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  • 1
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    FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response (2014)
    Oxford University Press
    Details
    Publication Date: 2014-10-10
    Description: Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. However, the E3 ligase that targets hSSB1 for destruction is still unknown. Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation. Furthermore, cells overexpression of Fbxl5 abrogated the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets and exhibited increased radiosensitivity, chemosensitivity and defective checkpoint activation after genotoxic stress stimuli. Moreover, the protein levels of hSSB1 and Fbxl5 showed an inverse correlation in lung cancer cells lines and clinical lung cancer samples. Therefore, Fbxl5 may negatively modulate hSSB1 to regulate DNA damage response, implicating Fbxl5 as a novel, promising therapeutic target for lung cancers.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice (2015)
    Oxford University Press
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    Publication Date: 2015-05-09
    Description: Fabry disease is caused by deficient activity of lysosomal enzyme α-galactosidase A. The enzyme deficiency results in intracellular accumulation of glycosphingolipids, leading to a variety of clinical manifestations including hypertrophic cardiomyopathy and renal insufficiency. The mechanism through which glycosphingolipid accumulation causes these manifestations remains unclear. Current treatment, especially when initiated at later stage of the disease, does not produce completely satisfactory results. Elucidation of the pathogenesis of Fabry disease is therefore crucial to developing new treatments. We found increased activity of androgen receptor (AR) signaling in Fabry disease. We subsequently also found that blockade of AR signaling either through castration or AR-antagonist prevented and reversed cardiac and kidney hypertrophic phenotype in a mouse model of Fabry disease. Our findings implicate abnormal AR pathway in the pathogenesis of Fabry disease and suggest blocking AR signaling as a novel therapeutic approach.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Observable fractions of core-collapse supernova light curves brightened by binary companions (2015)
    Oxford University Press
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    Publication Date: 2015-05-14
    Description: Many core-collapse supernova progenitors are presumed to be in binary systems. If a star explodes in a binary system, the early supernova light curve can be brightened by the collision of the supernova ejecta with the companion star. The early brightening can be observed when the observer is in the direction of the hole created by the collision. Based on a population synthesis model, we estimate the fractions of core-collapse supernovae in which the light-curve brightening by the collision can be observed. We find that 0.19 per cent of core-collapse supernova light curves can be observed with the collisional brightening. Type Ibc supernova light curves are more likely to be brightened by the collision (0.53 per cent) because of the high fraction of the progenitors being in binary systems and their proximity to the companion stars. Type II and IIb supernova light curves are less affected (~10 –3 and ~10 –2 per cent, respectively). Although the early, slow light-curve declines of some Type IIb and Ibc supernovae are argued to be caused by the collision with the companion star (e.g. SN 2008D), the small expected fraction, as well as the unrealistically small separation required, disfavour the argument. The future transient survey by the Large Synoptic Survey Telescope is expected to detect ~10 Type Ibc supernovae with the early collisional brightening per year, and they will be able to provide information on supernova progenitors in binary systems.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    X-ray fluorescent lines from the Compton-thick AGN in M51 (2015)
    Oxford University Press
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    Publication Date: 2015-10-22
    Description: The cold disc/torus gas surrounding active galactic nuclei (AGN) emits fluorescent lines when irradiated by hard X-ray photons. The fluorescent lines of elements other than Fe and Ni are rarely detected due to their relative faintness. We report the detection of Kα lines of neutral Si, S, Ar, Ca, Cr, and Mn, along with the prominent Fe Kα, Fe Kβ, and Ni Kα lines, from the deep Chandra observation of the low-luminosity Compton-thick AGN in M51. The Si Kα line at 1.74 keV is detected at ~3, the other fluorescent lines have a significance between 2 and 2.5 , while the Cr line has a significance of ~1.5. These faint fluorescent lines are made observable due to the heavy obscuration of the intrinsic spectrum of M51, which is revealed by NuSTAR observation above 10 keV. The hard X-ray continuum of M51 from Chandra and NuSTAR can be fitted with a power-law spectrum with an index of 1.8, reprocessed by a torus with an equatorial column density of N H  ~ 7  x  10 24  cm –2 and an inclination angle of 74°. This confirms the Compton-thick nature of the nucleus of M51. The relative element abundances inferred from the fluxes of the fluorescent lines are similar to their solar values, except for Mn, which is about 10 times overabundant. It indicates that Mn is likely enhanced by the nuclear spallation of Fe.
