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  • Articles  (23,654)
  • Oxford University Press  (23,654)
  • Monthly Notices of the Royal Astronomical Society / Letters  (720)
  • Journal of Biochemistry  (533)
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  • Articles  (23,654)
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  • Oxford University Press  (23,654)
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  • 1
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    CO observations towards H i-rich Ultradiffuse Galaxies (2020)
    Oxford University Press
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    Publication Date: 2020-08-27
    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.
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  • 2
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    Exploring the origin of ultra-diffuse galaxies in clusters from their primordial alignment (2020)
    Oxford University Press
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    Publication Date: 2020-07-16
    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.
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  • 3
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    Silicon ISM X-ray absorption: the gaseous component (2020)
    Oxford University Press
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    Publication Date: 2020-07-11
    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.
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  • 4
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    The origin of the black hole offset in M31 (2020)
    Oxford University Press
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    Publication Date: 2020-07-11
    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.
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  • 5
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    No evidence for interstellar planetesimals trapped in the Solar system (2020)
    Oxford University Press
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    Publication Date: 2020-06-12
    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.
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  • 6
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    The first simultaneous measurement of Hubble constant and post-Newtonian parameter from time-delay strong lensing (2020)
    Oxford University Press
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    Publication Date: 2020-06-18
    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.
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  • 7
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    Have hierarchical three-body mergers been detected by LIGO/Virgo? (2020)
    Oxford University Press
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    Publication Date: 2020-07-10
    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.
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  • 8
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    The stringent upper limit on jet power in the persistent soft-state source 4U 1957+11 (2020)
    Oxford University Press
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    Publication Date: 2020-07-10
    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.
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  • 9
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    Swift J004427.3−734801 – a probable Be/white dwarf system in the Small Magellanic Cloud (2020)
    Oxford University Press
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    Publication Date: 2020-06-12
    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.
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  • 10
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    Detecting isolated stellar-mass black holes in the absence of microlensing parallax effect (2020)
    Oxford University Press
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    Publication Date: 2020-07-10
    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.
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  • 11
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    Erratum: The fifth main-sequence magnetic B-type star showing coherent radio emission: Is this really a rare phenomenon? (2020)
    Oxford University Press
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    Publication Date: 2020-07-04
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  • 12
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    Contrasting copper evolution in   Centauri and the Milky Way (2007)
    Oxford University Press
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    Publication Date: 2007-06-01
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  • 13
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    L and T dwarfs in the Hyades and Ursa Major moving groups (2007)
    Oxford University Press
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    Publication Date: 2007-06-01
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  • 14
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    ALMA imaging of SDP.81 - II. A pixelated reconstruction of the CO emission lines (2015)
    Oxford University Press
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    Publication Date: 2015-08-14
    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.
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  • 15
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    Where are the solar magnetic poles? (2015)
    Oxford University Press
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    Publication Date: 2015-08-24
    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.
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  • 16
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    The offsets between galaxies and their dark matter in {Lambda} cold dark matter (2015)
    Oxford University Press
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    Publication Date: 2015-08-21
    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.
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  • 17
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    Magnetic field rotations in the solar wind at kinetic scales (2015)
    Oxford University Press
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    Publication Date: 2015-08-24
    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.
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  • 18
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    Detection of fundamental and first harmonic cyclotron line in X-ray pulsar Cep X-4 (2015)
    Oxford University Press
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    Publication Date: 2015-08-12
    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.
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  • 19
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    Rotation-induced deep crustal heating of millisecond pulsars (2015)
    Oxford University Press
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    Publication Date: 2015-08-14
    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.
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  • 20
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    Gas-phase formation of the prebiotic molecule formamide: insights from new quantum computations (2015)
    Oxford University Press
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    Publication Date: 2015-08-14
    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.
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  • 21
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    Galactic interstellar filaments as probed by LOFAR and Planck (2015)
    Oxford University Press
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    Publication Date: 2015-09-25
    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.
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  • 22
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    ALMA images of discs: are all gaps carved by planets? (2015)
    Oxford University Press
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    Publication Date: 2015-09-25
    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.
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  • 23
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    Formation of emission line dots and extremely metal-deficient dwarfs from almost dark galaxies (2015)
    Oxford University Press
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    Publication Date: 2015-09-25
    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.
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  • 24
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    Discovery of two new bright magnetic B stars: i Car and Atlas (2015)
    Oxford University Press
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    Publication Date: 2015-09-28
    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.
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  • 25
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    Carbon production on accreting neutron stars in a new regime of stable nuclear burning (2015)
    Oxford University Press
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    Publication Date: 2015-11-23
    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.
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    The disappearance of the progenitor of SN 2012aw in late-time imaging (2015)
    Oxford University Press
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    Publication Date: 2015-11-23
    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.
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    Mutagenesis study to disrupt electrostatic interactions on the twofold symmetry interface of Escherichia coli bacterioferritin (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Ferritins and other cage proteins have been utilized as models to understand the fundamentals of protein folding and self-assembly. The bacterioferritin (BFR) from Escherichia coli, a maxi-ferritin made up of 24 subunits, was chosen as the basis for a mutagenesis study to investigate the role of electrostatic intermolecular interactions mediated through charged amino acids. Through structural and computational analyses, three charged amino acids R30, D56 and E60 which involved in an electrostatic interaction network were mutated to the opposite charge. Four mutants, R30D, D56R, E60H and D56R-E60H, were expressed, purified and characterized. All of the mutants fold into α-helical structures. Consistent with the computational prediction, they all show a lowered thermostability; double mutant D56R-E60H was found to be 16°C less stable than the wild type. Except for the mutant E60H, all the other mutations completely shut down the formation of protein cages to favour the dimer state in solution. The mutants, however, retain their ability to form cage-like nanostructures in the dried, surface immobilized conditions of transmission electron microscopy. Our findings confirm that even a single charge-inversion mutation at the 2-fold interface of BFR can affect the quaternary structure of its dimers and their ability to self-assemble into cage structures.
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    Effect of FliG three amino acids deletion in Vibrio polar-flagellar rotation and formation (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Most of bacteria can swim by rotating flagella bidirectionally. The C ring, located at the bottom of the flagellum and in the cytoplasmic space, consists of FliG, FliM and FliN, and has an important function in flagellar protein secretion, torque generation and rotational switch of the motor. FliG is the most important part of the C ring that interacts directly with a stator subunit. Here, we introduced a three-amino acids in-frame deletion mutation (PSA) into FliG from Vibrio alginolyticus , whose corresponding mutation in Salmonella confers a switch-locked phenotype, and examined its phenotype. We found that this FliG mutant could not produce flagellar filaments in a fliG null strain but the FliG(PSA) protein could localize at the cell pole as does the wild-type protein. Unexpectedly, when this mutant was expressed in a wild-type strain, cells formed flagella efficiently but the motor could not rotate. We propose that this different phenotype in Vibrio and Salmonella might be due to distinct interactions between FliG mutant and FliM in the C ring between the bacterial species.
