bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children’s Oncology Group
Authors: Martin-Giacalone Bailey A , Richard Melissa A , Scheurer Michael E , Khan Javed , Sok Pagna , Shetty Priya B , Chanock Stephen J , Li Shengchao Alfred , Yeager Meredith , Marquez-Do Deborah A , Barkauskas Donald A , Hall David , McEvoy Matthew T , Brown Austin L , Sabo Aniko , Scheet Paul , Huff Chad D , Skapek Stephen X , Hawkins Douglas S , Venkatramani Rajkumar , Mirabello Lisa , Lupo Philip J 
Published: March 2023

Abstract

Background
Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS.

Methods
The study included 920 individuals with newly diagnosed RMS who were enrolled in Children’s Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group.

Results
We identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10−9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10−8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10−8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10−8) were associated with worse OS among individuals with alveolar RMS.

Conclusions
We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols.
Effects of floral traits on geitonogamous selfing rates and reproductive success in a protandrous species
Authors: Hou Meng , Zhao Zhi-Gang 
Published: March 2023

Abstract
Through its role in regulating pollinator behavior, floral display size and nectar gradient within inflorescences may alter the extent of geitonogamy and thus female reproductive success in protandrous species. However, this has seldom been examined. By quantifying selfing rate, seed number and male donor number, we estimated the effects of floral display size, nectar gradient and their interactions on plant reproduction in protandrous Aconitum gymnandrum. At plant level, selfing rate and seed number increased with a larger floral display of both main and lateral inflorescences but reduced with a declining nectar gradient. The effects of floral display of the main inflorescence on selfing rate and seed number were altered by the nectar gradient and floral display of lateral inflorescences as shown by their interactions. Larger floral display of the main inflorescence reduced male donor diversity. At flower level, the selfing rate and the seed number varied among flower positions, in which bottom flowers had lower selfing rate and higher seed number than top flowers. The effects of floral traits on geitonogamous selfing rate and seed number were inconsistent among flower positions. Although low cost of geitonogamous selfing for reproduction was tested by hand-pollination, the selfing rate was negatively correlated with seed number and male donor number in open-pollinated population. Our results suggest the potential role of trade-off between geitonogamy cost and reproductive benefit in evolution of floral traits. The variation of selfing rate and reproductive success among flowers may alter the trade-off and thus complicate evolution of traits.
The combination of astragaloside IV and Panax notoginseng saponins attenuates cerebral ischaemia–reperfusion injury in rats through ferroptosis and inflammation inhibition via activating Nrf2
Authors: Kang Zhineng , Xiao Qian , Wang Linlin , Xiao Lan , Tang Biao 
Published: March 2023

Abstract

Objectives
This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia–reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on ferroptosis and inflammatory response.

Methods
The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague–Dawley rat middle cerebral artery ischaemia–occlusion–reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol.

Key findings
After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and glutathione peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS.

Conclusions
The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit ferroptosis and inflammatory responses.
CLPB3 is required for the removal of chloroplast protein aggregates and thermotolerance in Chlamydomonas
Authors: Kreis Elena , Niemeyer Justus , Merz Marco , Scheuring David , Schroda Michael 
Published: March 2023

Abstract
In the cytosol of plant cells, heat-induced protein aggregates are resolved by the CASEIN LYTIC PROTEINASE/HEAT SHOCK PROTEIN 100 (CLP/HSP100) chaperone family member HSP101, which is essential for thermotolerance. For the chloroplast family member CLPB3 this is less clear, with controversial reports on its role in conferring thermotolerance. To shed light on this issue, we have characterized two clpb3 mutants in Chlamydomonas reinhardtii. We show that chloroplast CLPB3 is required for resolving heat-induced protein aggregates containing stromal TRIGGER FACTOR (TIG1) and the small heat shock proteins 22E/F (HSP22E/F) in vivo, and for conferring thermotolerance under heat stress. Although CLPB3 accumulation is similar to that of stromal HSP70B under ambient conditions, we observed no prominent constitutive phenotypes. However, we found decreased accumulation of the PLASTID RIBOSOMAL PROTEIN L1 (PRPL1) and increased accumulation of the stromal protease DEG1C in the clpb3 mutants, suggesting that a reduction in chloroplast protein synthesis capacity and an increase in proteolytic capacity may compensate for loss of CLPB3 function. Under ambient conditions, CLPB3 was distributed throughout the chloroplast, but reorganized into stromal foci upon heat stress, which mostly disappeared during recovery. CLPB3 foci were localized next to HSP22E/F, which accumulated largely near the thylakoid membranes. This suggests a possible role for CLPB3 in disentangling protein aggregates from the thylakoid membrane system.
High temperature defense pathways mediate lodicule expansion and spikelet opening in maize tassels
Authors: Liu Xiaoli , Gu Mingqi , Lv Xuanlong , Sheng Dechang , Wang Xin , Wang Pu , Huang Shoubing 
Published: March 2023

