bluuebunny/crossref_metadata_2025 huggingface dataset:
Galaxy lens reconstruction based on strongly lensed gravitational waves: similarity transformation degeneracy and mass-sheet degeneracy
Authors: Poon Jason S C , Rinaldi Stefano , Janquart Justin , Narola Harsh , Hannuksela Otto A
Published: December 2024

Gravitational wave (GW) galaxy lens reconstruction is a crucial step for many GW lensing science applications. However, dark siren GW lensing without observed electromagnetic (EM) counterpart suffers from similarity transformation and mass-sheet degeneracy. We review these two degeneracies and discuss their implications on GW-based lens reconstruction and two well-known GW lensing science cases: Hubble constant measurement and testing modified GW propagation. Building upon previous works, our conclusions are (1) GWs can only infer the scale-free lens model parameters, dimensionless source position, GW luminosity distance and time-delay scaling (a combination of Einstein radius, redshifts, and cosmology). (2) Lens reconstruction (of singular isothermal ellipsoid lens) with only two GW signals is unlikely to yield a complete lens model, while four (three) signals can measure all the above parameters accurately (with large uncertainties). (3) The similarity transformation degeneracy causes the redshifts/Einstein radius/cosmology to be degenerate in dark siren measurements. Breaking the degeneracy can be achieved by supplementing the GWs with EM observation of lens redshifts/Einstein radius (source redshift is not required). (4) The mass-sheet degeneracy causes the GW luminosity distance to be degenerate with a constant mass sheet. (5) Contrary to expectation, the Hubble constant is degenerate with the mass-sheet even when supplemented with EM counterpart and can only be lifted with lens galaxy velocity dispersion measurement, while modified GW propagation test is unaffected. These properties highlight the need for GW observations to be supplemented by EM observations, which could become accessible through a lens archival search or a rapid EM follow-up.
No evidence for fast, galaxy-wide ionized outflows in a nearby quasar – the importance of accounting for beam smearing
Authors: Holden Luke R , Tadhunter Clive N
Published: December 2024

To test the scenario that outflows accelerated by active galactic nuclei (AGN) have a major impact on galaxy-wide scales, we have analysed deep Very Large Telescope/Multi Unit Spectroscopic Explorer (VLT/MUSE) data for the type-2 quasar/ultraluminous infrared galaxy F13451+1232 – an object that represents the major mergers considered in some models of galaxy evolution. After carefully accounting for the effects of atmospheric seeing that had smeared the emission from known compact nuclear outflows across the MUSE field of view, we find that the large-scale kinematics in F13451+1232 are consistent with gravitational motions that are expected in a galaxy merger. Therefore, the fast ($\mathrm{W_{80}}\gt 500$ km s$^{-1}$) warm-ionized AGN-driven outflows in this object are limited to the central $\sim$100 pc of the galaxy, although we cannot rule out larger scale, lower velocity outflows. Moreover, we directly demonstrate that failure to account for the beam-smearing effects of atmospheric seeing would have led to the mass outflow rates and kinetic powers of spatially extended emission being overestimated by orders of magnitude. We also show that beam-smeared compact-outflow emission can be significant beyond radial distances of 3.5 arcsec (more than 8 times the radius of the seeing disc), and support the argument that some previous claims of large-scale outflows in active galaxies were likely the result of this effect rather than genuine galaxy-wide ($r\gt 5$ kpc) outflows. Our study therefore provides further evidence that warm-ionized AGN-driven outflows are limited to the central kiloparsecs of galaxies and highlights the critical importance of accounting for atmospheric seeing in ground-based observational studies of active galaxies.
The spectral behaviour and variability of narrow-line Seyfert 1 galaxies with Australia Telescope Compact Array observations
Authors: Shao Xi , Edwards Philip G , Stevens Jamie , Gu Minfeng , Galvin Timothy J , Huynh Minh T
Published: December 2024

We present multifrequency radio data for a sample of Narrow-Line type 1 Seyfert (NLS1) galaxies. We first focus on the sub-class of gamma-ray emitting NLS1 galaxies, studying the long-term radio variability of five sources and comparing it to their gamma-ray state. We then extend the observations of the southern NLS1 galaxy sample of Chen et al. by observing several candidate NLS1 sources for the first time, and re-observing several other gamma-ray-quiet sources to obtain a first indication of their radio variability. We find that the gamma-ray emitting NLS1 galaxies are highly variable radio emitters and that there are instances of contemporaneous flaring activity between the radio and gamma-ray bands (PKS 0440$-$00, PMN J0948+0022, and PKS 1244$-$255). However, there are also cases of significant radio outbursts without gamma-ray counterparts (PMN J0948+0022 and PKS 2004$-$447). The five gamma-ray NLS1s favour flat or inverted radio spectra, although the spectral indices vary significantly over time. For the gamma-ray-quiet sample, the difference between the previous observations at 5.5 GHz and new Australia Telescope Compact Array (ATCA) observations indicates that over half of the 14 sources exhibit apparent variability. In contrast to gamma-ray-loud sources, gamma-ray-quiet objects tend to have steep spectra, especially in the lower radio band (887.5–1367.5 MHz) of Australian Square Kilometre Array Pathfinder (ASKAP) data, with a number of the variable sources having flatter spectra at higher radio frequencies.
Comparing E-MOSAICS predictions of high-redshift proto-globular clusters with JWST observations in lensed galaxies
Authors: Pfeffer Joel , Forbes Duncan A , Romanowsky Aaron J , Bastian Nate , Crain Robert A , Kruijssen J M Diederik , Bekki Kenji , Brodie Jean P , Chevance Mélanie , Couch Warrick J , Gannon Jonah S
Published: December 2024

