Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein ...O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases.
ABSTRACT
NGC 1313 X-2 is one of the few known pulsating ultraluminous X-ray sources (PULXs), and so is thought to contain a neutron star that accretes at highly super-Eddington rates. However, the ...physics of this accretion remains to be determined. Here, we report the results of two simultaneous XMM–Newton and HST observations of this PULX taken to observe two distinct X-ray behaviours as defined from its Swift light curve. We find that the X-ray spectrum of the PULX is best described by the hard ultraluminous regime during the observation taken in the lower flux, lower variability amplitude behaviour; its spectrum changes to a broadened disc during the higher flux, higher variability amplitude epoch. However, we see no accompanying changes in the optical/UV fluxes, with the only difference being a reduction in flux in the near-infrared (NIR) as the X-ray flux increased. We attempt to fit irradiation models to explain the UV/optical/IR fluxes but they fail to provide meaningful constraints. Instead, a physical model for the system leads us to conclude that the optical light is dominated by a companion O/B star, albeit with an IR excess that may be indicative of a jet. We discuss how these results may be consistent with the precession of the inner regions of the accretion disc leading to changes in the observed X-ray properties, but not the optical, and whether we should expect to observe reprocessed emission from ULXs.
We present an analysis of the extreme obscuration variability observed during an XMM–Newton 5-d continuous monitoring of the active galactic nuclei (AGN) in NGC 1365. The source was in a ...reflection-dominated state in the first ∼1.5 d, then a strong increase in the 7—10 keV emission was observed in ∼10 h, followed by a symmetric decrease. The spectral analysis of the different states clearly shows that this variation is due to an uncovering of the X-ray source. From this observation, we estimate a size of the X-ray source DS < 1013 cm, a distance of the obscuring clouds R∼ 1016 cm and a density n∼ 1011 cm−3. These values suggest that the X-ray absorption/reflection originates from the broad-line region clouds. This is also supported by the resolved width of the iron narrow Kα emission line, consistent with the width of the broad Hβ line.
ABSTRACT
Ultraluminous X-ray sources (ULXs) provide a unique opportunity to probe the geometry and energetics of super-Eddington accretion. The radiative processes involved in super-Eddington ...accretion are not well understood, and so studying correlated variability between different energy bands can provide insights into the causal connection between different emitting regions. We present a spectral-timing analysis of NGC 1313 X-1 from a recent XMM–Newton campaign. The spectra can be decomposed into two thermal-like components, the hotter of which may originate from the inner accretion disc, and the cooler from an optically thick outflow. We find correlated variability between hard (2–10 keV) and soft (0.3–2 keV) bands on kilosecond time-scales, and find a soft lag of ∼150 s. The covariance spectrum suggests that emission contributing to the lags is largely associated with the hotter of the two thermal-like components, likely originating from the inner accretion flow. This is only the third ULX to exhibit soft lags. The lags range over three orders of magnitude in amplitude, but all three are ∼5–20 per cent of the corresponding characteristic variability time-scales. If these soft lags can be understood in the context of a unified picture of ULXs, then lag time-scales may provide constraints on the density and extent of radiatively driven outflows.
ABSTRACT
Tracking the motions of transient jets launched by low-mass X-ray binaries (LMXBs) is critical for determining the moment of jet ejection, and identifying any corresponding signatures in the ...accretion flow. However, these jets are often highly variable and can travel across the resolution element of an image within a single observation, violating a fundamental assumption of aperture synthesis. We present a novel approach in which we directly fit a single time-dependent model to the full set of interferometer visibilities, where we explicitly parametrize the motion and flux density variability of the emission components, to minimize the number of free parameters in the fit, while leveraging information from the full observation. This technique allows us to detect and characterize faint, fast-moving sources, for which the standard time binning technique is inadequate. We validate our technique with synthetic observations, before applying it to three Very Long Baseline Array (VLBA) observations of the black hole candidate LMXB MAXI J1803−298 during its 2021 outburst. We measured the proper motion of a discrete jet component to be 1.37 ± 0.14 mas h−1, and thus we infer an ejection date of MJD $59348.08_{-0.06}^{+0.05}$, which occurs just after the peak of a radio flare observed by the Australia Telescope Compact Array (ATCA) and the Atacama Large Millimeter/Sub-Millimeter Array (ALMA), while MAXI J1803−298 was in the intermediate state. Further development of these new VLBI analysis techniques will lead to more precise measurements of jet ejection dates, which, combined with dense, simultaneous multiwavelength monitoring, will allow for clearer identification of jet ejection signatures in the accretion flow.
High altitude pregnancy is associated with increased frequency of low birth weight infants and neonatal complications, the risks of which are higher in women of low‐altitude ancestry. Does ancestry ...also influence the risk of miscarriage (pregnancy loss <20 weeks) in high‐altitude pregnancy? To answer this, 5386 women from La Paz, Bolivia (3300‐4150 m) with ≥1 live‐born infant were identified. Data were extracted from medical records including maternal and paternal ancestry, demographic factors, and reproductive history. The risk of miscarriage by ancestry was assessed using multivariate logistic regression, adjusting for parity, and maternal age. Andean women experienced first live‐births younger than Mestizo or European women (21.7 ± 4.6 vs 23.4 ± 8.0 vs 24.1 ± 5.1, P < .001). Andeans experienced more pregnancies per year of reproductive life (P < .001) and had significantly higher ratios of live‐births to miscarriages than women of Mestizo or European ancestry (P < .001). Andean women were 24% less likely to have ever experienced a miscarriage compared to European women (OR:0.76; CI:0.62‐0.90, P < .001). The woman's partner's ancestry wasn't a significant independent predictor of miscarriage. In conclusion, the risk of miscarriage at high altitude is lower in Andean women. The lack of a paternal ancestry effect suggests underlying mechanisms relate more to differential maternal adaptation in early pregnancy than fetal genetics.