    Print ISSN: 1745-3925
    Electronic ISSN: 1745-3933
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    Optical observations of an SN 2002cx-like peculiar supernova SN 2013en in UGC 11369 (2015)
    Oxford University Press
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    Publication Date: 2015-07-10
    Description: We present optical observations of an SN 2002cx-like supernova SN 2013en in UGC 11369, spanning from a phase near maximum light ( t = + 1 d) to t = + 60 d with respect to the R -band maximum. Adopting a distance modulus of μ = 34.11 ± 0.15 mag and a total extinction (host galaxy+Milky Way) of A V 1.5 mag, we found that SN 2013en peaked at M R –18.6 mag, which is underluminous compared to the normal SNe Ia. The near maximum spectra show lines of Si  ii , Fe  ii , Fe  iii , Cr  ii , Ca  ii and other intermediate-mass and iron group elements which all have lower expansion velocities (i.e. ~ 6000 km s – 1 ). The photometric and spectroscopic evolution of SN 2013en is remarkably similar to those of SN 2002cx and SN 2005hk, suggesting that they are likely to be generated from a similar progenitor scenario or explosion mechanism.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    Early ultraviolet signatures from the interaction of Type Ia supernova ejecta with a stellar companion (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-03
    Description: The progenitors of Type Ia supernovae (SNe Ia) are not yet fully understood. The two leading progenitor scenarios are the single-degenerate (SD) scenario and the double-degenerate scenario. In the SD scenario, the collision of the SN Ia ejecta with its companion star is expected to produce detectable ultraviolet (UV) emission in the first few days after the SN explosion within certain viewing angles. A strong UV flash has recently been detected in an SN 2002es-like peculiar SN Ia iPTF14atg by Cao et al., which is interpreted as evidence of an early-time UV signature due to SN ejecta interacting with its companion star, supporting the SD scenario. In this paper, we present the expected luminosity distributions of early-time UV emission arising from SN Ia ejecta–companion interaction by performing binary population synthesis calculations for different progenitor systems in the SD scenario. Our theoretical predictions will be helpful for future early-time observations of SNe Ia to constrain their possible progenitors. Assuming the observed strong UV pulse of iPTF14atg was indeed produced by the SN ejecta–companion interaction, our population synthesis model suggests that the progenitor system of iPTF14atg is most likely a red-giant donor binary system, and it is unlikely to have been a main-sequence or helium-star donor system.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Geography, trade and regional development: the role of wage costs, exchange rates and currency/capital movements (2014)
    Oxford University Press
    Details
    Publication Date: 2014-10-09
    Description: Existing theories of geographical specialization and trade can be classified into four groups: supply-side; demand-side; endogenous growth and institutional models. In the recent past, economic geographers have paid little attention to earlier regional economic analysis and concentrated for the most part on detailed examination of production structures, the chains linking upstream and downstream activities into production and value networks, clusters, institutions and more recently, economic evolution. As a result, existing economic geography is ill-equipped to deal with the impact of some aspects of the evolution of costs, exchange rates, trade and capital flows on regional development and pays relatively little attention to economic calculation. Geographical economics includes an underlying theory of trade and micro-foundations, yet its supply-side approach neglects the role of monetary and demand-side (except in gravity models of trade) factors. The aim of this article is to argue for an extension of existing theoretical frameworks to embrace these issues in the light of recent trends in global economic geography and successive financial and debt crises that have stricken the developed world.