High-resolution imaging and strong gravitational lensing of high-redshift galaxies have enabled the detection of compact sources with properties similar to nearby massive star clusters. Often found to be very young, these sources may be globular clusters detected in their earliest stages. In this work, we compare predictions of high-redshift ($z \sim 1$–10) star cluster properties from the E-MOSAICS simulation of galaxy and star cluster formation with those of the star cluster candidates in strongly lensed galaxies from JWST and Hubble Space Telescope (HST) imaging. We select galaxies in the simulation that match the luminosities of the majority of lensed galaxies with star cluster candidates observed with JWST. We find that the luminosities, ages, and masses of the brightest star cluster candidates in the high-redshift galaxies are consistent with the E-MOSAICS model. In particular, the brightest cluster ages are in excellent agreement. The results suggest that star clusters in both low- and high-redshift galaxies may form via common mechanisms. However, the brightest clusters in the lensed galaxies tend to be $\approx 1$–$1.5 \, \rm {mag}$ brighter and $\approx 0.5$ dex more massive than the median E-MOSAICS predictions. We discuss the large number of effects that could explain the discrepancy, including simulation and observational limitations, stellar population models, cluster detection biases, and nuclear star clusters. Understanding these limitations would enable stronger tests of globular cluster formation models.
Stage IV baryonic feedback correction for non-Gaussianity inference
Authors: Grandón Daniela , Sellentin Elena
Published: December 2024

Non-Gaussian statistics of the projected weak lensing field are powerful estimators that can outperform the constraining power of the two-point functions in inferring cosmological parameters. This is because these estimators extract the non-Gaussian information contained in the small scales. However, fully leveraging the statistical precision of such estimators is hampered by theoretical uncertainties, such as those arising from baryonic physics. Moreover, as non-Gaussian estimators mix different scales, there exists no natural cut-off scale below which baryonic feedback can be completely removed. We therefore present a Bayesian solution for accounting for baryonic feedback uncertainty in weak lensing non-Gaussianity inference. Our solution implements Bayesian model averaging (BMA), a statistical framework that accounts for model uncertainty and combines the strengths of different models to produce more robust and reliable parameter inferences. We demonstrate the effectiveness of this approach in a Stage IV convergence peak count analysis, including three baryonic feedback models. We find that the resulting BMA posterior distribution safeguards parameter inference against biases due to baryonic feedback, and therefore provides a robust framework for obtaining accurate cosmological constraints at Stage IV precision under model uncertainty scenarios.
JADES: measuring reionization properties using Lyman-alpha emission
Authors: Jones Gareth C , Bunker Andrew J , Saxena Aayush , Arribas Santiago , Bhatawdekar Rachana , Boyett Kristan , Cameron Alex J , Carniani Stefano , Charlot Stephane , Curtis-Lake Emma , Hainline Kevin , Johnson Benjamin D , Kumari Nimisha , Maseda Michael V , Rix Hans-Walter , Robertson Brant E , Tacchella Sandro , Übler Hannah , Williams Christina C , Willott Chris , Witstok Joris , Zhu Yongda
Published: December 2024

Ly$\alpha$ is the transition to the ground state from the first excited state of hydrogen (the most common element). Resonant scattering of this line by neutral hydrogen greatly impedes its emergence from galaxies, so the fraction of galaxies emitting Ly$\alpha$ is a tracer of the neutral fraction of the intergalactic medium (IGM), and thus the history of reionization. In previous works, we used early JWST/NIRSpec data from the JWST Advanced Deep Extragalactic Survey (JADES) to classify and characterize Ly$\alpha$ emitting galaxies (LAEs). This survey is approaching completion, and the current sample is nearly an order of magnitude larger. From a sample of 795  galaxies in JADES at $4.0\lt z\lt 14.3$, we find evidence for Ly$\alpha$ emission in 150 sources. We reproduce the previously found correlation between Ly$\alpha$ escape fraction ($f\rm _{esc}^{Ly\alpha }$) – Ly$\alpha$ rest-frame equivalent width (${\rm REW}_{\rm Ly\alpha }$) and the negative correlation between Ly$\alpha$ velocity offset – $f\rm _{esc}^{Ly\alpha }$. Both $f\rm _{esc}^{Ly\alpha }$ and ${\rm REW}_{\rm Ly\alpha }$ decrease with redshift ($z\gtrsim 5.5$), indicating the progression of reionization on a population scale. Our data are used to demonstrate an increasing IGM transmission of Ly$\alpha$ from $z\sim 14-6$. We measure the completeness-corrected fraction of LAEs ($X\rm _{Ly\alpha }$) from $z=4-9.5$. An application of these $X\rm _{Ly\alpha }$ values to the results of previously utilized semi-analytical models suggests a high neutral fraction at $z=7$ (${X_{\rm HI}}\sim 0.8-0.9$). Using an updated fit to the intrinsic distribution of ${\rm REW}_{\rm Ly\alpha }$ results in a lower value in agreement with current works (${X_{\rm HI}}= 0.64_{-0.21}^{+0.13}$). This sample of LAEs will be paramount for unbiased population studies of galaxies in the EoR.
Investigating the correlation between the magnetic field orientation and molecular outflow direction in some molecular clouds
Authors: Nath Mazumdar S , Das H S , Wolf S
Published: December 2024