AbstractHigh temperature (HT) at flowering hinders pollen shedding, but the mechanisms underlying stress-induced spikelet closure are poorly understood in maize. In this study, yield components, spikelet opening, and lodicule morphology/protein profiling upon HT stress during flowering were examined in two contrasting maize inbred lines, Chang 7-2 and Qi 319. HT induced spikelet closure and reduced pollen shed weight (PSW) and seed set in both lines, but Qi 319 had a 7-fold lower PSW than Chang 7-2, and was thus more susceptible to HT. In Qi 319, a smaller lodicule size reduced the spikelet opening rate and angle, and relatively more vascular bundles hastened lodicule shrinking compared with Chang 7-2. Lodicules were collected for proteomics analysis. In lodicules of HT-stressed plants, proteins involved in stress signals, cell wall, cell constructure, carbohydrate metabolism, and phytohormone signaling were associated with stress tolerance. HT down-regulated the expression of ADP-ribosylation factor GTPase-activating protein domain2, SNAP receptor complex member11, and sterol methyltransferase2 in Qi 319 but not in Chang 7-2, which was in good agreement with the observed changes in protein abundance. Exogenous epibrassinolide increased the spikelet opening angle and extended the duration of spikelet opening. These results suggest that dysfunction of the actin cytoskeleton and membrane remodeling induced by HT probably limits lodicule expansion. In addition, a reduction in the vascular bundles in the lodicules and application of epibrassinolide might confer spikelet tolerance to HT stress.
The 3D genome and its impacts on human health and disease
Authors: Wang Siqi , Luo Zhengyu , Liu Weiguang , Hu Tengfei , Zhao Zhongying , Rosenfeld Michael G , Song Xiaoyuan 
Published: March 2023

Abstract
Eukaryotic genomes are highly compacted in the cell nucleus. Two loci separated by a long linear distance can be brought into proximity in space through DNA-binding proteins and RNAs, which contributes profoundly to the regulation of gene expression. Recent technology advances have enabled the development and application of the chromosome conformation capture (3C) technique and a host of 3C-based methods that enable genome-scale investigations into changes in chromatin high-order structures during diverse physiological processes and diseases. In this review, we introduce 3C-based technologies and discuss how they can be utilized to glean insights into the impacts of three-dimensional (3D) genome organization in normal physiological and disease processes.
Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content
Authors: Ma Tiantian , Mao Wei , Zhang Shaohua , Wang Yaqing , Wang Tao , Liu Jinghua , Shi Lei , Yu Xiang , Xue Rong , Shui Guanghou , Xu Zhiheng 
Published: March 2023

Abstract
Lipid-rich myelin is a special structure formed by oligodendrocytes wrapping neuronal axons. Abnormal myelin sheath is associated with many neurological diseases. Meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) plays an important role in vesicle trafficking from the endoplasmic reticulum (ER) to Golgi, and conditional knockout (cKO) of Mea6 in the brain significantly affects neural development and brain function. However, whether the impaired brain function involves the development of oligodendrocytes and white matter beyond neurons remains unclear. In this study, by using different models of diffusion magnetic resonance imaging, we showed that cKO of Mea6 in oligodendrocytes leads to significant impairment of the gross and microstructure of the white matter, as well as a significant decrease of cholesterol and triglycerides in brains. Our lipidomic analysis of purified myelin sheath for the first time showed that Mea6 elimination in oligodendrocytes significantly altered the lipid composition in myelin lipidome, especially the proportion of very long chain fatty acids (VLCFAs). In particular, the levels of most VLCFA-containing phosphatidylcholines were substantially lower in the myelin sheath of the cKO mice. The reduction of VLCFAs is likely due to the downregulated expression of elongation of very long chain fatty acids (ELOVLs). Our study of an animal model with white matter malformation and the comprehensive lipid profiling would provide clues for future studies of the formation of myelin sheath, myelin lipids, and the pathogenesis of white matter diseases.
Accurate model of the projected velocity distribution of galaxies in dark matter haloes
Authors: Aung Han , Nagai Daisuke , Rozo Eduardo , Wolfe Brandon , Adhikari Susmita 
Published: March 2023

