and black hole mass is present, qualitatively consistent with recent observations.

Description: The first-known tidal disruption event (TDE) with strong evidence for a relativistic jet – based on extensive multiwavelength campaigns – is Swift J1644+5734. In order to directly measure the apparent speed of the radio jet, we performed very long baseline interferometry (VLBI) observations with the European VLBI network (EVN) at 5 GHz. Our observing strategy was to identify a very nearby and compact radio source with the real-time e-EVN, and then utilize this source as a stationary astrometry reference point in the later five deep EVN observations. With respect to the in-beam source FIRST J1644+5736, we have achieved a statistical astrometric precision about 12 μas (68 per cent confidence level) per epoch. This is one of the best phase-referencing measurements available to date. No proper motion has been detected in the Swift J1644+5734 radio ejecta. We conclude that the apparent average ejection speed between 2012.2 and 2015.2 was less than 0.3 c with a confidence level of 99 per cent. This tight limit is direct observational evidence for either a very small viewing angle or a strong jet deceleration due to interactions with a dense circum-nuclear medium, in agreement with some recent theoretical studies.

Description: Near-field cosmology – using detailed observations of the Local Group and its environs to study wide-ranging questions in galaxy formation and dark matter physics – has become a mature and rich field over the past decade. There are lingering concerns, however, that the relatively small size of the present-day Local Group (~2 Mpc diameter) imposes insurmountable sample-variance uncertainties, limiting its broader utility. We consider the region spanned by the Local Group's progenitors at earlier times and show that it reaches 3 arcmin 7 comoving Mpc in linear size (a volume of 350 Mpc 3 ) at z  = 7. This size at early cosmic epochs is large enough to be representative in terms of the matter density and counts of dark matter haloes with M vir ( z = 7) 2 x 10 9 M . The Local Group's stellar fossil record traces the cosmic evolution of galaxies with 10 3 M * ( z = 0)/M 10 9 (reaching M 1500  〉 –9 at z  ~ 7) over a region that is comparable to or larger than the Hubble Ultra-Deep Field (HUDF) for the entire history of the Universe. In the JWST era, resolved stellar populations will probe regions larger than the HUDF and any deep JWST fields, further enhancing the value of near-field cosmology.

Description: The presence or lack of eclipses in the X-ray light curves of ultraluminous X-ray sources (ULXs) can be directly linked to the accreting system geometry. In the case where the compact object is stellar mass and radiates isotropically, we should expect eclipses by a main-sequence to sub-giant secondary star on the recurrence time-scale of hours to days. X-ray light curves are now available for large numbers of ULXs as a result of the latest XMM–Newton catalogue. We determine the amount of fractional variability that should be injected into an otherwise featureless light curve for a given set of system parameters as a result of eclipses and compare this to the available data. We find that the vast majority of sources for which the variability has been measured to be non-zero and for which available observations meet the criteria for eclipse searches, have fractional variabilities which are too low to derive from eclipses and so must be viewed such that ≤ cos – 1 ( R * / a ). This would require that the disc subtends a larger angle than that of the secondary star and is therefore consistent with a conical outflow formed from super-critical accretion rates and implies some level of geometrical beaming in ULXs.

Description: We show that for the undisturbed interstellar velocity vector $\boldsymbol {V}_{\rm IS}$ and magnetic field direction $\boldsymbol {B}_{\rm IS}$ defined by IBEX ( Interstellar Boundary Explorer ) Ribbon centre, the radial direction of Voyager 2 over the last decade, and the (thermal proton) plasma velocity measured by the spacecraft since 2010.5, are almost parallel to the ( $\boldsymbol {B}_{\rm IS}$ , $\boldsymbol {V}_{\rm IS}$ )-plane, which coincides in practice with the hydrogen deflection plane. In consequence the plasma flow velocity measured by Voyager 2 in the inner heliosheath rotates more in the transverse than in the polar direction (explanation alternative to McComas & Schwadron). Note that the ( $\boldsymbol {B}_{\rm IS}$ , $\boldsymbol {V}_{\rm IS}$ ) plane is a symmetry plane of the interstellar plasma flow at large heliocentric distances.