This study examines the relationship between the magnetic field orientation of a molecular cloud and its outflow axis, using data from 22 molecular clouds. We find that the position angles of the outflow axis ($\theta _{\text{out}}$) and the cloud-scale magnetic field in the core, measured in the submillimetre region ($\theta _B^{\text{sub}}$), are correlated to each other irrespective of the alignment or misalignment between the two axes. However, it is important to note that these observed position angles are projections on to the plane of the sky. To assess the statistical significance of our findings, we conduct a statistical test to account for the projection effect and find minimal impact. Moreover, we identify a possible role of the Galactic magnetic field orientation ($\theta _{\text{GP}}$) in determining the outflow direction by assessing the offset ($\theta _{\text{off}} = \theta _B - \theta _{\text{GP}}$) in both the core and envelope regions. Furthermore, we explore the influence of parameters such as magnetic field strength (B), the position angle of the minor axis of the cloud cores ($\theta _{\text{min}}$), the inclination angle of the outflow ($i_{\text{out}}$), and other factors on the alignment between the outflow and cloud-scale magnetic field axes ($|\theta _{\text{OB}}| = |\theta _{\text{out}} - \theta _B^{\text{sub}}|$). Our analysis suggests that the orientation of the outflow axis is determined by the combined influence of the magnetic field orientation, the minor axis, the inclination angle of the outflow, and the associated magnetic field strength.
Broad-band study of the Be X-ray binary RX J0520.5–6932 during its outburst in 2024
Authors: Yang H N , Maitra C , Vasilopoulos G , Haberl F , Jenke P A , Karaferias A S , Sharma R , Beri A , Ji L , Jin C , Yuan W , Zhang Y J , Wang C Y , Xu X P , Liu Y , Zhang W D , Zhang C , Ling Z X , Liu H Y , Cheng H Q , Pan H W
Published: December 2024

A new giant outburst of the Be X-ray binary RX J0520.5–6932 was detected and subsequently observed with several space-borne and ground-based instruments. This study presents a comprehensive analysis of the optical and X-ray data, focusing on the spectral and timing characteristics of selected X-ray observations. A joint fit of spectra from simultaneous observations performed by the X-ray telescope (XRT) on the Neil Gehrels Swift Observatory (Swift) and Nuclear Spectroscopic Telescope ARray (NuSTAR) provides broad-band parameter constraints, including a cyclotron resonant scattering feature (CRSF) at $32.2_{-0.7}^{+0.8}$ keV with no significant energy change since 2014, and a weaker Fe line. Independent spectral analyses of observations by the Lobster Eye Imager for Astronomy, Einstein Probe (EP), Swift–XRT, and NuSTAR demonstrate the consistency of parameters across different bands. Luminosity variations during the current outburst were tracked. The light curve of the Optical Gravitational Lensing Experiment (OGLE) aligns with the X-ray data in both 2014 and 2024. Spin evolution over 10 yr is studied after adding Fermi Gamma-ray Burst Monitor data, improving the orbital parameters, with an estimated orbital period of 24.39 d, slightly differing from OGLE data. Despite intrinsic spin-up during outbursts, a spin-down of $\sim$0.04 s over 10.3 yr is suggested. For the new outburst, the pulse profiles indicate a complicated energy-dependent shape, with decreases around 15 and 25 keV in the pulsed fraction, a first for an extragalactic source. Phase-resolved NuSTAR data indicate variations in parameters such as flux, photon index, and CRSF energy with rotation phase.
Ejecta width and magnetization reflected in gamma-ray burst early afterglows: implication for reverse shock component and shallow decay phase
Authors: Kusafuka Yo , Asano Katsuaki
Published: December 2024

To study the ejecta property dependence of the gamma-ray burst (GRB) afterglow, we carry out spherically symmetrical one-dimensional special relativistic magnetohydrodynamic simulations of magnetized outflows with an adaptive mesh refinement method. The Lorentz factor evolutions of forward and reverse shocks induced by the interaction between magnetized ejecta and an ambient medium are investigated for a wide range of magnetization and width of the ejecta. The forward shock evolution is described by the magnetic acceleration, coasting, transition, and self-similar deceleration phases. According to our simulation results, we numerically calculate the corresponding radiation. Based on our numerical results, to model afterglow light curves in general cases, we construct semi-analytical formulae for the Lorentz factor evolutions. The magnetization and ejecta width dependence are clearly seen in the reverse shock light curves. The transition phase with a reasonable ejecta width can reproduce the shallow decay phase in the observed GRB afterglow. The inverse Compton emission in the magnetic acceleration phase can be responsible for the very steep rise of the early TeV emission in GRB 221009A.
Building a Semi-analytic Black Hole Seeding Model using IllustrisTNG Host Galaxies
Authors: Evans Analis Eolyn , Blecha Laura , Bhowmick Aklant Kumar
Published: December 2024