    Keywords: F10 - General, F11 - Neoclassical Models of Trade, F13 - Trade Policy ; International Trade Organizations, F21 - International Investment ; Long-Term Capital Movements, F31 - Foreign Exchange, F32 - Current Account Adjustment ; Short-Term Capital Movements, O10 - General, R10 - General, R11 - Regional Economic Activity: Growth, Development, and Changes
    Print ISSN: 1468-2702
    Electronic ISSN: 1468-2710
    Topics: Geography , Economics
    Published by Oxford University Press
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  • 8
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    On the evolution of rotating accreting white dwarfs and Type Ia supernovae (2014)
    Oxford University Press
    Details
    Publication Date: 2014-10-18
    Description: The potential importance of the angular momentum which is gained by accreting white dwarfs (WDs) has been increasingly recognized in the context of Type Ia supernova (SN Ia) single-degenerate model. The expectation that the spin of the WD can delay the explosion should help the single-degenerate model to be consistent with the observed properties of most SNe Ia, in particular by avoiding hydrogen contamination. In this paper, we attempt to study the most prominent single-degenerate supersoft (WD + MS) channel when the rotation of accreting WDs is considered. We present a detailed binary population synthesis study to examine the predicted population of SNe Ia for this channel. For our standard model, we find that 77 per cent of these SNe Ia explode with WD masses which are low enough to be supported by solid-body rotation ( ≤ 1.5 M ); this is a substantially higher proportion than found by previous work. Only 2 per cent have WD explosion masses ≥2.0 M ; these require the initial WD mass to be larger than 1.0 M . We further discuss the possible origin of the diversity of SNe Ia from the pre- and post-accretion properties of the WDs in this population. We also suggest that some SN Ia progenitors with substantial circumstellar hydrogen, including some apparent Type IIn SNe, might be related to WDs which required support from differential rotation to avoid explosion, since these can still be accreting from hydrogen-rich donors with a relatively high mass-transfer rate at the time of the SN explosion.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Constraining the progenitor of the Type Ia Supernova SN 2012cg (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-29
    Description: The nature of the progenitors of Type Ia supernovae (SNe Ia) is not yet fully understood. In the single-degenerate (SD) scenario, the collision of the SN ejecta with its companion star is expected to produce detectable ultraviolet emission in the first few days after the SN explosion within certain viewing angles. It was recently found that the B – V colour of the nearby SN Ia SN 2012cg at about 16 d before the maximum B -band brightness was about 0.2 mag bluer than those of other normal SNe Ia, which was reported as the first evidence for excess blue light from the interaction of normal SN Ia ejecta with its companion star. In this work, we compare current observations for SN 2012cg from its pre-explosion phase to the late-time nebular phase with theoretical predictions from binary evolution and population synthesis calculations for a variety of popular progenitor scenarios. We find that a main-sequence donor or a carbon–oxygen white dwarf donor binary system is more likely to be the progenitor of SN 2012cg. However, both scenarios also predict properties which are in contradiction to the observed features of this system. Taking both theoretical and observational uncertainties into account, we suggest that it might be too early to conclude that SN 2012cg was produced from an explosion of a Chandrasekhar-mass white dwarf in the SD scenario. Future observations and improved detailed theoretical modelling are still required to place a more stringent constraint on the progenitor of SN 2012cg.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    RUNX2 mutation impairs bone remodelling of dental follicle cells and periodontal ligament cells in patients with cleidocranial dysplasia (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-21
    Description: RUNX2 is an important osteo-specific factor with crucial functions in bone formation and remodelling as well as resorption of teeth. Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth. In our study, dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were isolated, cultured and identified from one patient with CCD and compared with normal controls. This CCD patient was confirmed to have a heterozygous frameshift mutation of RUNX2 (c.514delT, p.Ser172fs) in the previous study. The results showed that the proliferation abilities of DFCs and PDLCs were both disturbed by the RUNX2 mutation in the CCD patient compared with the normal control. A co-culture system of these cells with human peripheral blood mononuclear cells was then used to investigate the effect of RUNX2 mutation on osteoclastogenesis. We found that the RUNX2 mutation in CCD reduced the expression of osteoclast-related genes, such as RUNX2 , CTR , CTSK , RANKL and OPG . The ability of osteoclastogenesis in DFCs and PDLCs detected by tartrate-resistant acid phosphatase staining in the co-culture system was also reduced by the RUNX2 mutation compared with the normal control. These outcomes indicate that the RUNX2 mutation disturbs the modulatory effects of DFCs and PDLCs on the differentiation of osteoclasts and osteoblasts, thereby interfering with bone remodelling. These effects may contribute in part to the pathological manifestations of retention of primary teeth and delayed eruption of permanent teeth in patients with CCD.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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