Description: Coronal-Line Forest Active Galactic Nuclei (CLiF AGN) are remarkable in the sense that they have a rich spectrum of dozens of coronal emission lines (e.g. [Fe vii ], [Fe x ] and [Ne v ]) in their spectra. Rose, Elvis & Tadhunter suggest that the inner obscuring torus wall is the most likely location of the coronal line region in CLiF AGN, and the unusual strength of the forbidden high-ionization lines is due to a specific AGN-torus inclination angle. Here, we test this suggestion using mid-IR colours (4.6–22 μm) from the Wide-Field Infrared Survey Explorer for the CLiF AGN. We use the Fischer et al. result that showed that as the AGN-torus inclination becomes more face on, the Spitzer 5.5–30 μm colours become bluer. We show that the [ W 2– W 4] colours for the CLiF AGN (〈[ W 2– W 4]〉 = 5.92 ± 0.12) are intermediate between Sloan Digital Sky Survey (SDSS) type 1 (〈[ W 2– W 4]〉 = 5.22 ± 0.01) and type 2 AGN (〈[ W 2– W 4]〉 = 6.35 ± 0.03). This implies that the AGN-torus inclinations for the CLiF AGN are indeed intermediate, supporting the work of Rose, Elvis & Tadhunter. The confirmed relation between CLiF AGN and their viewing angle shows that CLiF AGN may be useful for our understanding of AGN unification.

Description: We present the discovery of two z  〉 6 quasars, selected as i -band dropouts in the Very Large Telescope Survey Telescope ATLAS survey. Our first quasar has redshift, z  = 6.31 ± 0.03, z -band magnitude, z AB  = 19.63 ± 0.08 and rest frame 1450 Å absolute magnitude, M 1450  = –27.8 ± 0.2, making it the joint second most luminous quasar known at z  〉 6. The second quasar has z  = 6.02 ± 0.03, z AB  = 19.54 ± 0.08 and M 1450  = –27.0 ± 0.1. We also recover a z  = 5.86 quasar discovered by Venemans et al., in preparation. To select our quasars, we use a new 3D colour space, combining the atlas optical colours with mid-infrared data from the Wide-field Infrared Survey Explorer . We use i AB – z AB colour to exclude main-sequence stars, galaxies and lower redshift quasars, W 1 – W 2 to exclude L dwarfs and z AB – W 2 to exclude T dwarfs. A restrictive set of colour cuts returns only our three high redshift quasars and no contaminants, albeit with a sample completeness of ~50 per cent. We discuss how our 3D colour space can be used to reject the majority of contaminants from samples of bright 5.7 〈 z  〈 6.3 quasars, replacing follow-up near-infrared photometry, whilst retaining high completeness.

Description: I present an exact and explicit solution to the scalar (Stokes flux intensity) radio interferometer imaging equation on a spherical surface which is valid also for non-coplanar interferometer configurations. This imaging equation is comparable to w -term imaging algorithms, but by using a spherical rather than a Cartesian formulation this term has no special significance. The solution presented also allows direct identification of the scalar (spin 0 weighted) spherical harmonics on the sky. The method should be of interest for future multispacecraft interferometers, wide-field imaging with non-coplanar arrays, and cosmic microwave background spherical harmonic measurements using interferometers.

Description: We present Atacama Large Millimeter/submillimeter Array observations of 99.02 GHz free–free and H40α emission from the centre of the nearby starburst galaxy NGC 253. We calculate electron temperatures of 3700–4500 K for the photoionized gas, which agrees with previous measurements. We measure a photoionizing photon production rate of (3.2 ± 0.2) 10 53  s –1 and a star formation rate of 1.73 ± 0.12 M  yr –1 within the central 20 10 arcsec, which fall within the broad range of measurements from previous millimetre and radio observations but which are better constrained. We also demonstrate that the dust opacities are ~3 dex higher than inferred from previous near-infrared data, which illustrates the benefits of using millimetre star formation tracers in very dusty sources.

Description: We analyse the distinguishability of populations of coalescing binary neutron stars, neutron-star black hole binaries, and binary black holes, whose gravitational-wave signatures are expected to be observed by the advanced network of ground-based interferometers LIGO and Virgo. We consider population-synthesis predictions for plausible merging binary distributions in mass space, along with measurement accuracy estimates from the main gravitational-wave parameter-estimation pipeline. We find that for our model compact-object binary mass distribution, we can always distinguish binary neutron stars and black hole–neutron-star binaries, but not necessarily black hole–neutron-star binaries and binary black holes; however, with a few tens of detections, we can accurately identify the three subpopulations and measure their respective rates.