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    Sulphation of acetaminophen by the human cytosolic sulfotransferases: a systematic analysis (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Sulphation is known to be critically involved in the metabolism of acetaminophen in vivo . This study aimed to systematically identify the major human cytosolic sulfotransferase (SULT) enzyme(s) responsible for the sulphation of acetaminophen. A systematic analysis showed that three of the twelve human SULTs, SULT1A1, SULT1A3 and SULT1C4, displayed the strongest sulphating activity towards acetaminophen. The pH dependence of the sulphation of acetaminophen by each of these three SULTs was examined. Kinetic parameters of these three SULTs in catalysing acetaminophen sulphation were determined. Moreover, sulphation of acetaminophen was shown to occur in HepG2 human hepatoma cells and Caco-2 human intestinal epithelial cells under the metabolic setting. Of the four human organ samples tested, liver and intestine cytosols displayed considerably higher acetaminophen-sulphating activity than those of lung and kidney. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of acetaminophen in vivo previously reported.
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    Expression, purification and enzymatic characterization of a recombinant human ubiquitin-specific protease 47 (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: In this study, the physicochemical and enzymatic properties of recombinant human ubiquitin (Ub)-specific protease (USP) 47, a novel member of the C19 family of de-ubiquitinating enzymes (DUB), were characterized for the first time. Recombinant human USP47 was expressed in a baculovirus expression system and purified to homogeneity. The purified protein was shown to be a monomeric protein with a molecular mass of ~146 kDa on sodium dodecyl sulphate—polyacrylamide gel electrophoresis. USP47 released Ub from Ub-aminoacyl-4-metheylcoumaryl-7-amide and Ub-tagged granzyme B. The substitution of the potential nucleophile Cys109 with Ser severely abrogated the Ub-releasing activity of USP47, indicating that USP47 is indeed a cysteine DUB. An assay using Ub dimer substrates showed that the enzyme cleaved a variety of isopeptide bonds between 2 Ub molecules, including the Lys48- and Lys63-linked isopeptide bonds. USP47 also released a Ub moiety from Lys48- and Lys63-linked polyUb chains. Of the inhibitors tested, N -ethylmaleimide, Zn ion and Ub aldehyde revealed a dose-dependent inhibition of USP47. In this study, clear differences in the enzymatic properties between USP47 and USP7 (the most closely related proteins among DUBs) were also found. Therefore, our results suggest that USP47 may play distinct roles in Ub-mediated cellular processes via DUB activity.
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    In vitro affinity maturation and characterization of anti-P24 antibody for HIV diagnostic assay (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: P24 antigen is the main structural protein of HIV-1, its detection provide a means to aid the early diagnosis of HIV-1 infection. The aim of this study was to improve the selectivity and sensitivity of the HIV P24 diagnostic assay by developing a cohort of 9E8 affinity-matured antibodies through in vitro phage affinity maturation which was performed by complementarity determining region (CDR)-hot spot mutagenesis strategy. Antibody 9E8-491 had an affinity constant of 5.64 x 10 –11 M, which was 5.7-fold higher than that of the parent antibody (9E8). Furthermore, the affinity, sensitivity and specificity of 9E8-491 were higher than those of 9E8, which indicate that 9E8-491 is a good candidate detection antibody for HIV P24 assay. Structure analysis of matured variants revealed that most hydrogen bonds resided in HCDR3. Among the antibody–antigen predicted binding residues, Tyr 100A/100B was the original conserved residue that was commonly present in HCDR3 of 9E8 and variants. Arg 100 /Asp 100C was the major variant substitution that most likely influenced the binding differences among variants and 9E8 monoclonal antibody. Both efficient library panning and predicted structural data were in agreement that the binding residues were mostly located in HCDR3 and enabled identification of key residues that influence antibody affinity.
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    CO luminosity function from Herschel-selected galaxies and the contribution of AGN (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    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.
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    On the use of the number count of blue horizontal branch stars to infer the dominant building blocks of the Milky Way halo (2015)
    Oxford University Press
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    Publication Date: 2015-11-23
    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.
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    Dynamic and distinct histone modifications of osteogenic genes during osteogenic differentiation (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Many skeletal diseases have common pathological phenotype of defective osteogenesis of bone marrow stromal cells (BMSCs), in which histone modifications play an important role. However, few studies have examined the dynamics of distinct histone modifications during osteogenesis. In this study, we examined the dynamics of H3K9/K14 and H4K12 acetylation; H3K4 mono-, di- and tri-methylation; H3K9 di-methylation and H3K27 tri-methylation in osteogenic genes, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase, bone sialoprotein and osteocalcin, during C3H10T1/2 osteogenesis. H3 and H4 acetylation and H3K4 di-methylation were elevated, and H3K9 di-methylation and H3K27 tri-methylation were reduced in osteogenic genes during C3H10T1/2 osteogenesis. C3H10T1/2 osteogenesis could be modulated by altering the patterns of H3 and H4 acetylation and H3K27 tri-methylation. In a glucocorticoid-induced osteoporosis mouse model, we observed the attenuation of osteogenic potential of osteoporotic BMSCs in parallel with H3 and H4 hypo-acetylation and H3K27 hyper-tri-methylation in Runx2 and Osx genes. When H3 and H4 acetylation was elevated, and H3K27 tri-methylation was reduced, the attenuated osteogenic potential of osteoporotic BMSCs was rescued effectively. These observations provide a deeper insight into the mechanisms of osteogenic differentiation and the pathophysiology of osteoporosis and can be used to design new drugs and develop new therapeutic methods to treat skeletal diseases.
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    In vitro dihydrouridine formation by tRNA dihydrouridine synthase from Thermus thermophilus, an extreme-thermophilic eubacterium (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Dihydrouridine (D) is formed by tRNA dihydrouridine synthases (Dus). In mesophiles, multiple Dus enzymes bring about D modifications at several positions in tRNA. The extreme-thermophilic eubacterium Thermus thermophilus , in contrast, has only one dus gene in its genome and only two D modifications (D20 and D20a) in tRNA have been identified. Until now, an in vitro assay system for eubacterial Dus has not been reported. In this study, therefore, we constructed an in vitro assay system using purified Dus. Recombinant T. thermophilus Dus lacking bound tRNA was successfully purified. The in vitro assay revealed that no other factors in living cells were required for D formation. A dus gene disruptant ( dus ) strain of T. thermophilus verified that the two D20 and D20a modifications in tRNA were derived from one Dus protein. The dus strain did not show growth retardation at any temperature. The assay system showed that Dus modified tRNA Phe transcript at 60°C, demonstrating that other modifications in tRNA are not essential for Dus activity. However, a comparison of the formation of D in native tRNA Phe purified from the dus strain and tRNA Phe transcript revealed that other tRNA modifications are required for D formation at high temperatures.
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    Yeast cell-based analysis of human lactate dehydrogenase isoforms (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Human lactate dehydrogenase (LDH) has attracted attention as a potential target for cancer therapy and contraception. In this study, we reconstituted human lactic acid fermentation in Saccharomyces cerevisiae , with the goal of constructing a yeast cell-based LDH assay system. pdc null mutant yeast (mutated in the endogenous pyruvate decarboxylase genes) are unable to perform alcoholic fermentation; when grown in the presence of an electron transport chain inhibitor, pdc null strains exhibit a growth defect. We found that introduction of the human gene encoding LDHA complemented the pdc growth defect; this complementation depended on LDHA catalytic activity. Similarly, introduction of the human LDHC complemented the pdc growth defect, even though LDHC did not generate lactate at the levels seen with LDHA. In contrast, the human LDHB did not complement the yeast pdc null mutant, although LDHB did generate lactate in yeast cells. Expression of LDHB as a red fluorescent protein (RFP) fusion yielded blebs in yeast, whereas LDHA-RFP and LDHC-RFP fusion proteins exhibited cytosolic distribution. Thus, LDHB exhibits several unique features when expressed in yeast cells. Because yeast cells are amenable to genetic analysis and cell-based high-throughput screening, our pdc /LDH strains are expected to be of use for versatile analyses of human LDH.