A major open question in astrophysics is the mechanisms by which massive black holes (BHs) form in the early Universe, which pose constraints on seeding models. We study BH formation and evolution in a flexible model combining the cosmological IllustrisTNG (TNG) simulations with semi-analytic modelling in post-processing. We identify our TNG model hosts based on various criteria including a minimum gas mass of $10^7$–$10^9$${\rm M}_{\odot }$, total host mass of $10^{8.5}$–$10^{10.5}$${\rm M}_{\odot }$, and a maximum gas metallicity of 0.01–0.1 $\mathrm{Z}_{\odot }$. Each potential host is assigned a BH seed with a probability of 0.01–1. The populations follow the TNG galaxy merger tree. This approach improves upon the predictive power of the simple TNG BH seeding prescription, narrowing down plausible seeding parameter spaces, and it is readily adaptable to other cosmological simulations. Several model realizations predict $z\lesssim 4$ BH mass densities that are consistent with empirical data as well as the TNG BHs. However, high-redshift BH number densities can differ by factors of $\sim$ 10 to $\gtrsim$ 100 between seeding parameters. In most model realizations, $\lesssim 10^5$${\rm M}_{\odot }$ BHs substantially outnumber heavier BHs at high redshifts. Mergers between such BHs are prime targets for gravitational-wave detection with Laser Interferometer Space Antenna. The $z=0$ BH mass densities in most realizations of the model agree well with observations, but our strictest seeding criteria fail at high redshift. Our findings strongly motivate the need for better empirical constraints on high-z BHs, and they underscore the significance of recent active galactic nucleus discoveries with JWST.
First investigation of void statistics in numerical relativity simulations
Authors: Williams Michael J , Macpherson Hayley J , Wiltshire David L , Stevens Chris
Published: December 2024

We apply and extend standard tools for void statistics to cosmological simulations that solve Einstein’s equations with numerical relativity (NR). We obtain a simulated void catalogue without Newtonian approximations, using a new watershed void finder that operates on fluid-based NR simulations produced with the Einstein Toolkit. We compare and contrast measures of void size and void fraction, and compare radial stacked density profiles to empirically-derived Hamaus–Sutter–Wandelt (HSW) density profiles and profiles based on distance to void boundaries. We recover statistics roughly consistent with Newtonian N-body simulations where such a comparison is meaningful. We study the variation of dynamical spatial curvature and local expansion explicitly demonstrating the spatial fluctuations of these quantities in void regions. We find that voids in our simulations expand ∼10–30 per cent faster than the global average, and the spatial curvature density parameter in the centre of voids reaches ∼60–80 per cent.
Neural network emulator to constrain the high-z IGM thermal state from Lyman-α forest flux autocorrelation function
Authors: Jin Zhenyu , Wolfson Molly , Hennawi Joseph F , González-Hernández Diego
Published: December 2024

We present a neural network emulator to constrain the thermal parameters of the intergalactic medium (IGM) at $5.4 \le z \le 6.0$ using the Lyman-$\alpha$ (Ly $\alpha$) forest flux autocorrelation function. Our autodifferentiable JAX-based framework accelerates the surrogate model generation process using approximately 100 sparsely sampled Nyx hydrodynamical simulations with varying combinations of thermal parameters, i.e. the temperature at mean density $T_0$, the slope of the temperature–density relation $\gamma$, and the mean transmission flux $\langle F \rangle$. We show that this emulator has a typical accuracy of 1.0 per cent across the specified redshift range. Bayesian inference of the IGM thermal parameters, incorporating emulator uncertainty propagation, is further expedited using NumPyro Hamiltonian Monte Carlo. We compare both the inference results and computational cost of our framework with the traditional nearest-neighbour interpolation approach applied to the same set of mock Ly $\alpha$ flux. By examining the credibility contours of the marginalized posteriors for $T_0, \gamma , \text{and}~\langle F \rangle$ obtained using the emulator, the statistical reliability of measurements is established through inference on 100 realistic mock data sets of the autocorrelation function.
Statistical dependence of ion-scale waves’ spacecraft-frame polarization observed by Parker Solar Probe on local proton and alpha non-Maxwellian features
Authors: Liu Wen , Jia Huan-Yu , Liu Si-Ming
Published: December 2024

This paper statistically investigate the relationship between the polarization of ion-scale waves in the spacecraft frame and the background plasma environment based on parker solar probe observations within 0.3 au. Our statistical results show that the background solar wind environment of left-handed (LH) and right-handed (RH) ion-scale waves in the spacecraft frame is significantly different. The LH waves corresponds to higher ion temperature ($T_\mathrm{ p}\sim 45.16$ eV, $T_{\alpha }\sim 327.63$ eV), larger alpha particle density ratio ($N_{\alpha }/N_\mathrm{ p}\sim 0.016$), larger temperature ratio ($T_{\alpha }/T_\mathrm{ p}\sim 7.20$), and larger differential speed ($(V_{\alpha }-V_\mathrm{ p})/V_\mathrm{ A}\sim 0.395$) than those ($T_\mathrm{ p}\sim 18.38$ eV, $T_{\alpha }\sim 77.25$ eV, $N_{\alpha }/N_\mathrm{ p}\sim 0.007$, $T_{\alpha }/T_\mathrm{ p}\sim 4.22$, $(V_{\alpha }-V_\mathrm{ p})/V_\mathrm{ A}\sim 0.093$) of RH waves. In addition, LH waves mainly corresponds to $V_{\alpha \mathrm{ p}}/V_\mathrm{ A}\gt 0$ (the moment of alpha velocity is larger than the moment of proton velocity) and their occurrence rate of LH ion-scale waves is proportional to $T_{\alpha }$, $T_\mathrm{ p}$, $T_{\alpha }/T_\mathrm{ p}$, $T_{\alpha \parallel }/T_{\mathrm{ p} \parallel }$, and $V_{\alpha \mathrm{ p}}/V_\mathrm{ A}$, while RH waves do the opposite. Moreover, when $T_{\alpha }/T_\mathrm{ p}\gt 10$, only LH ion-scale wave exists and its occurrence rate is high. Besides, our theoretical results suggest that the high occurrence rate regions of spacecraft-frame LH (RH) ion-scale waves seem to prefer generating LH Alfvén/ion cyclotron waves (RH fast magnetosonic/whistler waves).
Asymmetrical Evolution of Promoter Methylation of Mammalian Genes after Duplication
Authors: de la Fuente Mercedes , Mendizabal Isabel , Han Mira V , Yi Soojin V , Alvarez-Ponce David
Published: December 2024

