bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of post-transcriptional modulators of metalloproteins in response to metal deficiencies
Authors: Perea-García Ana , Puig Sergi , Peñarrubia Lola 
Published: November 2021

AbstractCopper and iron proteins have a wide range of functions in living organisms. Metal assembly into metalloproteins is a complex process, where mismetalation is detrimental and energy consuming to cells. Under metal deficiency, metal distribution is expected to reach a metalation ranking, prioritizing essential versus dispensable metalloproteins, while avoiding interference with other metals and protecting metal-sensitive processes. In this review, we propose that post-transcriptional modulators of metalloprotein mRNA (ModMeR) are good candidates in metal prioritization under metal-limited conditions. ModMeR target high quota or redundant metalloproteins and, by adjusting their synthesis, ModMeR act as internal metal distribution valves. Inappropriate metalation of ModMeR targets could compete with metal delivery to essential metalloproteins and interfere with metal-sensitive processes, such as chloroplastic photosynthesis and mitochondrial respiration. Regulation of ModMeR targets could increase or decrease the metal flow through interconnected pathways in cellular metal distribution, helping to achieve adequate differential metal requirements. Here, we describe and compare ModMeR that function in response to copper and iron deficiencies. Specifically, we describe copper-miRNAs from Arabidopsis thaliana and diverse iron ModMeR from yeast, mammals, and bacteria under copper and iron deficiencies, as well as the influence of oxidative stress. Putative functions derived from their role as ModMeR are also discussed.
Probing cool giants in unresolved galaxies using fluctuation eigenspectra: A demonstration using high-resolution MUSE observations of NGC 5128
Authors: Smith Russell J 
Published: November 2021

ABSTRACT
I describe and demonstrate a new approach to using spectroscopic data to exploit Poisson sampling fluctuations in unresolved stellar populations. The method is introduced using spectra predicted for independent samples of stars from a 10 Gyr population using a simple stochastic spectral synthesis model. A principal components analysis shows that &gt;99 per cent of the spectral variation in the red-optical can be attributed to just three ‘fluctuation eigenspectra’, which can be related to the number of giant stars present in each sample, and their distribution along the isochrone. The first eigenspectrum effectively encodes the spectrum of the coolest giant branch stars, and is equivalent to the ratio between high- and low-flux pixels discussed in previous literature. The second and third eigenspectra carry higher-order information from which the giant-star spectral sequence can in principle be reconstructed. I demonstrate the method in practice using observations of part of NGC 5128, obtained with the MUSE narrow-field adaptive optics mode. The expected first eigenspectrum is easily recovered from the data, and closely matches the model results except for small differences around the Ca ii triplet. The second eigenspectrum is below the noise level of the present observations. A future application of the method would be to the cores of giant ellipticals to probe the spectra of cool giant stars at high metallicity and with element abundance patterns not accessible in the Milky Way.
Velocity structure functions in multiphase turbulence: interpreting kinematics of Hα filaments in cool-core clusters
Authors: Mohapatra Rajsekhar , Jetti Mrinal , Sharma Prateek , Federrath Christoph 
Published: November 2021

ABSTRACT
The central regions of cool-core galaxy clusters harbour multiphase gas, with gas temperatures ranging from $10$ to $10^7\, \mathrm{K}$. Feedback from active galactic nuclei jets prevents the gas from undergoing a catastrophic cooling flow. However, the exact mechanism of this feedback energy input is unknown, mainly due to the lack of velocity measurements of the hot-phase gas. However, recent observations have measured the velocity structure functions (VSFs) of the cooler molecular (${\sim} 10\, \mathrm{K}$) and Hα filaments (${\sim} 10^4\, \mathrm{K}$) and used them to indirectly estimate the motions of the hot phase. In the first part of this study, we conduct high-resolution (3843–15363 resolution elements) simulations of homogeneous isotropic subsonic turbulence, without radiative cooling. We analyse the second-order velocity structure functions (VSF2) in these simulations and study the effects of varying spatial resolution, the introduction of magnetic fields, and the effect of projection along the line of sight (LOS) on it. In the second part of the study, we analyse high-resolution (7683 resolution elements) idealized simulations of multiphase turbulence in the intracluster medium from the companion study Mohapatra et al. We compare the VSF2 for both the hot ($T\sim 10^7\, \mathrm{K}$) and cold ($T\sim 10^4\, \mathrm{K}$) phases and find that their amplitude depends on the density contrast between the phases. They have similar scaling with separation, but introducing magnetic fields steepens the VSF2 of only the cold phase. We also find that projection along the LOS steepens the VSF2 for the hot phase and mostly flattens it for the cold phase.
Secular evolution of MHD wind-driven discs: analytical solutions in the expanded α-framework
Authors: Tabone Benoît , Rosotti Giovanni P , Cridland Alexander J , Armitage Philip J , Lodato Giuseppe 
Published: November 2021