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    Visualization of RelB expression and activation at the single-cell level during dendritic cell maturation in Relb-Venus knock-in mice (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: RelB is activated by the non-canonical NF-B pathway, which is crucial for immunity by establishing lymphoid organogenesis and B-cell and dendritic cell (DC) maturation. To elucidate the mechanism of the RelB-mediated immune cell maturation, a precise understanding of the relationship between cell maturation and RelB expression and activation at the single-cell level is required. Therefore, we generated knock-in mice expressing a fusion protein between RelB and fluorescent protein (RelB-Venus) from the Relb locus. The Relb Venus / Venus mice developed without any abnormalities observed in the Relb –/– mice, allowing us to monitor RelB-Venus expression and nuclear localization as RelB expression and activation. Relb Venus / Venus DC analyses revealed that DCs consist of RelB – , RelB low and RelB high populations. The RelB high population, which included mature DCs with projections, displayed RelB nuclear localization, whereas RelB in the RelB low population was in the cytoplasm. Although both the RelB low and RelB – populations barely showed projections, MHC II and co-stimulatory molecule expression were higher in the RelB low than in the RelB – splenic conventional DCs. Taken together, our results identify the RelB low population as a possible novel intermediate maturation stage of cDCs and the Relb Venus / Venus mice as a useful tool to analyse the dynamic regulation of the non-canonical NF-B pathway.
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    Molecular and biochemical characterization of bifunctional pyruvate decarboxylases and pyruvate ferredoxin oxidoreductases from Thermotoga maritima and Thermotoga hypogea (2015)
    Oxford University Press
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    Publication Date: 2015-11-26
    Description: Hyperthermophilic bacteria Thermotoga maritima and Thermotoga hypogea produce ethanol as a metabolic end product, which is resulted from acetaldehyde reduction catalysed by an alcohol dehydrogenase (ADH). However, the enzyme that is involved in the production of acetaldehyde from pyruvate is not well characterized. An oxygen sensitive and coenzyme A-dependent pyruvate decarboxylase (PDC) activity was found to be present in cell free extracts of T. maritima and T. hypogea . Both enzymes were purified and found to have pyruvate ferredoxin oxidoreductase (POR) activity, indicating their bifunctionality. Both PDC and POR activities from each of the purified enzymes were characterized in regards to their optimal assay conditions including pH dependency, oxygen sensitivity, thermal stability, temperature dependency and kinetic parameters. The close relatedness of the PORs that was shown by sequence analysis could be an indication of the presence of such bifunctionality in other hyperthermophilic bacteria. This is the first report of a bifunctional PDC/POR enzyme in hyperthermophilic bacteria. The PDC and the previously reported ADHs are most likely the key enzymes catalysing the production of ethanol from pyruvate in bacterial hyperthermophiles.
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    Simulating feedback from nuclear clusters: the impact of multiple sources (2015)
    Oxford University Press
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    Publication Date: 2015-11-25
    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.
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    On planet formation in HL Tau (2015)
    Oxford University Press
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    Publication Date: 2015-08-27
    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.
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    ALMA and Herschel reveal that X-ray-selected AGN and main-sequence galaxies have different star formation rate distributions (2015)
    Oxford University Press
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    Publication Date: 2015-08-27
    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.
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    Magnetar activity via the density-shear instability in Hall-MHD (2015)
    Oxford University Press
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    Publication Date: 2015-08-29
    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.
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    Low pH-driven folding of WW45-SARAH domain leads to stabilization of the WW45-Mst2 complex (2015)
    Oxford University Press
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    Publication Date: 2015-08-30
    Description: The scaffolding protein Salvador (Sav) plays a key role in the Hippo (Hpo) signalling pathway, which controls tissue growth by inhibiting cell proliferation and promoting apoptosis. Dysregulation of the Hippo pathway contributes to cancer development. Since the identification of the first Sav gene in 2002, very little is known regarding the molecular basis of Sav-SARAH mediating interactions due to its insolubility. In this study, refolding of the first Sav (known as WW45)-SARAH provided insight into the biochemical and biophysical properties, indicating that WW45-SARAH exhibits properties of a disordered protein, when the domain was refolded at a neutral pH. Interestingly, WW45-SARAH shows folded and rigid conformations relative to the decrease in pH. Further, diffracting crystals were obtained from protein refolded under acidic pH, suggesting that the refolded WW45 protein at low pH has a homogeneous and stable conformation. A comparative analysis of molecular properties found that the acidic-stable fold of WW45-SARAH enhances a heterotypic interaction with Mst2-SARAH. In addition, using an Mst2 mutation that disrupts homotypic dimerization, we showed that the monomeric Mst2-SARAH domain could form a stable complex of 1:1 stoichiometric ratio with WW45 refolded under acidic pH.
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    Diet-induced hypercholesterolemia imparts structure-function changes to erythrocyte chondroitin sulphate/dermatan sulphate (2015)
    Oxford University Press
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    Publication Date: 2015-08-30
    Description: Hypercholesterolemia is one of the factors contributing to cardiovascular problems. Erythrocytes are known to contribute its cholesterol to atherosclerotic plaque. Our earlier study showed that erythrocytes overexpress chondroitin sulphate/dermatan sulphate (CS/DS), a linear co-polymer, during diabetes which resulted in increased cytoadherence to extracellular matrix (ECM) components. This study was carried out to determine whether diet-induced hypercholesterolemia had any effect on erythrocyte CS/DS and impacted cytoadherence to ECM components. Unlike in diabetes, diet-induced hypercholesterolemia did not show quantitative changes in erythrocyte CS/DS but showed difference in proportion of un-sulphated and 4- O -sulphated disaccharides. Erythrocytes from hypercholesterolemic rats showed increased adhesion to ECM components which was abrogated to various extents when subjected to chondroitinase ABC digestion. However, isolated CS/DS chains showed a different pattern of binding to ECM components indicating that orientation of CS/DS chains could be playing a role in binding.
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    Isolation and characterization of antigen-specific alpaca (Lama pacos) VHH antibodies by biopanning followed by high-throughput sequencing (2015)
    Oxford University Press
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    Publication Date: 2015-08-30
    Description: The antigen-binding domain of camelid dimeric heavy chain antibodies, known as VHH or Nanobody, has much potential in pharmaceutical and industrial applications. To establish the isolation process of antigen-specific VHH, a VHH phage library was constructed with a diversity of 8.4 x 10 7 from cDNA of peripheral blood mononuclear cells of an alpaca ( Lama pacos ) immunized with a fragment of IZUMO1 (IZUMO1 PFF ) as a model antigen. By conventional biopanning, 13 antigen-specific VHHs were isolated. The amino acid sequences of these VHHs, designated as N-group VHHs, were very similar to each other (〉93% identity). To find more diverse antibodies, we performed high-throughput sequencing (HTS) of VHH genes. By comparing the frequencies of each sequence between before and after biopanning, we found the sequences whose frequencies were increased by biopanning. The top 100 sequences of them were supplied for phylogenic tree analysis. In total 75% of them belonged to N-group VHHs, but the other were phylogenically apart from N-group VHHs (Non N-group). Two of three VHHs selected from non N-group VHHs showed sufficient antigen binding ability. These results suggested that biopanning followed by HTS provided a useful method for finding minor and diverse antigen-specific clones that could not be identified by conventional biopanning.