Even though gene duplication is a key source of new genes and evolutionary innovation, it is unclear how duplicates survive the period immediately following gene duplication, in which both copies are functionally redundant. In the absence of epigenetic silencing, the abundance of the gene product would double after gene duplication, which would often have deleterious effects. However, recent duplicates exhibit low expression levels, which could be at least partially explained by high levels of promoter methylation. What evolutionary paths lead to duplicate hypermethylation, and does it affect both duplicates or only one? Here, we compare levels of promoter methylation in 10 human and 16 mouse tissues, between singletons and duplicates and among human–mouse orthologs of different kinds (one-to-one, one-to-many, many-to-one, and many-to-many). Our results indicate that: (i) on average, duplicates are more methylated than singletons in mouse, but less methylated than singletons in human, (ii) recently duplicated genes tend to exhibit high levels of promoter methylation, (iii) genes that undergo duplication tend to be highly methylated before duplication, (iv) after gene duplication, one of the copies (the daughter copy, i.e. the one that relocates to a new genomic context) tends to undergo an additional increase in promoter methylation, whereas the other (the parental copy, which remains in the original genomic location) tends to retain preduplication methylation levels, and (v) daughter copies tend to be lowly expressed. These observations support a model in which daughter copies are repressed via promoter hypermethylation and can thus survive the filter of purifying selection until both copies diverge functionally.
A Spectrum of Audiences for Music Theory, and Some Ways to Connect with Them
Authors: Krebs Harald
Published: December 2024

My paper describes the audiences that I have addressed in public-facing situations—a variety of community audiences, and of academic audiences outside of music. I summarize the tools and techniques that I have found to be useful for connecting with these audiences: visual aids in the form of PowerPoint slides; collaborative creative activity; humor; and live performance.
MirGeneDB 3.0: improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families and updated covariance models
Authors: Clarke Alexander W , Høye Eirik , Hembrom Anju Angelina , Paynter Vanessa Molin , Vinther Jakob , Wyrożemski Łukasz , Biryukova Inna , Formaggioni Alessandro , Ovchinnikov Vladimir , Herlyn Holger , Pierce Alexandra , Wu Charles , Aslanzadeh Morteza , Cheneby Jeanne , Martinez Pedro , Friedländer Marc R , Hovig Eivind , Hackenberg Michael , Umu Sinan Uğur , Johansen Morten , Peterson Kevin J , Fromm Bastian
Published: December 2024

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species. MirGeneDB now contains entries for 21 822 microRNA genes (5160 of these from the new species) belonging to 1743 microRNA families. The inclusion of these new species allowed us to refine both the evolutionary node of appearance of a number of microRNA genes/families, as well as MirGeneDB’s phylogenetically informed nomenclature system. Updated covariance models of all microRNA families, along with all smallRNA read data are now downloadable. These enhanced annotations will allow researchers to analyze microRNA properties such as secondary structure and features of their biogenesis within a robust phylogenetic context and without the database plagued with numerous false positives and false negatives. In light of these improvements, MirGeneDB 3.0 will assume the responsibility for naming conserved novel metazoan microRNAs. MirGeneDB is part of RNAcentral and Elixir Norway and is publicly and freely available at mirgenedb.org.
Distinct interactomes of ADAR1 nuclear and cytoplasmic protein isoforms and their responses to interferon induction
Authors: Vukić Dragana , Cherian Anna , Keskitalo Salla , Bong Yih Tyng , Marônek Martin , Yadav Leena , Keegan Liam P , Varjosalo Markku , O’Connell Mary A
Published: December 2024

The RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is essential for correct functioning of innate immune responses. The ADAR1p110 isoform is mainly nuclear and ADAR1p150, which is interferon (IFN) inducible, is predominately cytoplasmic. Using three different methods – co-immunoprecipitation (co-IP) of endogenous ADAR1, Strep-tag co-IP and BioID with individual ADAR1 isoforms – a comprehensive interactome was generated during both homeostasis and the IFN response. Both known and novel interactors as well as editing regulators were identified. Nuclear proteins were detected as stable interactors with both ADAR1 isoforms. In contrast, BioID identified distinct protein networks for each ADAR1 isoform, with nuclear components observed with ADAR1p110 and components of cytoplasmic cellular condensates with ADAR1p150. RNase A digestion distinguished between distal and proximal interactors, as did a double-stranded RNA (dsRNA)-binding mutant of ADAR1 which demonstrated the importance of dsRNA binding for ADAR1 interactions. IFN treatment did not affect the core ADAR1 interactomes but resulted in novel interactions, the majority of which are proximal interactions retained after RNase A treatment. Short treatment with high molecular weight poly(I:C) during the IFN response resulted in dsRNA-binding-dependent changes in the proximal protein network of ADAR1p110 and association of the ADAR1p150 proximal protein network with some components of antiviral stress granules.
Molecular basis for thiocarboxylation and release of Urm1 by its E1-activating enzyme Uba4
Authors: Sokołowski Mikołaj , Kwasna Dominika , Ravichandran Keerthiraju E , Eggers Cristian , Krutyhołowa Rościsław , Kaczmarczyk Magdalena , Skupien-Rabian Bozena , Jaciuk Marcin , Walczak Marta , Dahate Priyanka , Pabis Marta , Jemioła-Rzemińska Małgorzata , Jankowska Urszula , Leidel Sebastian A , Glatt Sebastian
Published: December 2024

Ubiquitin-related modifier 1 (Urm1) is a highly conserved member of the ubiquitin-like (UBL) family of proteins. Urm1 is a key component of the eukaryotic transfer RNA (tRNA) thiolation cascade, responsible for introducing sulfur at wobble uridine (U34) in several eukaryotic tRNAs. Urm1 must be thiocarboxylated (Urm1-SH) by its E1 activating enzyme UBL protein activator 4 (Uba4). Uba4 first adenylates and then thiocarboxylates the C-terminus of Urm1 using its adenyl-transferase (AD) and rhodanese (RHD) domains. However, the detailed mechanisms of Uba4, the interplay between the two domains, and the release of Urm1 remain elusive. Here, we report a cryo-EM-based structural model of the Uba4/Urm1 complex that reveals the position of its RHD domains after Urm1 binding, and by analyzing the in vitro and in vivo consequence of mutations at the interface, we show its importance for the thiocarboxylation of Urm1. Our results confirm that the formation of the Uba4-Urm1 thioester and thiocarboxylation of Urm1’s C-terminus depend on conserved cysteine residues of Uba4 and that the complex avoids unwanted side-reactions of the adenylate by forming a thioester intermediate. We show how the Urm1-SH product can be released and how Urm1 interacts with upstream (Tum1) and downstream (Ncs6) components of the pathway. Our work provides a detailed mechanistic description of the reaction steps that are needed to produce Urm1-SH, which is required to thiolate tRNAs and persulfidate proteins.
Adaptive immunity of type VI CRISPR-Cas systems associated with reverse transcriptase–Cas1 fusion proteins
Authors: Molina-Sánchez María Dolores , Martínez-Abarca Francisco , Millán Vicenta , Mestre Mario Rodríguez , Stehantsev Pavlo , Stetsenko Artem , Guskov Albert , Toro Nicolás
Published: December 2024

Cas13-containing type VI CRISPR-Cas systems specifically target RNA; however, the mechanism of spacer acquisition remains unclear. We have previously reported the association of reverse transcriptase–Cas1 (RT–Cas1) fusion proteins with certain types of VI-A systems. Here, we show that RT–Cas1 fusion proteins are also recruited by type VI-B systems in bacteria from gut microbiomes, constituting a VI-B1 variant system that includes a CorA-encoding locus in addition to the CRISPR array and the RT–Cas1/Cas2 adaptation module. We found that type VI RT-CRISPR systems were functional for spacer acquisition, CRISPR array processing and interference activity, demonstrating that adaptive immunity mediated by these systems can function independently of other in trans systems. We provide evidence that the RT associated with these systems enables spacer acquisition from RNA molecules. We also found that CorA encoded by type VI-B1 RT-associated systems can transport divalent metal ions and downregulate Cas13b-mediated RNA interference. These findings highlight the importance of RTs in RNA-targeting CRISPR-Cas systems, potentially enabling the integration of RNA-derived spacers into CRISPR arrays as a mechanism against RNA-based invaders in specific environments.
RPA and Rad27 limit templated and inverted insertions at DNA breaks
Authors: Yu Yang , Wang Xin , Fox Jordan , Li Qian , Yu Yang , Hastings P J , Chen Kaifu , Ira Grzegorz
Published: December 2024

Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ∼5–34 bp), templated inverted duplications at DSBs. They are generated through a foldback mechanism that utilizes microhomologies adjacent to the DSB. Enzymatic requirements suggest a hybrid mechanism wherein one end requires Polδ-mediated synthesis while the other end is captured by nonhomologous end joining (NHEJ) or by alternative end joining (Alt-EJ). This process is exacerbated in mutants with low levels or mutated RPA (rtt105Δ; rfa1-t33) or extensive resection deficiency (sgs1Δ exo1Δ). Templated insertions from various distant genomic locations also increase in RPA mutants as well as in rad27Δ and originate from fragile regions of the genome. Among complex insertions, common events are insertions of two sequences, originating from the same locus and with inverted orientation. We propose that these inversions are also formed by microhomology-mediated template switching. Together, we propose that a shortage of RPA, typical in cancer cells, may be a factor that stimulates the formation of templated insertions.
Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis
Authors: Korenfeld Noga , Charni-Natan Meital , Bruse Justine , Goldberg Dana , Marciano-Anaki Dorin , Rotaro Dan , Gorbonos Tali , Radushkevitz-Frishman Talia , Polizzi Arnaud , Nasereddin Abed , Gover Ofer , Bar-Shimon Meirav , Fougerat Anne , Guillou Hervé , Goldstein Ido
Published: December 2024