ABSTRACT
The evolution of protoplanetary discs and the related process of planet formation is regulated by angular momentum transport and mass-loss processes. Over the past decade, the paradigm of viscosity has been challenged and MHD disc winds appear as a compelling scenario to account for disc accretion. In this work, we aim to construct the equivalent of the widely used analytical description of viscous evolution for the MHD wind case. The transport of angular momentum and mass induced by the wind is parametrized by an α-like parameter and by the magnetic lever arm parameter λ. Extensions of the paradigmatic Lynden-Bell and Pringle similarity solutions to the wind case are presented. We show that wind-driven accretion leads to a steeper decrease in the disc mass and accretion rate than in viscous models due to the absence of disc spreading. If the decline of the magnetic field strength is slower than that of the gas surface density, the disc is dispersed after a finite time. The evolution of the disc in the $\dot{M}_*-M_{D}$ plane is sensitive to the wind and turbulence parameters. A disc population evolving under the action of winds can exhibit a correlation between $\dot{M}_*$ and MD depending on the initial conditions. The simplified framework proposed in this work opens to a new avenue to test the effectiveness of wind-driven accretion from the observed disc demographics and constitutes an important step to include wind-driven accretion in planet population synthesis models.
The PG-RQS survey. Building the radio spectral distribution of radio-quiet quasars. I. The 45-GHz data
Authors: Baldi R D , Laor A , Behar E , Horesh A , Panessa F , McHardy I , Kimball A 
Published: November 2021

ABSTRACT
The origin of the radio emission in radio-quiet quasars (RQQs) remains unclear. Radio emission may be produced by a scaled-down version of the relativistic jets observed in radio-loud (RL) AGN, an AGN-driven wind, the accretion disc corona, AGN photon-ionization of ambient gas (free–free emission), or star formation (SF). Here, we report a pilot study, part of a radio survey (‘PG-RQS’) aiming at exploring the spectral distributions of the 71 Palomar–Green (PG) RQQs: high angular resolution observations (∼50 mas) at 45 GHz (7 mm) with the Karl G. Jansky Very Large Array of 15 sources. Sub-mJy radio cores are detected in 13 sources on a typical scale of ∼100 pc, which excludes significant contribution from galaxy-scale SF. For 9 sources the 45-GHz luminosity is above the lower frequency (∼1–10 GHz) spectral extrapolation, indicating the emergence of an additional flatter-spectrum compact component at high frequencies. The X-ray luminosity and black hole (BH) mass, correlate more tightly with the 45-GHz luminosity than the 5-GHz. The 45 GHz-based radio-loudness increases with decreasing Eddington ratio and increasing BH mass MBH. These results suggest that the 45-GHz emission from PG RQQs nuclei originates from the innermost region of the core, probably from the accretion disc corona. Increasing contributions to 45-GHz emission from a jet at higher MBH and lower Eddington ratios and from a disc wind at large Eddington ratios are still consistent with our results. Future full radio spectral coverage of the sample will help us investigating the different physical mechanisms in place in RQQ cores.
No evidence for a strong decrease of planetesimal accretion in old white dwarfs
Authors: Blouin Simon , Xu (许偲艺) Siyi 
Published: November 2021

ABSTRACT
A large fraction of white dwarfs are accreting or have recently accreted rocky material from their planetary systems, thereby ‘polluting’ their atmospheres with elements heavier than helium. In recent years, the quest for mechanisms that can deliver planetesimals to the immediate vicinity of their central white dwarfs has stimulated a flurry of modelling efforts. The observed time evolution of the accretion rates of white dwarfs through their multi-Gyr lifetime is a crucial test for dynamical models of evolved planetary systems. Recent studies of cool white dwarf samples have identified a significant decrease of the mass accretion rates of cool, old white dwarfs over Gyr time-scales. Here, we revisit those results using updated white dwarf models and larger samples of old polluted H- and He-atmosphere white dwarfs. We find no compelling evidence for a strong decrease of their time-averaged mass accretion rates for cooling times between 1 and 8 Gyr. Over this period, the mass accretion rates decrease by no more than a factor of the order of 10, which is one order of magnitude smaller than the decay rate found in recent works. Our results require mechanisms that can efficiently and consistently deliver planetesimals inside the Roche radius of white dwarfs over at least 8 Gyr.
Constraining the evolution of cataclysmic variables via the masses and accretion rates of their underlying white dwarfs
Authors: Pala A F , Gänsicke B T , Belloni D , Parsons S G , Marsh T R , Schreiber M R , Breedt E , Knigge C , Sion E M , Szkody P , Townsley D , Bildsten L , Boyd D , Cook M J , De Martino D , Godon P , Kafka S , Kouprianov V , Long K S , Monard B , Myers G , Nelson P , Nogami D , Oksanen A , Pickard R , Poyner G , Reichart D E , Rodriguez Perez D , Shears J , Stubbings R , Toloza O 
Published: November 2021