Description: Determination of the mode of action of carcinogenic agents is an important factor in risk assessment and regulatory practice. To assess the ability of the erythrocyte-based Pig-a mutation assay to discriminate between genotoxic and non-genotoxic modes of action, the mutagenic response of Sprague Dawley rats exposed to methyl carbamate (MC) or ethyl carbamate (EC) was investigated. EC, a potent carcinogen, is believed to induce DNA damage through the formation of a DNA-reactive epoxide group, whereas the closely structurally related compound, MC, cannot form this epoxide and its weaker carcinogenic activity is thought to be secondary to inflammation and promotion of cell proliferation. The frequency of Pig-a mutant phenotype cells was monitored before, during, and after 28 consecutive days of oral gavage exposure to either MC (doses ranging from 125 to 500mg/kg/day) or EC (250mg/kg/day). Significant increases in the frequency of mutant reticulocytes were observed from Days 15 through 43, with a peak mean frequency of 19.9 x 10 –6 on Day 29 (i.e. 24.9-fold increase relative to mean vehicle control across all four sampling times). As expected, mutant erythrocyte responses lagged behind mutant reticulocyte responses, with a maximal mean frequency of 8.2 x 10 –6 on Day 43 (i.e. 16.4-fold increase). No mutagenic effects were observed with MC. A second indicator of in vivo genotoxicity, peripheral blood micronucleated reticulocytes, was also studied. This endpoint was responsive to EC (3.3-fold mean increase), but not to MC. These results support the hypothesis that genotoxicity contributes to the carcinogenicity of EC but not of MC, and illustrates the value of the Pig-a assay for discriminating between genotoxic and non-genotoxic modes of action.

Description: As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RET CD59– and RBC CD59– , respectively) in peripheral blood of male Sprague Dawley ® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RET CD59– and RBC CD59– (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies.

Description: The Pig-a assay has shown promise as a regulatory assay for evaluating in vivo gene mutation. A recent International Workshop on Genotoxicity Testing workgroup discussed the state of the assay and identified several knowledge gaps in assay development. This Mutagenesis Special Topic includes a collection of reports that addresses some of these knowledge gaps, including identifying the mutations responsible for the Pig-a mutant phenotype, the effect of sex on the response, probing the robustness of the assay and expanding the number of agents tested in the assay, especially agents expected to yield negative responses.

Description: The Pig-a assay has rapidly gained international interest as a useful tool for assessing the mutagenic potential of compounds in vivo . Although a large number of compounds, including both mutagens and non-mutagens, have been tested in the rat Pig-a assay in haematopoietic cells, there is limited understanding of how perturbations in haematopoiesis affect assay performance. Of particular concern is the possibility that regenerative haematopoiesis alone, without exposure to a genotoxic agent, could result in elevated Pig-a mutant cell frequencies. To address this concern, Wistar-Han rats were dosed by oral gavage with a non-genotoxic haemolytic agent, 2-butoxyethanol (2-BE). Dose levels ranging from 0 to 450mg/kg were tested using both single administration and 28-day treatment regimens. Haematology parameters were assessed at minimum within the first 24h of treatment and 8 days after the final administration. Pig-a mutant frequencies were assessed on Days 15 and ~30 for both treatment protocols and also on Days 43 and 57 for the 28-day protocol. Even at doses of 2-BE that induced marked intravascular lysis and strong compensatory erythropoiesis, the average Pig-a mutant phenotype red blood cell and reticulocyte frequencies were within the historical vehicle control distribution. 2-BE therefore showed no evidence of in vivo mutagenicity in these studies. The data suggest that perturbations in haematopoiesis alone do not lead to an observation of increased mutant frequency in the Pig-a assay.