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    The R3 receptor-like protein tyrosine phosphatase subfamily inhibits insulin signalling by dephosphorylating the insulin receptor at specific sites (2015)
    Oxford University Press
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    Publication Date: 2015-08-30
    Description: The autophosphorylation of specific tyrosine residues occurs in the cytoplasmic region of the insulin receptor (IR) upon insulin binding, and this in turn initiates signal transduction. The R3 subfamily (Ptprb, Ptprh, Ptprj and Ptpro) of receptor-like protein tyrosine phosphatases (RPTPs) is characterized by an extracellular region with 6–17 fibronectin type III-like repeats and a cytoplasmic region with a single phosphatase domain. We herein identified the IR as a substrate for R3 RPTPs by using the substrate-trapping mutants of R3 RPTPs. The co-expression of R3 RPTPs with the IR in HEK293T cells suppressed insulin-induced tyrosine phosphorylation of the IR. In vitro assays using synthetic phosphopeptides revealed that R3 RPTPs preferentially dephosphorylated a particular phosphorylation site of the IR: Y960 in the juxtamembrane region and Y1146 in the activation loop. Among four R3 members, only Ptprj was co-expressed with the IR in major insulin target tissues, such as the skeletal muscle, liver and adipose tissue. Importantly, the activation of IR and Akt by insulin was enhanced, and glucose and insulin tolerance was improved in Ptprj -deficient mice. These results demonstrated Ptprj as a physiological enzyme that attenuates insulin signalling in vivo , and indicate that an inhibitor of Ptprj may be an insulin-sensitizing agent.
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    Involvement of thioredoxin on the scaffold activity of NifU in heterocyst cells of the diazotrophic cyanobacterium Anabaena sp. strain PCC 7120 (2015)
    Oxford University Press
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    Publication Date: 2015-08-30
    Description: The diazotrophic cyanobacterium Anabaena sp. strain PCC 7120 (A.7120) differentiates into specialized heterocyst cells that fix nitrogen under nitrogen starvation conditions. Although reducing equivalents are essential for nitrogen fixation, little is known about redox systems in heterocyst cells. In this study, we investigated thioredoxin (Trx) networks in Anabaena using TrxM, and identified 16 and 38 candidate target proteins in heterocysts and vegetative cells, respectively, by Trx affinity chromatography (Motohashi et al. (Comprehensive survey of proteins targeted by chloroplast thioredoxin. Proc Natl Acad Sci USA , 2001; 98 , 11224–11229)). Among these, the Fe–S cluster scaffold protein NifU that facilitates functional expression of nitrogenase in heterocysts was found to be a potential TrxM target. Subsequently, we observed that the scaffold activity of N-terminal catalytic domain of NifU is enhanced in the presence of Trx-system, suggesting that TrxM is involved in the Fe–S cluster biogenesis.
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    {gamma}-ray emission states in the redback millisecond pulsar binary system PSR J1227-4853 (2015)
    Oxford University Press
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    Publication Date: 2015-05-31
    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.
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    Substrate-dependent nitric oxide synthesis by secreted endoplasmic reticulum aminopeptidase 1 in macrophages (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: In this study, we examined the role of aminopeptidases with reference to endoplasmic reticulum aminopeptidase 1 (ERAP1) in nitric oxide (NO) synthesis employing murine macrophage cell line RAW264.7 cells activated by lipopolysaccharide (LPS) and interferon (IFN)- and LPS-activated peritoneal macrophages derived from ERAP1 knockout mouse. When NO synthesis was measured in the presence of peptides having N-terminal Arg, comparative NO synthesis was seen with that measured in the presence of Arg. In the presence of an aminopeptidase inhibitor amastatin, NO synthesis in activated RAW264.7 cells was significantly decreased. These results suggest that aminopeptidases are involved in the NO synthesis in activated RAW264.7 cells. Subsequently, significant reduction of NO synthesis was observed in ERAP1 knockdown cells compared with wild-type cells. This reduction was rescued by exogenously added ERAP1. Furthermore, when peritoneal macrophages prepared from ERAP1 knockout mouse were employed, reduction of NO synthesis in knockout mouse macrophages was also attributable to ERAP1. In the presence of amastatin, further reduction was observed in knockout mouse-derived macrophages. Taken together, these results suggest that several aminopeptidases play important roles in the maximum synthesis of NO in activated macrophages in a substrate peptide-dependent manner and ERAP1 is one of the aminopeptidases involved in the NO synthesis.
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    Properties and functions of the storage sites of glycogen phosphorylase (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits. Each subunit has two distinct maltooligosaccharide binding sites: a storage site and a catalytic site. Our characterization of the properties of these sites suggested that GP activity consists of two activities: (i) binding to the glycogen molecule and (ii) phosphorolysis of the non-reducing-end glucose residues. Activity (i) is mainly due to the activities of the two storage sites, which depended on the ionic strength of the medium and were directly inhibited by cyclodextrins (CDs). Activity (i) is of benefit to GP because a high concentration of non-reducing-end glucose residues is localized on the surface of the glycogen molecule. Activity (ii), the total activity of the two catalytic sites, exhibited relatively little ionic strength dependence. Because the combined activity of (i) and (ii) is deduced using glycogen as an assay substrate, the sole activity of (ii) must be measured using small maltooligosyl-substrates. By using a very low concentration of pyridylaminated maltohexaose, we demonstrated that the GP catalytic sites are active even in the presence of CDs, and that the actions of the catalytic site and the storage site are independent of each other.
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    A highly effective and adjustable dual plasmid system for O-GlcNAcylated recombinant protein production in E. coli (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: O -GlcNAcylation is a ubiquitous, dynamic and reversible post-translational protein modification in metazoans, and it is catalysed and removed by O -GlcNAc transferase (OGT) and O -GlcNAcase, respectively. Prokaryotes lack endogenous OGT activity. It has been reported that coexpression of mammalian OGT with its target substrates in Escherichia coli produce O -GlcNAcylated recombinant proteins, but the plasmids used were not compatible, and the expression of both OGT and its target protein were induced by the same inducer. Here, we describe a compatible dual plasmid system for coexpression of OGT and its target substrate for O -GlcNAcylated protein production in E. coli . The approach was validated using the CKII and p53 protein as control. This compatible dual plasmid system contains an arabinose-inducible OGT expression vector with a pUC origin and an isopropyl β - d -thiogalactopyranoside-inducible OGT target substrate expression vector bearing a p15A origin. The dual plasmid system produces recombinant proteins with varying O -GlcNAcylation levels by altering the inducer concentration. More importantly, the O -GlcNAcylation efficiency was much higher than the previously reported system. Altogether, we established an adjustable compatible dual plasmid system that can effectively yield O -GlcNAcylated proteins in E. coli .
