Human carbonyl reductase 1 (hCBR1) is an NADPH-dependent short chain dehydrogenase/reductase with broad substrate specificity and is thought to be responsible for the in vivo reduction of quinones, ...prostaglandins, and other carbonyl-containing compounds including xenobiotics. In addition, hCBR1 possesses a glutathione binding site that allows for increased affinity toward GSH-conjugated molecules. It has been suggested that the GSH-binding site is near the active site; however, no structures with GSH or GSH conjugates have been reported. We have solved the x-ray crystal structures of hCBR1 and a substrate mimic in complex with GSH and the catalytically inert GSH conjugate hydroxymethylglutathione (HMGSH). The structures reveal the GSH-binding site and provide insight into the affinity determinants for GSH-conjugated substrates. We further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione, is an ideal hCBR1 substrate (Km = 30 μm, kcat = 450 min-1) with kinetic constants comparable with the best known hCBR1 substrates. Furthermore, we demonstrate that hCBR1 dependent GSNO reduction occurs in A549 lung adenocarcinoma cell lysates and suggest that hCBR1 may be involved in regulation of tissue levels of GSNO.
Context.
The sub-Jovian, or Neptunian, desert is a previously identified region of parameter space where there is a relative dearth of intermediate-mass planets with short orbital periods.
Aims.
We ...present the discovery of a new transiting planetary system within the Neptunian desert, NGTS-14.
Methods.
Transits of NGTS-14Ab were discovered in photometry from the Next Generation Transit Survey (NGTS). Follow-up transit photometry was conducted from several ground-based facilities, as well as extracted from TESS full-frame images. We combine radial velocities from the HARPS spectrograph with the photometry in a global analysis to determine the system parameters.
Results.
NGTS-14Ab has a radius that is about 30 per cent larger than that of Neptune (0.444 ± 0.030
R
Jup
) and is around 70 per cent more massive than Neptune (0.092 ± 0.012
M
Jup
). It transits the main-sequence K1 star, NGTS-14A, with a period of 3.54 days, just far away enough to have maintained at least some of its primordial atmosphere. We have also identified a possible long-period stellar mass companion to the system, NGTS-14B, and we investigate the binarity of exoplanet host stars inside and outside the Neptunian desert using
Gaia
.
Several studies have documented periodic and quasi-periodic signals from the time series of dMe flare stars and other stellar sources. Such periodic signals, observed within quiescent phases (i.e., ...devoid of larger-scale microflare or flare activity), range in a period from 1 to 1000 s and hence have been tentatively linked to ubiquitous p-mode oscillations generated in the convective layers of the star. As such, most interpretations for the observed periodicities have been framed in terms of magnetohydrodynamic wave behavior. However, we propose that a series of continuous nanoflares, based upon a power-law distribution, can provide a similar periodic signal in the associated time series. Adapting previous statistical analyses of solar nanoflare signals, we find the first statistical evidence for stellar nanoflare signals embedded within the noise envelope of M-type stellar lightcurves. Employing data collected by the Next Generation Transit Survey (NGTS), we find evidence for stellar nanoflare activity demonstrating a flaring power-law index of 3.25 0.20, alongside a decay timescale of 200 100 s. We also find that synthetic time series, consistent with the observations of dMe flare star lightcurves, are capable of producing quasi-periodic signals in the same frequency range as p-mode signals, despite being purely composed of impulsive signatures. Phenomena traditionally considered a consequence of wave behavior may be described by a number of high-frequency but discrete nanoflare energy events. This new physical interpretation presents a novel diagnostic capability, by linking observed periodic signals to given nanoflare model conditions.
ABSTRACT
Light curves of the accreting white dwarf pulsator GW Librae spanning a 7.5-month period in 2017 were obtained as part of the Next-Generation Transit Survey. This data set comprises 787 h of ...photometry from 148 clear nights, allowing the behaviour of the long (hours) and short-period (20 min) modulation signals to be tracked from night to night over a much longer observing baseline than has been previously achieved. The long-period modulations intermittently detected in previous observations of GW Lib are found to be a persistent feature, evolving between states with periods ≃ 83 min and 2–4 h on time-scales of several days. The 20 min signal is found to have a broadly stable amplitude and frequency for the duration of the campaign, but the previously noted phase instability is confirmed. Ultraviolet observations obtained with the Cosmic Origin Spectrograph on-board the Hubble Space Telescope constrain the ultraviolet-to-optical flux ratio to ≃5 for the 4 h modulation, and ≲1 for the 20 min period, with caveats introduced by non-simultaneous observations. These results add further observational evidence that these enigmatic signals must originate from the white dwarf, highlighting our continued gap in theoretical understanding of the mechanisms that drive them.
Context
Fatigue risk management (FRM) strategies offer a potential solution to the widespread problem of fatigued trainees in the clinical workplace. These strategies assume a shared perception that ...fatigue is hazardous. Despite the growing body of evidence suggesting that fatigue leads to burnout and medical errors, previous research suggests that residents perceive fatigue as a personal, surmountable burden rather than an occupational hazard. Before we can implement FRM, we need a better understanding of when and how such problematic notions of fatigue are adopted by medical trainees. Thus, we sought to explore how third‐year medical students understand and manage the workplace fatigue they experience during their first year of clinical rotations.
Methods
A total of 22 third‐year medical students participated in semi‐structured interviews exploring their perspectives of workplace fatigue. Data collection and analysis occurred iteratively in keeping with constructivist grounded theory methodology and were informed by theoretical sampling to sufficiency.