Mammals withstand frequent and prolonged fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this generates effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’ (i.e. induced more strongly by fasting following ADF). Liver enhancers regulating these genes are also sensitized and harbor increased binding of PPARα, the main ketogenic transcription factor. ADF leads to augmented ketogenesis compared to a single fasting bout in wild-type, but not hepatocyte-specific PPARα-deficient mice. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augment ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated signals.
Spatial regulation of NSUN2-mediated tRNA m5C installation in cognitive function
Authors: Gonskikh Yulia , Tirrito Christian , Bommisetti Praneeth , Mendoza-Figueroa Maria Saraí , Stoute Julian , Kim Joshua , Wang Qin , Song Yuanquan , Liu Kathy Fange
Published: December 2024

Enzyme-mediated modifications of tRNA, such as 5-methylcytosine (m5C) installed by nuclear-enriched NOP2/Sun RNA methyltransferase 2 (NSUN2), play a critical role in neuronal development and function. However, our understanding of these modifications' spatial installation and biological functions remains incomplete. In this study, we demonstrate that a nucleoplasm-localized G679R NSUN2 mutant, linked to intellectual disability, diminishes NSUN2-mediated tRNA m5C in human cell lines and Drosophila. Our findings indicate that inability of G679R-NSUN2 to install m5C is primarily attributed to its reduced binding to tRNA rather than its nucleoplasmic localization. Conversely, an NSUN2 variant lacking an internal intrinsically disordered region (ΔIDR-NSUN2) can install ∼80% m5C within the nucleoplasm. Furthermore, we show that tRNA m5C levels are positively correlated to cognitive performance in Drosophila, where expressing G679R-NSUN2 leads to the most severe social behavioral deficits while expressing ΔIDR-NSUN2 results in less pronounced deficits. This work illuminates the molecular mechanism underlying G679R disease mutation in cognitive function and offers valuable insights into the significance of the cellular localization of m5C installation on tRNA for neuronal function.
When repetita no-longer iuvant: somatic instability of the CAG triplet in Huntington’s disease
Authors: Cattaneo Elena , Scalzo Davide , Zobel Martina , Iennaco Raffaele , Maffezzini Camilla , Besusso Dario , Maestri Simone
Published: December 2024

Trinucleotide repeats in DNA exhibit a dual nature due to their inherent instability. While their rapid expansion can diversify gene expression during evolution, exceeding a certain threshold can lead to diseases such as Huntington’s disease (HD), a neurodegenerative condition, triggered by >36 C–A–G repeats in exon 1 of the Huntingtin gene. Notably, the discovery of somatic instability (SI) of the tract allows these mutations, inherited from an affected parent, to further expand throughout the patient’s lifetime, resulting in a mosaic brain with specific neurons exhibiting variable and often extreme CAG lengths, ultimately leading to their death. Genome-wide association studies have identified genetic variants—both cis and trans, including mismatch repair modifiers—that modulate SI, as shown in blood cells, and influence HD’s age of onset. This review will explore the evidence for SI in HD and its role in disease pathogenesis, as well as the therapeutic implications of these findings. We conclude by emphasizing the urgent need for reliable methods to quantify SI for diagnostic and prognostic purposes.
Fast intraoperative detection of primary central nervous system lymphoma and differentiation from common central nervous system tumors using stimulated Raman histology and deep learning
Authors: Reinecke David , Maarouf Nader , Smith Andrew , Alber Daniel , Markert John , Goff Nicolas K , Hollon Todd C , Chowdury Asadur , Jiang Cheng , Hou Xinhai , Meissner Anna-Katharina , Fürtjes Gina , Ruge Maximilian I , Ruess Daniel , Stehle Thomas , Al-Shughri Abdulkader , Körner Lisa I , Widhalm Georg , Roetzer-Pejrimovsky Thomas , Golfinos John G , Snuderl Matija , Neuschmelting Volker , Orringer Daniel A
Published: December 2024

Background

Accurate intraoperative diagnosis is crucial for differentiating between primary central nervous system (CNS) lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge.

Methods

We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within <3 min. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and 2 additional independent test cohorts. We trained on 54 000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/nonneoplastic lesions. Training and test data were collected from 4 tertiary international medical centers. The final histopathological diagnosis served as ground truth.

Results

In the prospective test cohort of PCNSL and non-PCNSL entities (n = 160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ± 0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n = 420, n = 59) reached balanced accuracy rates of 95.44% ± 0.74 and 95.57% ± 2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma’s capabilities to detect class-specific histomorphological key features.

Conclusions

RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within 3 min, enabling fast clinical decision-making and subsequent treatment strategy planning.
Level I and II deficits—A clinical survey on international practice of awake craniotomy and definitions of postoperative “major” and “minor” deficits
Authors: Vooijs Manuela , Robertson Faith C , Blitz Sarah E , Jungk Christine , Krieg Sandro M , Schucht Philippe , De Vleeschouwer Steven , Vincent Arnaud J P E , Berger Mitchel S , Nahed Brian V , Broekman Marike L D , Gerritsen Jasper K W
Published: December 2024

Background

Awake craniotomy (AC) is a technique that balances maximum resection and minimal postoperative deficits in patients with intracranial tumors. To aid in the comparability of functional outcomes after awake surgery, this study investigated its international practice and aimed to define categories of postoperative deficits.