The late Jurassic–early Cretaceous is commonly considered the only cold climatic interval in Earth history without any direct evidence of polar ice. A newly discovered dropstone-bearing interval from ...the subtropical Iberian Basin (western Tethys) is described and provides evidence of contemporaneous polar glaciation. This interval is correlated laterally for 4.8km and contains a boulder and two cobble-sized quartzite dropstones that are encased in mid-Cretaceous fissile black shales and fine-grained sandstones. Based on previously published dimensions of similar large clasts, only glacial dropstones and impact ejecta blocks reach the dimensions of the boulder-sized dropstone reported from Iberia. The dropstones show morphological features compatible with glacial transport and abrasion in a subglacial setting which closely resembles the features observed in recent glacial boulders exposed near the snouts of glaciers in Iceland. These Late Aptian dropstones from Spain correlate with many other similar erratics in the northern and southern palaeohemispheres, and suggest that ice sheets formed around the palaeo-North Pole during certain periods of the early Cretaceous. Our results and associated evidence such as the occurrence of glendonites, tillites, moderate- to high-amplitude sea-level oscillations worldwide, minimum pCO2 concentrations, variation in calcareous nannofossil assemblages from low and high latitudes and isotopic excursions suggest that during the mid-Cretaceous there were periods of ice growth and decay that influenced the palaeotemperature, palaeoecology and sedimentology of the marine realm. The new data from Iberia are supported by recent results from Arctic Canada that indicate cool shelves and a mid-Cretaceous cold snap that developed for ~6Myr between 118 and 112Ma. The late Aptian dropstones reported in eastern Iberia were likely transported from high northern latitudes towards subtropical ones in the western Tethys by an extreme iceberg drift similar to those occurring at the present day in the Atlantic Ocean. Icebergs released from a northern fringing ice sheet may have travelled southwards through the Greenland–Norwegian Seaway.
•The biggest late Aptian dropstone reported from the palaeo-Northern Hemisphere.•The southernmost Cretaceous dropstones reported from the palaeo-Northern Hemisphere.•Glacial dropstones contains glacial features similar to Iceland glacial boulders.•Late Aptian Arctic ice-volcanic interactions released overturned icebergs.•Overturned icebergs from Arctic ice sheets reached subtropical latitudes.
Abstract
We study the spectral evolution of the black hole candidate EXO 1846−031 during its 2019 outburst, in the 1–150 keV band, with the Hard X-ray Modulation Telescope. The continuum spectrum is ...well modeled with an absorbed disk-blackbody plus cutoff power law, in the hard, intermediate, and soft states. In addition, we detect an ≈6.6 keV Fe emission line in the hard intermediate state. Throughout the soft intermediate and soft states, the fitted inner disk radius remains almost constant; we suggest that it has settled at the innermost stable circular orbit (ISCO). However, in the hard and hard intermediate states, the apparent inner radius was unphysically small (smaller than the ISCO), even after accounting for the Compton scattering of some of the disk photons by the corona in the fit. We argue that this is the result of a high hardening factor,
f
col
≈ 2.0–2.7, in the early phases of the outburst evolution, well above the canonical value of 1.7 suitable for a steady disk. We suggest that the inner disk radius was already close to the ISCO in the low/hard state. Furthermore, we propose that this high value of the hardening factor in the relatively hard state was probably caused by the additional illuminating of the coronal irradiation onto the disk. Additionally, we estimate the spin parameter using the continuum-fitting method, over a range of plausible black hole masses and distances. We compare our results with the spin measured using the reflection-fitting method and find that the inconsistency of the two results is partly caused by different choices of
f
col
.
Context.
It is thought that ultraluminous X-ray sources (ULXs) are mainly powered by super-Eddington accreting neutron stars or black holes as shown by the recent discovery of X-ray pulsations and ...relativistic winds.
Aims.
This work presents a follow-up study of the spectral evolution over two decades of the pulsing ULX NGC 1313 X-2 in order to understand the structure of the accretion disc. The primary objective is to determine the shape and nature of the dominant spectral components by investigating their variability with the changes in the source luminosity.
Methods.
We performed a spectral analysis over the canonical 0.3–10.0 keV energy band of all the high signal-to-noise
XMM-Newton
observations (96% of the available data), and we tested a number of different spectral models, which should approximate super-Eddington accretion discs. The baseline model consists of two thermal blackbody components with different temperatures plus an exponential cutoff powerlaw.
Results.
The baseline model provides a good description of the X-ray spectra. In particular, the hotter and brighter (
L
X
∼ 6–9 × 10
39
erg s
−1
) thermal component describes the emission from the super-Eddington inner disc and the cutoff powerlaw describes the contribution from the accretion column of the neutron star. Instead, the cooler component describes the emission from the outer region of the disc close to the spherisation radius and the wind. The luminosity-temperature relation for the cool component follows a negative trend, which is not consistent with
L
∝
T
4
, as is expected from a sub-Eddington thin disc of Shakura-Sunayev. This is not consistent with
L
∝
T
2
either, as is expected for an advection-dominated disc. However, this would rather agree with a wind-dominated X-ray emitting region. Instead, the (
L
x
,
T
disk
) relation for the hotter component is somewhere in between the first two theoretical scenarios.
Conclusions.
Our findings agree with the super-Eddington scenario and provide further detail on the disc structure. The source spectral evolution is qualitatively similar to that seen in NGC 1313 X-1 and Holmberg IX X-1, indicating a common structure and evolution among archetypal ULXs.
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