ABSTRACT
We report on the masses (MWD), effective temperatures ($\rm{T_\mathrm{eff}}$), and secular mean accretion rates ($\langle \dot{M} \rangle$) of 43 cataclysmic variable (CV) white dwarfs, 42 of which were obtained from the combined analysis of their Hubble Space Telescope ultraviolet data with the parallaxes provided by the Early Third Data Release of the Gaia space mission, and one from the white dwarf gravitational redshift. Our results double the number of CV white dwarfs with an accurate mass measurement, bringing the total census to 89 systems. From the study of the mass distribution, we derive $\langle M_\mathrm{WD} \rangle = 0.81^{+0.16}_{-0.20}\, \mathrm{M_\odot }$, in perfect agreement with previous results, and find no evidence of any evolution of the mass with orbital period. Moreover, we identify five systems with MWD &lt; 0.5 M⊙, which are most likely representative of helium-core white dwarfs, showing that these CVs are present in the overall population. We reveal the presence of an anticorrelation between the average accretion rates and the white dwarf masses for the systems below the $2\!-\!3\,$ h period gap. Since $\langle \dot{M} \rangle$ reflects the rate of system angular momentum loss, this correlation suggests the presence of an additional mechanism of angular momentum loss that is more efficient at low white dwarf masses. This is the fundamental concept of the recently proposed empirical prescription of consequential angular momentum loss (eCAML) and our results provide observational support for it, although we also highlight how its current recipe needs to be refined to better reproduce the observed scatter in $\rm{T_\mathrm{eff}}$ and $\langle \dot{M} \rangle$, and the presence of helium-core white dwarfs.
Structure, dynamics, and function of SrnR, a transcription factor for nickel-dependent gene expression
Authors: Mazzei Luca , Musiani Francesco , Żerko Szymon , Koźminski Wiktor , Cianci Michele , Beniamino Ylenia , Ciurli Stefano , Zambelli Barbara 
Published: November 2021

AbstractStreptomyces griseus, a bacterium producing antibacterial drugs and featuring possible application in phytoremediation, expresses two metal-dependent superoxide dismutase (SOD) enzymes, containing either Fe(II) or Ni(II) in their active site. In particular, the alternative expression of the two proteins occurs in a metal-dependent mode, with the Fe(II)-enzyme gene (sodF) repressed at high intracellular Ni(II) concentrations by a two-component system (TCS). This complex involves two proteins, namely SgSrnR and SgSrnQ, which represent the transcriptional regulator and the Ni(II) sensor of the system, respectively. SgSrnR belongs to the ArsR/SmtB family of metal-dependent transcription factors; in the apo-form and in the absence of SgSrnQ, it can bind the DNA operator of sodF, upregulating gene transcription. According to a recently proposed hypothesis, Ni(II) binding to SgSrnQ would promote its interaction with SgSrnR, causing the release of the complex from DNA and the consequent downregulation of the sodF expression. SgSrnQ is predicted to be highly disordered, thus the understanding, at the molecular level, of how the SgSrnR/SgSrnQ TCS specifically responds to Ni(II) requires the knowledge of the structural, dynamic, and functional features of SgSrnR. These were investigated synergistically in this work using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, atomistic molecular dynamics calculations, isothermal titration calorimetry, and in silico molecular docking. The results reveal that the homodimeric apo-SgSrnR binds to its operator in a two-step process that involves the more rigid globular portion of the protein and leaves its largely disordered regions available to possibly interact with the disordered SgSrnQ in a Ni-dependent process.
A simple and general approach to generate photoactivatable DNA processing enzymes
Authors: Kesici Merve-Zeynep , Tinnefeld Philip , Vera Andrés Manuel 
Published: November 2021