Description: The Pig-a assay is used for monitoring somatic cell mutation in laboratory animals and humans. The assay detects haematopoietic cells deficient in glycosylphosphatidylinositol (GPI)-anchored protein surface markers using flow cytometry. However, given that synthesis of the protein markers (and the expression of their genes) is independent of the expression of the X-linked Pig-a gene and the function of its enzyme product, the deficiency of markers at the surface of the cells may be caused by a number of events (e.g. by mutation or epigenetic silencing in the marker gene itself or in any of about two dozen autosomal genes involved in the synthesis of GPI). Here we provide direct evidence that the deficiency of the GPI-anchored surface marker CD48 in rat T-cells is accompanied by mutation in the endogenous X-linked Pig-a gene. We treated male F344 rats with N -ethyl- N -nitrosourea (ENU), and established colonies from flow cytometry-identified and sorted CD48-deficient spleen T-lymphocytes. Molecular analysis confirmed that the expanded sorted cells have mutations in the Pig-a gene. The spectrum of Pig-a mutation in our model was consistent with the spectrum of ENU-induced mutation determined in other in vivo models, mostly base-pair substitutions at A:T with the mutated T on the non-transcribed strand of Pig-a genomic DNA. We also used next generation sequencing to derive a similar mutational spectrum from a pool of 64 clones developed from flow-sorted CD48-deficient lymphocytes. Our findings confirm that Pig-a assays detect what they are designed to detect—gene mutation in the Pig-a gene.

Description: Validation of the Pig-a gene mutation assay has been based mainly on studies in male rodents. To determine if the mutagen-induced responses of the X-linked Pig-a gene differ in females compared to males, 7- or 14-week old male and female Sprague Dawley rats were exposed to N -ethyl- N -nitrosourea (ENU). In the study with the 7-week old rats, exposure was to 0, 1, 5 or 25mg ENU/kg/day for three consecutive days (study Days 1–3). Pig-a mutant phenotype reticulocyte (RET CD59– ) and mutant phenotype erythrocyte (RBC CD59– ) frequencies were determined on study Days –4, 15, 29 and 46 using immunomagnetic separation in conjunction with flow cytometric analysis ( In Vivo MutaFlow ® ). Additionally, blood samples collected on Day 4 were analysed for micronucleated reticulocyte (MN-RET) frequency ( In Vivo MicroFlow ® ). The percentage of reticulocytes (%RET) was markedly higher in the 7-week old males compared to females through Day 15 (2.39-fold higher on Day –4). At 25mg/kg/day, ENU reduced Day 4 RET frequencies in both sexes, and the two highest dose levels resulted in elevated MN-RET frequencies, with no sex or treatment x sex interaction. The two highest dose levels significantly elevated the frequencies of mean RET CD59– and RBC CD59– in both sexes from Day 15 onward. RET CD59– and RBC CD59– frequencies were somewhat lower for females compared to males at the highest dose level studied, and differences in RET CD59– resulted in a statistically significant interaction effect of treatment x sex. In the study with 14-week old rats, treatment was for 3 days with 0 or 25mg ENU/kg/day. RET frequencies differed to a lesser degree between the sexes, and in this case there was no evidence of a treatment x sex interaction. These results suggest that the slightly higher response in younger males than in the younger females may be related to differences in erythropoiesis function at that age. In conclusion, while some quantitative differences were noted, there were no qualitative differences in how males and females responded to a prototypical mutagen, and support the contention that both sexes are equally acceptable for Pig-a gene mutation studies.

Description: Isothiocyanates are plant-derived compounds that may be beneficial in the prevention of certain chronic diseases. Yet, by stimulating the production of reactive oxygen species (ROS), isothiocyanates can be genotoxic. Whether antioxidants influence isothiocyanate-induced genotoxicity is unclear, but this situation was clarified appreciably herein. In HCT116 cells, phenethyl isothiocyanate (PEITC) increased ROS production, which was inhibited by N -acetylcysteine (NAC) and deferoxamine (DFO) but not by ascorbic acid (ASC) and trolox (TRX) that were found to be more potent radical scavengers. Surprisingly, ASC and TRX each intensified the DNA damage that was caused by PEITC, but neither ASC nor TRX by themselves caused any DNA damage. In contrast, NAC and DFO each not only attenuated PEITC-induced DNA damage but also attenuated the antioxidant-intensified, PEITC-induced DNA damage. To determine if the DNA damage could be related to possible changes in the major antioxidant defence system, glutathione (GSH) was investigated. PEITC lowered GSH levels, which was prevented by NAC, whereas ASC, TRX and DFO neither inhibited nor enhanced the GSH-lowering effect of PEITC. The GSH synthesis inhibitor, buthionine sulphoxime, intensified PEITC-induced DNA damage, although by itself buthionine sulphoxime did not directly cause DNA damage. The principal findings suggest that ASC and TRX make PEITC more genotoxic, which might be exploited in killing cancer cells as one approach in killing cancer cells is to extensively damage their DNA so as to initiate apoptosis.