Results
Our participants described unprecedented levels of sleep deprivation combined with uncertainty and confusion that led to significant fatigue during training. Drawing on their workplace experience, trainees believed that fatigue posed three distinct threats, which evoked different coping strategies: (i) threat to personal health, managed by perseverance; (ii) threat to patients, managed by faith in the system, and (iii) threat to professional reputation, managed by stoicism.
Conclusions
Our findings highlight how senior medical students grapple with fatigue, as they understand it, within a training context in which they are expected to deny the impact of their fatigue on patients and themselves. Despite empirical evidence to the contrary, the prevailing assumption amongst our participants is that an ability to withstand sleep deprivation without impairment will develop naturally over time. Efforts to implement FRM strategies will need to address this assumption if these strategies are to be successfully taken up and effective.
Medical students attempt to manage workplace fatigue through perseverance, faith in the system and stoicism – strategies that are at odds with fatigue risk management approaches in other high‐stakes industries. Is it time to re‐calibrate how we understand, discuss and role‐model fatigue management in medicine?
Abstract
PDS 110 is a young disc-hosting star in the Orion OB1A association. Two dimming events of similar depth and duration were seen in 2008 (WASP) and 2011 (KELT), consistent with an object in a ...closed periodic orbit. In this paper, we present data from a ground-based observing campaign designed to measure the star both photometrically and spectroscopically during the time of predicted eclipse in 2017 September. Despite high-quality photometry, the predicted eclipse did not occur, although coherent structure is present suggesting variable amounts of stellar flux or dust obscuration. We also searched for radial velocity (RV) oscillations caused by any hypothetical companion and can rule out close binaries to 0.1Ms. A search of Sonneberg plate archive data also enabled us to extend the photometric baseline of this star back more than 50 yr, and similarly does not re-detect any deep eclipses. Taken together, they suggest that the eclipses seen in WASP and KELT photometry were due to aperiodic events. It would seem that PDS 110 undergoes stochastic dimmings that are shallower and of shorter duration than those of UX Ori variables, but may have a similar mechanism.
We report the confirmation and mass determination of three hot Jupiters discovered by the Transiting Exoplanet Survey Satellite (TESS) mission: HIP 65Ab (TOI-129, TIC-201248411) is an ...ultra-short-period Jupiter orbiting a bright (V = 11.1 mag) K4-dwarf every 0.98 days. It is a massive 3.213 ± 0.078 MJ planet in a grazing transit configuration with an impact parameter of b = 1.17−0.08+0.10. As a result the radius is poorly constrained, 2.03−0.49+0.61RJ. The planet’s distance to its host star is less than twice the separation at which it would be destroyed by Roche lobe overflow. It is expected to spiral into HIP 65A on a timescale ranging from 80 Myr to a few gigayears, assuming a reduced tidal dissipation quality factor of Qs′ = 107 − 109. We performed a full phase-curve analysis of the TESS data and detected both illumination- and ellipsoidal variations as well as Doppler boosting. HIP 65A is part of a binary stellar system, with HIP 65B separated by 269 AU (3.95 arcsec on sky). TOI-157b (TIC 140691463) is a typical hot Jupiter with a mass of 1.18 ± 0.13 MJ and a radius of 1.29 ± 0.02 RJ. It has a period of 2.08 days, which corresponds to a separation of just 0.03 AU. This makes TOI-157 an interesting system, as the host star is an evolved G9 sub-giant star (V = 12.7). TOI-169b (TIC 183120439) is a bloated Jupiter orbiting a V = 12.4 G-type star. It has a mass of 0.79 ±0.06 MJ and a radius of 1.09−0.05+0.08RJ. Despite having the longest orbital period (P = 2.26 days) of the three planets, TOI-169b receives the most irradiation and is situated on the edge of the Neptune desert. All three host stars are metal rich with Fe / H ranging from 0.18 to0.24.
Oxygen availability in aquatic habitats is a major environmental factor influencing the ecology, behaviour, and physiology of fishes. This study evaluates the contribution of source population and ...hypoxic acclimatization of the African fish, Barbus neumayeri, in determining growth and tissue metabolic enzyme activities. Individuals were collected from two sites differing dramatically in concentration of dissolved oxygen (DO), Rwembaita Swamp (annual average DO 1.35 mgO2 L(-1)) and Inlet Stream West (annual average DO 5.58 mgO2 L(-1)) in Kibale National Park, Uganda, and reciprocally transplanted using a cage experiment in the field, allowing us to maintain individuals under natural conditions of oxygen, food availability, and flow. Fish were maintained under these conditions for four weeks and sampled for growth rate and the activities of phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS), and cytochrome c oxidase (CCO) in four tissues, liver, heart, brain, and skeletal muscle.
Acclimatization to the low DO site resulted in lower growth rates, lower activities of the aerobic enzyme CCO in heart, and higher activities of the glycolytic enzyme PFK in heart and skeletal muscle. The activity of LDH in liver tissue was correlated with site of origin, being higher in fish collected from a hypoxic habitat, regardless of acclimatization treatment.
Our results suggest that the influence of site of origin and hypoxic acclimatization in determining enzyme activity differs among enzymes and tissues, but both factors contribute to higher glycolytic capacity and lower aerobic capacity in B. neumayeri under naturally-occurring conditions of oxygen limitation.
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