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    New roles of DNA and SopB in polymerization of SopA of Escherichia coli F plasmid (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: Active equi-paritioning of the F plasmid is achieved by its sopABC gene. SopA binds to the sopAB promoter region and SopB binds to sopC . SopA also polymerizes in the presence of ATP and Mg(II), which is stimulated by SopB. Non-specific DNA is known to inhibit SopA polymerization and disassemble SopA polymer. This study followed kinetics of polymerization and de-polymerization of SopA by turbidity measurement and found new effects by DNA and SopB. Plasmid DNA, at low concentrations, shortened the lag (nucleation) phase of SopA polymerization and also caused an initial ‘burst’ of turbidity. Results with two non-specific 20-bp DNAs indicated sequence/length dependence of these effects. sopAB operator DNA only showed inhibition of SopA polymerization. Results of turbidity decrease of pre-formed SopA polymer in the presence of ethylenediaminetetraacetic acid showed that SopB also accelerates disassembly of the SopA polymer. The steady-state level of turbidity in the presence of SopB and plasmid DNA indicated synergy between SopB and DNA in the disassembly. SopB protein showed no effect on SopA polymerization, when SopB was specifically bound to DNA. This result and others with truncation mutants of SopB suggested that a proper configuration of the domains of SopB is important for SopA-SopB interactions.
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    Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: Influenza A virus (IAV) has been raising public health and safety concerns worldwide. Cyanovirin-N (CVN) is a prominent anti-IAV candidate, but both cytotoxicity and immunogenicity have hindered the development of this protein as a viable therapy. In this article, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli at a 〉15-l scale. PEGylation at the N-terminal α-amine of LCVN was also reformed as 20 kDa PEGylated linkered Cyanovirin-N (PEG 20k –LCVN). The 50% effective concentrations of PEG 20k –LCVN were 0.43 ± 0.11 µM for influenza A/HK/8/68 (H3N2) and 0.04 ± 0.02 µM for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88 ± 0.66 x 10 3 µM and 1.79 ± 0.62 x 10 3 µM, respectively). A total of 12.5 µM PEG 20k –LCVN effectively inactivate the propagation of H3N2 in chicken embryos. About 2.0 mg/kg/day PEG 20k –LCVN increased double the survival rate (66.67%, P = 0.0378) of H3N2 infected mice, prolonged the median survival period, downregulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG 20k –LCVN, exhibited potent and strain-dependent anti-IAV activity in nanomolar concentrations in vitro, as well as in micromolar concentration in vivo .
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    Overproduction and easy recovery of biofuels from engineered cyanobacteria, autolyzing multicellular cells (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: The semi-filamentous multicellular cyanobacterium Limnothrix / Pseudanabaena sp. strain ABRG5-3 undergoes autolysis, which involves the accumulation of polyphosphate compounds and disintegration of thylakoid membranes in cells, as a unique feature that occurs due to growth conditions. In this study, the overexpression and easy recovery of alkane (a saturated hydrocarbon, C 17 H 36 ) as a biofuel were examined in recombinants of the cyanobacteria ABRG5-3 and Synechocystis sp. strain PCC6803. The results obtained indicated that the accumulated mass of alkane accounted for ~50 or 60% of the dry weight of ABRG5-3 or PCC6803 recombinant cells, respectively. Furthermore, cultivating cells in liquid medium BG11 in which the nitrogen resource had been depleted promoted the production of alkane and cell lysis, resulting in the easy recovery of target products from the supernatant.
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    An early endosome regulator, Rab5b, is an LRRK2 kinase substrate (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: Leucine-rich repeat kinase 2 (LRRK2) has been identified as a causative gene for Parkinson’s disease (PD). LRRK2 contains a kinase and a GTPase domain, both of which provide critical intracellular signal-transduction functions. We showed previously that Rab5b, a small GTPase protein that regulates the motility and fusion of early endosomes, interacts with LRRK2 and co-regulates synaptic vesicle endocytosis. Using recombinant proteins, we show here that LRRK2 phosphorylates Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was confirmed by western analysis using cells stably expressing LRRK2 G2019S. The phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited GTPase activity stronger than that of the unphosphorylated Rab5b protein. Two assays testing Rab5’s activity, neurite outgrowth analysis and epidermal growth factor receptor degradation assays, showed that Rab5b T6D exhibited phenotypes that were expected to be observed in the inactive Rab5b, including longer neurite length and less degradation of EGFR. These results suggest that LRRK2 kinase activity functions as a Rab5b GTPase activating protein and thus, negatively regulates Rab5b signalling.
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    MicroRNAs as the fine-tuners of Src oncogenic signalling (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: The cellular Src (c-Src) tyrosine kinase is upregulated and believed to play a pivotal role in various human cancers. However, the molecular mechanism underlying c-Src-mediated tumour progression remains elusive. Recent studies have revealed that several microRNAs (miRNAs) function as tumour suppressors by regulating the malignant expression of signalling molecules. Aberrant expression of miRNAs is frequently observed in human cancers and should be exploited to seek related molecular targets. In this review, we focus on miRNAs found to be involved in Src signalling in various cancers. We summarize recent findings on Src-related miRNAs, their target genes, mechanisms behind their interplay and their implications for cancer therapeutics.
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    The emerging role of calcium-modulating cyclophilin ligand in posttranslational insertion of tail-anchored proteins into the endoplasmic reticulum membrane (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: Tail-anchored (TA) proteins, a class of membrane proteins having an N-terminal cytoplasmic region anchored to the membrane by a single C-terminal transmembrane domain, are posttranslationally inserted into the endoplasmic reticulum (ER) membrane. In yeasts, the posttranslational membrane insertion is mediated by the Guided Entry of TA Proteins (GET) complex. Get3, a cytosolic ATPase, targets newly synthesized TA proteins to the ER membrane, where Get2 and Get3 constitute the Get3 receptor driving the membrane insertion. While mammalian cells employ TRC40 and WRB, mammalian homologs of Get3 and Get1, respectively, they lack the gene homologous to Get2. We recently identified calcium-modulating cyclophilin ligand (CAML) as a TRC40 receptor, indicating that CAML was equivalent to Get2 in the context of the membrane insertion. On the other hand, CAML has been well characterized as a signaling molecule that regulates various biological processes, raising the question of how the two distinct actions of CAML, the membrane insertion and the signal transduction, are assembled. In this review, we summarize recent progress of the molecular mechanism of the membrane insertion of TA proteins and discuss the possibility that CAML could sense the various signals at the ER membrane, thereby controlling TA protein biogenesis.
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    Basic and aromatic residues in the C-terminal domain of PriC are involved in ssDNA and SSB binding (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: In bacterial organisms, the oriC -independent primosome plays an essential role in replication restart after dissociation of the replication DNA-protein complex following DNA damage. PriC is a key protein component in the oriC -independent replication restart primosome. Our previous study suggested that PriC was divided into an N-terminal domain and a C-terminal domain, with the latter domain being the major contributor to single-stranded DNA (ssDNA) binding capacity. In this study, we prepared several PriC mutants in which basic and aromatic amino acid residues were mutated to alanine. Five of these residues, Arg107, Lys111, Phe118, Arg121 and Lys165 in the C-terminal domain, were shown to be involved in ssDNA binding. Moreover, we evaluated the binding of the PriC mutants to the ssDNA-binding protein (SSB) complex. Five residues, Phe118, Arg121, Arg129, Tyr152 and Arg155 in the C-terminal domain of PriC, were shown to be involved in SSB binding in the presence of ssDNA. On the basis of these results, we propose a structural model of the C-terminal domain of PriC and discuss how the interactions of PriC with SSB and ssDNA may contribute to the regulation of PriC-dependent replication restart.