Methods

A survey was distributed via neurosurgical networks in Europe (European Association of Neurosurgical Societies, EANS), the Netherlands (Nederlandse Vereniging voor Neurochirurgie, NVVN), Belgium (Belgian Society of Neurosurgery, BSN), and the United States (Congress of Neurological Surgeons, CNS) between April 2022 and April 2023. Questions involved decision-making, including patient selection, anxiety assessment, and termination of resection. Interpretation of “major” and “minor” deficits, respectively labeled “level I” and “level II,” was assessed.

Results

Three hundred and ninety-five neurosurgeons from 46 countries completed the survey. Significant heterogeneity was found in the domains of indications, anxiety assessment, seizure management, and termination of resection. Moreover, the interpretation of “major” deficits mainly included language and motor impairments. Analysis across deficit categories showed significant overlap in the domains of executive function, social cognition, and vision. Secondly, “minor” deficits and “minor cognitive” deficits showed vast overlap.

Conclusions

This survey demonstrates high variability between neurosurgeons in AC practice across multiple domains, inviting international efforts to reach a consensus regarding the standardization and grading of postoperative deficits. The proposed categories of “level I” and “level II” deficits may aid in this standardization. It allows for systematic assessment of the benefit of surgery in neuro-oncology patients and allows for comparison of surgical outcomes between institutions and surgeons. This may help to optimize international guidelines for surgical neuro-oncology, including AC.
Stalking the stalk: Isolated pituitary stalk thickening and predictive factors for proliferative disease
Authors: Bennett Julie , Nobre Liana , Bouffet Eric , Abla Oussama , Maguire Bryan , Amirabadi Afsaneh , Hawkins Cynthia , Wasserman Jonathan D , Ertl-Wagner Birgit , Bartels Ute
Published: December 2024

Background

Few studies have evaluated predictive factors of isolated pituitary stalk thickening (iPST) in children.

Methods

In this retrospective study, radiology, endocrinology, and neuro-oncology databases were interrogated to identify patients with iPST between January 2000 and June 2019. A blinded, longitudinal assessment of MRIs was performed using quantitative, semi-quantitative, and qualitative metrics. Neuroimaging parameters were correlated to clinical parameters.

Results

Forty-seven patients were identified, with 40 meeting the inclusion criteria. Median age at baseline MRI was 9.6 years (range 0.9–17.5) with median follow-up of 5.2 years (range 0.3–18.6). Twenty-five (63%) were female. Thirty-four (85%) had pituitary dysfunction, including 31 with central diabetes insipidus (cDI). cDI was not predictive of proliferative disease (PfD): 69% of those with presumed primary hypophysitis (PPH) versus 93% with PfD (P = .1). Fourteen (35%) patients were diagnosed with PfD (germinoma = 8, Langerhans cell histiocytosis = 5, lymphoma = 1) at median of 1.3 years (range 0.3–4.0) after initial MRI. Progressive thickening of the stalk over time was associated with PfD (86% vs 4% in PPH, P < .0001), as was thickening of the entire stalk (56% in PfD vs 27% in PPH, P < .0001) with different imaging trends over time observed in PfD versus PPH. A “sack of marbles” appearance with heterogeneous enhancement on post-contrast imaging was associated with germinoma.

Conclusions

In this cohort, 35% of children with iPST were diagnosed with PfD. The association of cDI and PfD was not statistically significant. Progressive thickening of the entire stalk was predictive of PfD and a “sack of marbles” pattern was found to be highly suggestive of germinoma.
The evolution of chemical ordering and property in Fe1+xSe2 upon intercalation ratios
Authors: Zhao Zijing , Han Xiaocang , Zhu Shengcai , Fang Zhi , Han Ziyi , Liang Zhongyu , Li Bailing , Zhang Biao , Li Wei , Luo Zhaochu , Peng Licong , Zhao Xiaoxu , Li Xiangguo , Zhou Jiadong , Gao Song , Wang Chengxin , Kläui Mathias , Hou Yanglong
Published: December 2024

Intercalation has been considered as an effective method to explore innovative two-dimensional (2D) materials and modify their properties. However, the relationship between intercalation concentration, structure, and property remains a largely uncharted territory, and the controllable synthesis of desired intercalated phases faces challenges. Here, a general intercalated rule for the effect of self-intercalation ratio on atomic arrangements is revealed. Then, the controllable synthesis of a series of Fe-intercalated 2D materials is realized. Scanning transmission electron microscopy illustrates that their intercalation structures undergo disordered/ordered/half-ordered/ordered transformation, which confirms the intercalated rule and proposes a new structure termed half-ordered intercalation. Notably, their magnetic and electrical properties can be significantly modulated by intercalation. Orderly intercalated nanoflakes possess room-temperature magnetism with composition-regulated magnetic domains. Moreover, Fe1.5Se2 and Fe1.6Se2 are scarce half-metallic materials showing different magneto-resistance behaviors. This work would guide the design and synthesis of new intercalated materials, and deepen the understanding of the relationship between structure and properties.