Description: The mycotoxin aflatoxin B 1 (AFB 1 ) may initiate cancer by causing oxidatively damaged DNA, specifically by causing 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) lesions. Base excision repair removes these lesions, with 8-oxoguanine glycosylase (OGG1) being the rate-limiting enzyme. The aim of this study was to determine the effect of ogg1 deficiency on AFB 1 -induced oxidatively damaged DNA and tumourigenesis. Female wild-type, heterozygous and homozygous ogg1 null mice were given a single dose of 50mg/kg AFB 1 or 40 µl dimethyl sulfoxide (DMSO) ip. Neither ogg1 genotype nor AFB 1 treatment affected levels of oxidised guanine in lung or liver 2h post-treatment. AFB 1 -treated ogg1 null mice showed exacerbated weight loss and mortality relative to DMSO-treated ogg1 null mice, but AFB 1 treatment did not significantly increase lung or liver tumour incidence compared with controls, regardless of ogg1 genotype. Suspect lung masses from three of the AFB 1 -treated mice were adenomas, and masses from two of the mice were osteosarcomas. No osteosarcomas were observed in DMSO-treated mice. All liver masses from AFB 1 -treated mice were adenomas, and one also contained a hepatocellular carcinoma. In DNA from the lung tumours, the K- ras mutation pattern was inconsistent with initiation by AFB 1 . In conclusion, ogg1 status did not have a significant effect on AFB 1 -induced oxidatively damaged DNA or tumourigenesis, but deletion of one or both alleles of ogg1 did increase susceptibility to other aspects of AFB 1 toxicity.

Description: Integration of in vivo genotoxicity testing into standard toxicology studies presents multiple advantages as it reduces animal use and costs, accelerates data generation and provides concurrent data that are useful for interpreting results. The in vivo Pig-a assay is a mammalian gene mutation assay that utilises peripheral blood and thus has a high integration potential. Although inter-laboratory reproducibility has been well demonstrated, further characterisation is required for this assay. In this study, we evaluated intra-laboratory reproducibility of the in vivo Pig-a gene mutation assay (MutaFlow® kit) in rats through the conduct of an assay characterisation prior to subsequent use in Good Laboratory Practices (GLP) toxicology studies. To evaluate intra-laboratory reproducibility, intra-assay and inter-assay variability, ruggedness, robustness and blood storage stability were assessed. These assessments were performed using blood obtained from male Sprague–Dawley rats exposed to 0, 20 or 40mg/kg/day N -ethyl- N -nitrosourea via oral gavage for three consecutive days. Blood was collected from these rats on multiple occasions from Day 29 to Day 71 and samples were analysed for Pig-a mutation using the rat MutaFlow kit. Frequencies of reticulocytes (RET), mutant phenotype erythrocytes (RBC CD59– ) and mutant phenotype RET (RET CD59– ) were determined. Overall, the proportion of RET and frequencies of RBC CD59– and of RET CD59– were consistent throughout the different assessments. The assay demonstrated acceptable intra-run and inter-run variability with coefficients of variation of ≤4.8 and 20.6%, respectively. The method was shown to be independent of the analyst performing the assay and unaffected by small changes in assay conditions. Comparable results were obtained from freshly collected samples and samples refrigerated for up to 4 days. Although technically challenging, the rat Pig-a gene mutation assay using a high-throughput automated method was shown to be reliable. The different assay parameters evaluated during the conduct of this study yielded acceptable results. Thus, the method was considered suitable for use in GLP toxicology studies.

Description: Research over the years has generated enough evidence to implicate areca nut, as a carcinogen in humans. Besides oral, significant rise in the incidence of cancers of the oesophagus, liver and stomach was seen among areca nut chewers. Early diagnosis seems key to understand the initial processes of carcinogenesis which is highly curable. In North-East India, betel quid contains raw areca nut (RAN), lime and small portion of betel leaf without any other constituents. This study was not intended to isolate any active ingredients from the RAN and to look its action. The present objective is to validate the screening of precocious anaphase and analysis of expression of Securin and p53 in non-target cells like human peripheral blood lymphocytes (PBLs) and mouse bone marrow cells (BMCs) as early indicative parameters of RAN + lime-induced cancers. A total of 35 mice were examined at different time points for following ad libitum administration of RAN extract in drinking water with lime. Peripheral blood was collected from 32 human donors of which, 24 were RAN + lime heavy chewers. Expression of genes was assessed by immunoblotting and/or by immunohistochemistry. Histological preparation of stomach tissue of mice revealed that RAN + lime induced stomach cancer. A gradual increase in the frequency of precocious anaphases and aneuploid cells was observed in both RAN + lime-treated mouse BMC and human PBL of RAN heavy chewers. Levels of p53 and Securin were increased in these cells during early days of RAN + lime exposure. The level of Securin was significantly higher in human tumour samples than their adjacent normal counterpart. The expression of Securin was increased significantly in RAN + lime-administered mice as well as in stomach tumour. Present study revealed that precocious anaphase and expression of p53 and Securin in non-target cells are significantly associated with an increased risk of RAN-induced cancer and thus these parameters can be of early diagnostic value.