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    Recombinant expression, molecular characterization and crystal structure of antitumor enzyme, L-lysine {alpha}-oxidase from Trichoderma viride (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: L -Lysine α-oxidase (LysOX) from Trichoderma viride is a homodimeric 112 kDa flavoenzyme that catalyzes the oxidative deamination of L -lysine to form α-keto--aminocaproate. LysOX severely inhibited growth of cancer cells but showed relatively low cytotoxicity for normal cells. We have determined the cDNA nucleotide sequence encoding LysOX from T. viride. The full-length cDNA consists of 2,119 bp and encodes a possible signal peptide (Met1-Arg77) and the mature protein (Ala78-Ile617). The LysOX gene have been cloned and heterologously expressed in Streptomyces lividans TK24 with the enzyme activity up to 9.8 U/ml. The enzymatic properties of the purified recombinant LysOX, such as substrate specificity and thermal stability, are same as those of native LysOX. The crystal structure of LysOX at 1.9 Å resolution revealed that the overall structure is similar to that of snake venom L -amino acid oxidase (LAAO), and the residues involved in the interaction with the amino or carboxy group of the substrate are structurally conserved. However, the entrance and the inner surface structures of the funnel to the active site, as well as the residues involved in the substrate side-chain recognition, are distinct from LAAOs. These structural differences well explain the unique substrate specificity of LysOX.
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    Structure-based design of a streptavidin mutant specific for an artificial biotin analogue (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: For a multistep pre-targeting method using antibodies, a streptavidin mutant with low immunogenicity, termed low immunogenic streptavidin mutant No. 314 (LISA-314), was produced previously as a drug delivery tool. However, endogenous biotins (BTNs) with high affinity ( K d 〈 10 –10 M) for the binding pocket of LISA-314 prevents access of exogenous BTN-labelled anticancer drugs. In this study, we improve the binding pocket of LISA-314 to abolish its affinity for endogenous BTN species, therefore ensuring that the newly designed LISA-314 binds only artificial BTN analogue. The replacement of three amino acid residues was performed in two steps to develop a mutant termed V212, which selectively binds to 6-(5-((3a S ,4 S ,6a R )-2-iminohexahydro-1 H -thieno[3,4- d ]imidazol-4-yl)pentanamido)hexanoic acid (iminobiotin long tail, IMNtail). Surface plasmon resonance results showed that V212 has a K d value of 5.9 x 10 –7 M towards IMNtail, but no binding affinity for endogenous BTN species. This V212/IMNtail system will be useful as a novel delivery tool for anticancer therapy.
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    G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex (2015)
    Oxford University Press
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    Publication Date: 2015-05-28
    Description: A number of gene mutations are detected in cells derived from human cancer tissues, but roles of these mutations in cancer cell development are largely unknown. We examined G364R mutation of MCM4 detected in human skin cancer cells. Formation of MCM4/6/7 complex is not affected by the mutation. Consistent with this notion, the binding to MCM6 is comparable between the mutant MCM4 and wild-type MCM4. Nuclear localization of this mutant MCM4 expressed in HeLa cells supports this conclusion. Purified MCM4/6/7 complex containing the G364R MCM4 exhibited similar levels of single-stranded DNA binding and ATPase activities to the complex containing wild-type MCM4. However, the mutant complex showed only 30–50% of DNA helicase activity of the wild-type complex. When G364R MCM4 was expressed in HeLa cells, it was fractionated into nuclease-sensitive chromatin fraction, similar to wild-type MCM4. These results suggest that this mutation does not affect assembly of MCM2-7 complex on replication origins but it interferes some step at function of MCM2-7 helicase. Thus, this mutation may contribute to cancer cell development by disturbing DNA replication.
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    Hot and dense water in the inner 25 au of SVS13-A (2016)
    Oxford University Press
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    Publication Date: 2016-07-22
    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.
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    Evidence for quasi-periodic oscillations in the optical polarization of the blazar PKS 2155-304 (2016)
    Oxford University Press
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    Publication Date: 2016-07-22
    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.
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    On the radial distribution of Galactic cosmic rays (2016)
    Oxford University Press
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    Publication Date: 2016-08-04
    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.
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    QPO frequency derivative-frequency correlation indicates non-Keplerian boundary layer with a maximum in rotation rate (2016)
    Oxford University Press
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    Publication Date: 2016-08-04
    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.
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    V346 Normae: first post-outburst observations of an FU Orionis star (2016)
    Oxford University Press
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    Publication Date: 2016-07-17
    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.
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    White dwarf pollution by planets in stellar binaries (2016)
    Oxford University Press
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    Publication Date: 2016-07-24
    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.
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    Importin {alpha}: a key molecule in nuclear transport and non-transport functions (2016)
    Oxford University Press
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    Publication Date: 2016-07-30
    Description: Importin α performs the indispensable role of ferrying proteins from the cytoplasm into the nucleus with a transport carrier, importin β1. Mammalian cells from mouse or human contain either six or seven importin α subtypes, respectively, each with a tightly regulated expression. Therefore, the combination of subtype expression in a cell defines distinct signaling pathways to achieve progressive changes in gene expression essential for cellular events, such as differentiation. Recent studies reveal that, in addition to nucleocytoplasmic transport, importin αs also serve non-transport functions. In this review, we first discuss the physiological significance of importin α as a nuclear transport regulator, and then focus on the functional diversities of importin αs based on their specific subcellular and cellular localizations, such as the nucleus and plasma membrane. These findings enrich our knowledge of how importin αs actively contribute to various cellular events.
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    Topics: Biology , Chemistry and Pharmacology
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    Structural and mutational studies of an electron transfer complex of maize sulfite reductase and ferredoxin (2016)
    Oxford University Press
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    Publication Date: 2016-07-30
    Description: The structure of the complex of maize sulfite reductase (SiR) and ferredoxin (Fd) has been determined by X-ray crystallography. Co-crystals of the two proteins prepared under different conditions were subjected to the diffraction analysis and three possible structures of the complex were solved. Although topological relationship of SiR and Fd varied in each of the structures, two characteristics common to all structures were found in the pattern of protein-protein interactions and positional arrangements of redox centres; (i) a few negative residues of Fd contact with a narrow area of SiR with positive electrostatic surface potential and (ii) [2Fe-2S] cluster of Fd and [4Fe-4S] cluster of SiR are in a close proximity with the shortest distance around 12 Å. Mutational analysis of a total of seven basic residues of SiR distributed widely at the interface of the complex showed their importance for supporting an efficient Fd-dependent activity and a strong physical binding to Fd. These combined results suggest that the productive electron transfer complex of SiR and Fd could be formed through multiple processes of the electrostatic intermolecular interaction and this implication is discussed in terms of the multi-functionality of Fd in various redox metabolisms.
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    Fine structures at pore boundary (2016)
    Oxford University Press
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    Publication Date: 2016-08-06
    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.
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    Radio SNRs in the Magellanic Clouds as probes of shock microphysics (2016)
    Oxford University Press
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    Publication Date: 2016-07-07
    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.