Abstract
DNA processing enzymes, such as DNA polymerases and endonucleases, have found many applications in biotechnology, molecular diagnostics, and synthetic biology, among others. The development of enzymes with controllable activity, such as hot-start or light-activatable versions, has boosted their applications and improved the sensitivity and specificity of the existing ones. However, current approaches to produce controllable enzymes are experimentally demanding to develop and case-specific. Here, we introduce a simple and general method to design light-start DNA processing enzymes. In order to prove its versatility, we applied our method to three DNA polymerases commonly used in biotechnology, including the Phi29 (mesophilic), Taq, and Pfu polymerases, and one restriction enzyme. Light-start enzymes showed suppressed polymerase, exonuclease, and endonuclease activity until they were re-activated by an UV pulse. Finally, we applied our enzymes to common molecular biology assays and showed comparable performance to commercial hot-start enzymes.
Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors
Authors: Doz François , van Tilburg Cornelis M , Geoerger Birgit , Højgaard Martin , Øra Ingrid , Boni Valentina , Capra Michael , Chisholm Julia , Chung Hyun Cheol , DuBois Steven G , Gallego-Melcon Soledad , Gerber Nicolas U , Goto Hiroaki , Grilley-Olson Juneko E , Hansford Jordan R , Hong David S , Italiano Antoine , Kang Hyoung Jin , Nysom Karsten , Thorwarth Anne , Stefanowicz Joanna , Tahara Makoto , Ziegler David S , Gavrilovic Igor T , Norenberg Ricarda , Dima Laura , De La Cuesta Esther , Laetsch Theodore W , Drilon Alexander , Perreault Sebastien 
Published: November 2021

AbstractBackgroundLarotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.MethodsPatients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR).ResultsAs of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. The 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3–4 in 3 patients. No new safety signals were identified.ConclusionsIn patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.
The Ethics of Selective Mandatory Vaccination for COVID-19
Authors: Williams Bridget M 
Published: November 2021

Abstract
With evidence of vaccine hesitancy in several jurisdictions, the option of making COVID-19 vaccination mandatory requires consideration. In this paper I argue that it would be ethical to make the COVID-19 vaccination mandatory for older people who are at highest risk of severe disease, but if this were to occur, and while there is limited knowledge of the disease and vaccines, there are not likely to be sufficient grounds to mandate vaccination for those at lower risk. Mandating vaccination for those at high risk of severe disease is justified on the basis of the harm principle, as there is evidence that this would remove the grave public health threat of COVID-19. The risk–benefit profile of vaccination is also more clearly in the interests of those at highest risk, so mandatory vaccination entails a less severe cost to them. Therefore, a selective mandate would create fairness in the distribution of risks. The level of coercion imposed by a mandate would need to be proportionate, and it is likely that multiple approaches will be needed to increase vaccine uptake. However, a selective mandate for COVID-19 vaccines is likely to be an ethical choice and should be considered by policy-makers.
Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis
Authors: De Craemer Ann-Sophie , Renson Thomas , Deroo Liselotte , Van Praet Liesbet , Cypers Heleen , Varkas Gaëlle , Joos Rik , Devinck Mieke , Gyselbrecht Lieve , Peene Isabelle , Thevissen Kristof , Costantino Félicie , D’Agostino Maria-Antonietta , Lenaerts Jan , Carron Philippe , Van den Bosch Filip , Elewaut Dirk 
Published: November 2021

Abstract

Objectives
To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant).

Methods
Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis.

Results
From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time (‘High’), the other rapidly evolving to low disease activity (‘Low’). In cluster A patients, peripheral manifestations predisposed to the ‘High’ trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR)  = 2.1, 95% CI: 1.0, 4.4, P = 0.04 – Cox proportional-hazards model).

Conclusion
Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.
How Important Is Temptation Spending? Maybe Less than We Thought
Authors: Brune Lasse , Kerwin Jason T , Li Qingxiao 
Published: November 2021

Abstract
Temptation plays a key role in theoretical work on spending and saving in developing countries. The limited empirical evidence on its importance, however, suggests that cash transfers do not induce increases in temptation spending. This paper expands the evidence base by studying the effect of randomized exposure to temptation on spending decisions in rural Malawi. Consistent with the cash transfer literature, a more tempting environment does not induce significant changes in temptation spending. However, the magnitudes of both temptation spending levels and the treatment effects are somewhat sensitive to the definition of temptation spending used. This paper examines the potential factors that may be driving these null results, and suggests that future research may find a limited role for temptation in the economic decisions of the poor.