Description: Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials due to their antibacterial properties. Owing to the recent boost in the usage of AgNPs-containing products, human exposure to AgNPs is increasing, highlighting the need for careful evaluation of AgNPs toxicity in humans. We used two cellular models, hepatic HepG2 and epithelial A549 cell lines, to study the mechanism of AgNPs-induced toxicity at the cellular level. These two cell lines differ significantly in their response to AgNPs treatment. In the case of A549 cells, a minor decrease in viability and increase in the extent of DNA breakage were observed. A markedly different response to AgNPs was observed in HepG2 cells. In short term, a massive induction of DNA breakage was observed, suggesting that the basal activity of antioxidant defence in these cells was not sufficient to effectively protect them from the nanoparticle-induced oxidative stress. After prolonged exposure, the extent of DNA breakage decreased to the level observed in the control cells proving that a successful adaptation to the new conditions had taken place. The cells that were unable to adapt must have died, as revealed by the Neutral Red assay that indicated less than half viable cells after 24-h treatment with 100 µg/ml of 20nm AgNPs. The gene expression analysis revealed that the observed adaptation was underlain by a pro-proliferative, anti-apoptotic signal leading to up-regulation of the genes promoting proliferation and inflammatory response ( EGR1 , FOS , JUN , HK2 , IL4 , MMP10 , VEGFA , WISP1 , CEBPB , IL8 , SELPLG ), genes coding the anti-apoptotic proteins ( BCL2A1 , CCL2 ) and factors involved in the response to stress ( HSPB1 , GADD45A ). Such a selection of highly resistant population of cells should be taken into account in the case of medical applications of nanoparticles since the sustained proliferative signalling and resistance to cell death are hallmarks of cancer, acquired by the cells in the process of carcinogenesis.

Description: Ionising radiation induces single-strand breaks, double-strand breaks (DSB) and base damages in human cell. DSBs are the most deleterious and if not repaired may lead to genomic instability and cell death. DSB can be repaired through non-homologous end joining (NHEJ) pathway in resting lymphocytes. In this study, NHEJ genes and proteins were studied in irradiated human peripheral blood mononuclear cells (PBMC) at resting stage. Dose-response, time point kinetics and adaptive-response studies were conducted in irradiated PBMC at various end points such as DNA damage quantitation, transcription and protein expression profile. Venous blood samples were collected from 20 random, normal and healthy donors with written informed consent. PBMC was separated and irradiated with various doses between 0.1 and 2.0 Gy ( 60 CO- source) for dose-response study. Repair kinetics of DNA damage and time point changes in expression of genes and proteins were studied in post-irradiated PBMC at 2.0 Gy at various time points up to 240min. Adaptive-response study was conducted with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4-h incubation. Our results revealed that Ku70, Ku80, XLF and Ligase IV were significantly upregulated ( P 〈 0.05) at 4-h post-irradiation at transcript and protein level. Adaptive-response study showed significantly increased expression of the proteins involved in NHEJ, suggesting their role in adaptive response in human PBMC at G 0 /G 1, which has important implications to human health.