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    Water, methanol and dense gas tracers in the local ULIRG Arp 220: results from the new SEPIA Band 5 Science Verification campaign (2016)
    Oxford University Press
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    Publication Date: 2016-07-08
    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.
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    Cosmological N-body simulations with suppressed variance (2016)
    Oxford University Press
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    Publication Date: 2016-07-08
    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.
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    Suppression of mitochondrial transcription initiation complexes changes the balance of replication intermediates of mitochondrial DNA and reduces 7S DNA in cultured human cells (2016)
    Oxford University Press
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    Publication Date: 2016-06-25
    Description: Analysis of replicating mammalian mitochondrial DNA (mtDNA) suggested that initiation of the replication occurs not only at the specific position, Ori-H but also across a broad zone in mtDNA. We investigated relationship of mitochondrial transcription initiation which takes place upstream of Ori-H and mtDNA replication initiation through analysing the effect of knockdown of mitochondrial transcription factor B2, TFB2M and mitochondrial RNA polymerase, POLRMT, components of the transcription initiation complexes in cultured human cells. Under the conditions where suppression of the transcription initiation complexes was achieved by simultaneous depletion of TFB2M and POLRMT, decrease of replication intermediates of mtDNA RITOLS replication mode accompanied reduction in mtDNA copy number. On the other hand, replication intermediates of coupled leading and lagging strand DNA replication, another proposed replication mode, appeared to be less affected. The findings support the view that the former mode involves transcription from the light strand promoter (LSP), and suggest that initiation of the latter mode is independent from the transcription and has distinct regulation. Further, knockdown of TFB2M alone caused significant decrease of 7S DNA, which implies that transcription initiation complexes formed at the LSP engage 7S DNA synthesis more frequently than the initiation of productive replication and transcription.
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    Two carbohydrate recognizing domains from Cycas revoluta leaf lectin show the distinct sugar-binding specificity--A unique mannooligosaccharide recognition by N-terminal domain (2016)
    Oxford University Press
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    Publication Date: 2016-06-25
    Description: Cycas revoluta leaf lectin (CRLL) of mannose-recognizing jacalin-related lectin (mJRL) has two tandem repeated carbohydrate recognition domains, and shows the characteristic sugar-binding specificity toward high mannose-glycans, compared with other mJRLs. We expressed the N-terminal domain and C-terminal domain (CRLL-N and CRLL-C) separately, to determine the fine sugar-binding specificity of each domain, using frontal affinity chromatography, glycan array and equilibrium dialysis. The specificity of CRLL toward high mannose was basically derived from CRLL-N, whereas CRLL-C had affinity for α1-6 extended mono-antennary complex-type glycans. Notably, the affinity of CRLL-N was most potent to one of three Man 8 glycans and Man 9 glycan, whereas the affinity of CRLL-C decreased with the increase in the number of extended α1-2 linked mannose residue. The recognition of the Man 8 glycans by CRLL-N has not been found for other mannose recognizing lectins. Glycan array reflected these specificities of the two domains. Furthermore, it was revealed by equilibrium dialysis method that the each domain had two sugar-binding sites, similar with Banlec, banana mannose-binding Jacalin-related lectin.
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    Three supernova shells around a young M33 star cluster (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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.
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    The origin of the {alpha}-enhancement of massive galaxies (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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.
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    Detection of cyclotron resonance scattering feature in high-mass X-ray binary pulsar SMC X-2 (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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.
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    How similar is the stellar structure of low-mass late-type galaxies to that of early-type dwarfs? (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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.
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    Free-floating planets from core accretion theory: microlensing predictions (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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 .
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    Habitable worlds with JWST: transit spectroscopy of the TRAPPIST-1 system? (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    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.
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    Swift follow-up of the gravitational wave source GW150914 (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    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.
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    Constraining the ellipticity of strongly magnetized neutron stars powering superluminous supernovae (2016)
    Oxford University Press
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    Publication Date: 2016-05-07
    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.
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    No sign (yet) of intergalactic globular clusters in the Local Group (2016)
    Oxford University Press
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    Publication Date: 2016-05-27
    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.
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    Friedmann-Robertson-Walker models do not require zero active mass (2016)
    Oxford University Press
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    Publication Date: 2016-05-27
    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.
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    Is there an exoplanet in the Solar system? (2016)
    Oxford University Press
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    Publication Date: 2016-05-28
    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.
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    Formation of massive Population III galaxies through photoionization feedback: a possible explanation for CR 7 (2016)
    Oxford University Press
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    Publication Date: 2016-05-12
    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.
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  • 88
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    A close look at secular evolution: boxy/peanut bulges reduce gas inflow to the central kiloparsec (2016)
    Oxford University Press
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    Publication Date: 2016-07-09
    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.
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  • 89
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    Three-dimensional orientation of compact high velocity clouds (2016)
    Oxford University Press
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    Publication Date: 2016-07-13
    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.
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  • 90
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    An accretion disc-irradiation hybrid model for the optical/UV variability in radio-quiet quasars (2016)
    Oxford University Press
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    Publication Date: 2016-07-17
    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.
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  • 91
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    No apparent superluminal motion in the first-known jetted tidal disruption event Swift J1644+5734 (2016)
    Oxford University Press
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    Publication Date: 2016-07-17
    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.
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  • 92
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    The Local Group: the ultimate deep field (2016)
    Oxford University Press
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    Publication Date: 2016-07-17
    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.
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  • 93
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    Geometrical beaming of stellar mass ULXs (2016)
    Oxford University Press
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    Publication Date: 2016-07-21
    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.
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  • 94
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    Affinity maturation of a CDR3-grafted VHH using in silico analysis and surface plasmon resonance (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: A requirement for advancing antibody-based medicine is the development of proteins that can bind with high affinity to a specific epitope related to a critical protein activity site. As a part of generating such proteins, we have succeeded in creating a binding protein without changing epitope by complementarity-determining region 3 (CDR3) grafting (Inoue et al. , Affinity transfer to a human protein by CDR3 grafting of camelid VHH. Protein Sci. 20, 1971–1981). However, the affinity of the target-binding protein was low. In this manuscript, the affinity maturation of a target-binding protein was examined using CDR3-grafted camelid single domain antibody (VHH) as a model protein. Several amino acids in the CDR1 and CDR2 regions of VHH were mutated to tyrosines and/or serines and screened for affinity-matured proteins by using in silico analysis. The mutation of two amino acids in the CDR2 region to arginine and/or aspartic acid increased the affinity by decreasing the dissociation rate. The affinity of designed mutant increased by ~20-fold over that of the original protein. In the present study, candidate mutants were narrowed down using in silico screening and computational modelling, thus avoiding much in vitro analytical effort. Therefore, the method used in this study is expected to be one of the useful for promoting affinity maturation of antibodies.
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    Topics: Biology , Chemistry and Pharmacology
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    Characterization of deamidation at Asn138 in L-chain of recombinant humanized Fab expressed from Pichia pastoris (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: A method was previously established for evaluating Asn deamidation by matrix-assisted laser desorption/ionization time of flight-mass spectrometry using endoproteinase Asp-N. In this study, we demonstrated that this method could be applied to the identification of the deamidation site of the humanized fragment antigen-binding (Fab). First, a system for expressing humanized Fab from methylotrophic yeast Pichia pastoris was constructed, resulting in the preparation of ~30 mg of the purified humanized Fab from 1 l culture. Analysis of the L-chain derived from recombinant humanized Fab that was heated at pH 7 and 100°C for 1 h showed the deamidation at Asn138 in the constant region. Then, we prepared L-N138D Fab and L-N138A Fab and examined their properties. The circular dichroism (CD) spectrum of the L-N138D Fab was partially different from that of the wild-type Fab. The measurement of the thermostability showed that L-N138D caused a significant decrease in the thermostability of Fab. On the other hand, the CD spectrum and thermostability of L-N138A Fab showed the same behaviour as the wild-type Fab. Thus, it was suggested that the introduction of a negative charge at position 138 in the L-chain by the deamidation significantly affected the stability of humanized Fab.
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    TRIM proteins as trim tabs for the homoeostasis (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: The tripartite motif (TRIM) or RBCC proteins are characterized by the TRIM composed of a RING finger, B-box and coiled-coil domains. TRIM proteins often play roles in the post-translational protein modification, including ubiquitylation and other ubiquitin-like modifications. Evidence has accumulated in regard to the contribution of TRIM proteins to diverse cellular processes, including such as cell cycle progression, apoptosis, immunity and transcriptional regulation. In particular, some of the TRIM proteins have been characterized to exert oncogenic or tumour suppressor-like functions depending on the context. A recent report by Inoue and his colleagues has revealed that Terf/TRIM17 stimulates the degradation of a kinetochore protein ZWINT and regulates the proliferation of breast cancer cells. Terf has also been paid attention as a factor promoting neuronal apoptosis, by degrading a Bcl2-like anti-apoptotic protein Mcl-1. Like aircraft trim tabs, TRIM proteins trim the balance of homoeostasis by modulating various biological pathways through protein–protein interactions.
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    Inhibition of DNA binding of MCM2-7 complex by phosphorylation with cyclin-dependent kinases (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: Cyclin-dependent kinase (CDK) that plays a central role in preventing re-replication of DNA phosphorylates several replication proteins to inactivate them. MCM4 in MCM2-7 and RPA2 in RPA are phosphorylated with CDK in vivo . There are inversed correlations between the phosphorylation of these proteins and their chromatin binding. Here, we examined in vitro phosphorylation of human replication proteins of MCM2-7, RPA, TRESLIN, CDC45 and RECQL4 with CDK2/cyclinE, CDK2/cyclinA, CDK1/cyclinB, CHK1, CHK2 and CDC7/DBF4 kinases. MCM4, RPA2, TRESLIN and RECQL4 were phosphorylated with CDKs. Effect of the phosphorylation by CDK2/cyclinA on DNA-binding abilities of MCM2-7 and RPA was examined by gel-shift analysis. The phosphorylation of RPA did not affect its DNA-binding ability but that of MCM4 inhibited the ability of MCM2-7. Change of six amino acids of serine and threonine to alanines in the amino-terminal region of MCM4 rendered the mutant MCM2-7 insensitive to the inhibition with CDK. These biochemical data suggest that phosphorylation of MCM4 at these sites by CDK plays a direct role in dislodging MCM2-7 from chromatin and/or preventing re-loading of the complex to chromatin.
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    Effects of alcohols on the stability and low-frequency local motions that control the slow changes in structural dynamics of ferrocytochrome c (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: To determine the effects of alcohols on the low-frequency local motions that control slow changes in structural dynamics of native-like compact states of proteins, we have studied the effects of alcohols on structural fluctuation of M80-containing -loop by measuring the rate of thermally driven CO dissociation from a natively folded carbonmonoxycytochrome c under varying concentrations of alcohols (methanol, ethanol, 1-propanol, 2-propanol, 3°-butanol, 2,2,2-trifluoroethanol). As alcohol is increased, the rate coefficient of CO dissociation ( k diss ) first decreases in subdenaturing region and then increases on going from subdenaturing to denaturing milieu. This decrease in k diss is more for 2,2,2-trifluroethanol and 1-propanol and least for methanol, indicating that the first phase of motional constraint is due to the hydrophobicity of alcohols and intramolecular protein cross-linking effect of alcohols, which results in conformational entropy loss of protein. The thermal denaturation midpoint for ferrocytochrome c decreases with increase in alcohol, indicating that alcohol decrease the global stability of protein. The stabilization free energy ( G ) in alcohols’ solution was calculated from the slope of the Wyman–Tanford plot and water activity. The m -values obtained from the slope of G versus alcohols plot were found to be more negative for longer and linear chain alcohols, indicating destabilization of proteins by alcohols through disturbance of hydrophobic interactions and hydrogen bonding.
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    Linear ubiquitination-mediated NF-{kappa}B regulation and its related disorders (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: Ubiquitination is a post-translational modification involved in the regulation of a broad variety of cellular functions, such as protein degradation and signal transduction, including nuclear factor-B (NF-B) signalling. NF-B is crucial for inflammatory and immune responses, and aberrant NF-B signalling is implicated in multiple disorders. We found that linear ubiquitin chain assembly complex (LUBAC), composed of HOIL-1L, HOIP and SHARPIN, generates a novel type of Met1 (M1)-linked linear polyubiquitin chain and specifically regulates the canonical NF-B pathway. Moreover, specific deubiquitinases, such as CYLD, A20 (TNFAIP3) and OTULIN/gumby, inhibit LUBAC-induced NF-B activation by different molecular mechanisms, and several M1-linked ubiquitin-specific binding domains have been structurally defined. LUBAC and these linear ubiquitination-regulating factors contribute to immune and inflammatory processes and apoptosis. Functional impairments of these factors are correlated with multiple disorders, including autoinflammation, immunodeficiencies, dermatitis, B-cell lymphomas and Parkinson’s disease. This review summarizes the molecular basis and the pathophysiological implications of the linear ubiquitination-mediated NF-B activation pathway regulation by LUBAC.
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    Different circadian expression of major matrix-related genes in various types of cartilage: modulation by light-dark conditions (2013)
    Oxford University Press
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    Publication Date: 2013-10-02
    Description: We screened circadian-regulated genes in rat cartilage by using a DNA microarray analysis. In rib growth-plate cartilage, numerous genes showed statistically significant circadian mRNA expression under both 12:12 h light–dark and constant darkness conditions. Type II collagen and aggrecan genes—along with several genes essential for post-translational modifications of collagen and aggrecan, including prolyl 4-hydroxylase 1, lysyl oxidase, lysyl oxidase-like 2 and 3'-phosphoadenosine 5'-phosphosulphate synthase 2—showed the same circadian phase. In addition, the mRNA level of SOX9, a master transcription factor for the synthesis of type II collagen and aggrecan, has a similar phase of circadian rhythms. The circadian expression of the matrix-related genes may be critical in the development and the growth of various cartilages, because similar circadian expression of the matrix-related genes was observed in hip joint cartilage. However, the circadian phase of the major matrix-related genes in the rib permanent cartilage was almost the converse of that in the rib growth-plate cartilage under light–dark conditions. We also found that half of the oscillating genes had conserved clock-regulatory elements, indicating contribution of the elements to the clock outputs. These findings suggest that the synthesis of the cartilage matrix macromolecules is controlled by cell-autonomous clocks depending upon the in vivo location of cartilage.
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