Description: Excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing groups 1 (XRCC1) are DNA repair enzymes. Polymorphisms in DNA repair genes may be important factors affecting cancer susceptibility, prognosis and therapy outcome. The purpose of this study was to investigate the correlation of ERCC1 and XRCC1 polymorphisms with colorectal cancer (CRC) risk, and explore the effect of polymorphisms on event-free, overall survival and oxaliplatin-based therapy in CRC patients. Genotyping was examined with the iMLDR technique. An unconditional logistic regression model was used to estimate the association of certain polymorphisms with CRC risk. The Kaplan–Meier method, log-rank test and Cox regression model were employed to evaluate the effects of polymorphisms on survival analysis. Results showed that Trp/Trp genotype of XRCC1 Arg194Trp and AA genotype of ERCC1 rs2336219 have a significantly increased risk of CRC; Trp allele of XRCC1 Arg194Trp and CC genotype of ERCC1 rs735482 were associated with lower response to oxaliplatin-based chemotherapy, a shorter survival and a higher risk of relapse or metastasis. 194Trp/280Arg/399Arg haplotype was associated with a significant resistance, and the ERCC1 protein expression was statistically higher in tumours with rs735482 CC genotype than with AA genotype. Our studies indicate that XRCC1 and ERCC1 polymorphisms probably affect susceptibility, chemotherapy response and survival of CRC patients.

Description: Epigenetic control of gene expression in children remains poorly understood, but new technologies can help elucidate the relationship between expression and DNA methylation. Here, we utilized the nCounter Analysis System to characterise the expression of 60 genes in 69 9-year-old children from a cohort with a high prevalence of obesity. nCounter expression levels ranged broadly (from 3 to over 10000 messenger RNA counts) and were divided into four categories: high (〉2000 counts), moderate (200–1000 counts), low (100–200 counts) and marginal (〈100 counts). For a subset of five genes ( ADIPOR1 , PPARG1 , GSTM1 , PON1 and ACACA ) from different expression level categories, we validated nCounter data using reverse transcription-polymerase chain reaction (RT-PCR), and expanded RT-PCR analysis of ADIPOR1 to include 180 children. Expression data from the two methodologies were correlated for all five genes included in the validation experiment, with estimates ranging from r s = 0.26 ( P = 0.02) to r s = 0.88 ( P 〈 5 x 10 –6 ). ADIPOR1 and PPARG1 nCounter expression levels were negatively correlated ( r = –0.60, P 〈 5 x 10 –5 ), and this relationship was stronger in overweight children ( r = –0.73, P 〈 5 x 10 –5 ) than in normal weight children ( r = –0.42, P = 0.016). Using methylation data from the Infinium HumanMethylation450 BeadChip ( n = 180), we found eight CpG sites in ADIPOR1 and PPARG where methylation level was associated with expression by RT-PCR ( P 〈 0.05). Hypomethylation of PPARG gene body site cg10499651 was associated with increased expression as measured by both RT-PCR and nCounter ( P 〈 0.05). We found no statistically significant relationships between either expression or methylation of ADIPOR1 and PPARG and body mass index or waist circumference. In addition to demonstrating the validity of expression data derived from nCounter, our results illustrate the use of new technologies in assessing epigenetic effects on expression in children.

Description: The in vitro micronucleus test is a well-known test for the screening of genotoxic compounds. However until now, most studies have been performed on either human peripheral lymphocytes or established cancer cell lines. This study provides human mesenchymal stem cells as an alternative to the conventional micronucleus test. We grew umbilical cord mesenchymal stem cells (UC-MSCs) on coverslips eliminating the cumbersome technique involving hypotonic treatment, fixation and preparing smears required for suspension culture (lymphocytes). The background frequency of nuclear blebs and micronuclei in UC-MSCs was found to be 7±5, in lymphocytes 16±3.5 and 9±3 and that for A549 cell line was 65±5 and 15±5 per 1000 cells, respectively, suggesting differences in the repair mechanism of normal and cancer cell lines. We inspected the cytotoxic and genotoxic effects of two known mutagens, mitomycin-C and hydrogen peroxide (H 2 O 2 ), on UC-MSCs, lymphocytes and A549 cells. Treatment with mitomycin-C and H 2 O 2 demonstrated drastic differences in the degree of cytotoxicity and genotoxicity suggesting a constitutional difference between normal and cancer cells. In addition we tested two solvents, dimethyl sulfoxide (DMSO) and ethanol, and two drugs, metformin and rapamycin. DMSO above 1% was found to be cytotoxic and genotoxic, whereas ethanol at same concentration was neither cytotoxic nor genotoxic indicating the minimal non-toxic level of the solvents. This study thus offers UC-MSCs as a better substitute to peripheral lymphocytes and cancer cell lines for high throughput screening of compounds and reducing the animal studies.

Description: Cells exhibiting radiation-induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during n ormal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.