ABSTRACT
We present a per cent-level accurate model of the line-of-sight velocity distribution of galaxies around dark matter haloes as a function of projected radius and halo mass. The model is developed and tested using synthetic galaxy catalogues generated with the UniverseMachine run on the Multi-Dark Planck 2 N-body simulations. The model decomposes the galaxies around a cluster into three kinematically distinct classes: orbiting, infalling, and interloping galaxies. We demonstrate that: (1) we can statistically distinguish between these three types of galaxies using only projected line-of-sight velocity information; (2) the halo edge radius inferred from the line-of-sight velocity dispersion is an excellent proxy for the three-dimensional halo edge radius; and (3) we can accurately recover the full velocity dispersion profile for each of the three populations of galaxies. Importantly, the velocity dispersion profiles of the orbiting and infalling galaxies contain five independent parameters – three distinct radial scales and two velocity dispersion amplitudes – each of which is correlated with mass. Thus, the velocity dispersion profile of galaxy clusters has inherent redundancies that allow us to perform non-trivial systematics checks from a single data set. We discuss several potential applications of our new model for detecting the edge radius and constraining cosmology and astrophysics using upcoming spectroscopic surveys.
Collisional evolution of dust and water ice in protoplanetary discs during and after an accretion outburst
Authors: Houge Adrien , Krijt Sebastiaan 
Published: March 2023

ABSTRACTMost protoplanetary discs are thought to undergo violent and frequent accretion outbursts, during which the accretion rate and central luminosity are elevated for several decades. This temporarily increases the disc temperature, leading to the sublimation of ice species as snowlines move outwards. In this paper, we investigate how an FUor-type accretion outburst alters the growth and appearance of dust aggregates at different locations in protoplanetary discs. We develop a model based on the Monte Carlo approach to simulate locally the coagulation and fragmentation of icy dust particles and investigate different designs for their structure and response to sublimation. Our main finding is that the evolution of dust grains located between the quiescent and outburst water snowlines is driven by significant changes in composition and porosity. The time required for the dust population to recover from the outburst and return to a coagulation/fragmentation equilibrium depends on the complex interplay of coagulation physics and outburst properties, and can take up to 4500 yr at 5 au. Pebble-sized particles, the building blocks of planetesimals, are either deprecated in water ice or completely destroyed, respectively, resulting in drier planetesimals or halting their formation altogether. When accretion outbursts are frequent events, the dust can be far from collisional equilibrium for a significant fraction of time, offering opportunities to track past outbursts in discs at millimetre wavelengths. Our results highlight the importance of including accretion outbursts in models of dust coagulation and planet formation.
Investigation of a small X-ray flaring event in NLS1 galaxy NGC 4051
Authors: Kumari Neeraj , Jana Arghajit , Naik Sachindra , Nandi Prantik 
Published: March 2023

ABSTRACT
We performed a detailed broad-band spectral and timing analysis of a small flaring event of ∼120 ks in the narrow-line Seyfert 1 galaxy NGC 4051 using simultaneous XMM–Newton and NuSTAR observations. The ∼300 ks long NuSTAR observation and the overlapping XMM–Newton exposure were segregated into pre-flare, flare, and post-flare segments. During the flare, the NuSTAR count rate peaked at 2.5 times the mean count rate before the flare. Using various physical and phenomenological models, we examined the 0.3–50 keV X-ray spectrum, which consists of a primary continuum, reprocessed emission, warm absorber and ultrafast outflows at different time-scales. The mass of the central black hole is estimated to be ≥1.32 × 105 M⊙ from spectral analysis. The absence of correlation between the flux in the 6–7 keV and 10–50 keV bands suggests different origins of the iron emission line and the Compton hump. From the spectral analysis, we found that the reflection fraction drops significantly during the flare, accompanied by an increase in the coronal height above the disc. The spectrum became soft during the flare, supporting the ‘softer when brighter’ nature of the source. After the alleviation of the flare, the coronal height drops and the corona heats up. This indicates that there could be inflation of the corona during the flare. We found no significant change in the inner accretion disc or the seed photon temperature. These results suggest that the flaring event occurred due to a change in coronal properties rather than any notable change in the accretion disc.
A trail of the invisible: blue globular clusters trace the radial density distribution of the dark matter – case study of NGC 4278
Authors: Kluge Matthias , Remus Rhea-Silvia , Babyk Iurii V , Forbes Duncan A , Dolfi Arianna 
Published: March 2023

ABSTRACTWe present new, deep optical observations of the early-type galaxy NGC 4278, which is located in a small loose group. We find that the galaxy lacks fine substructure, that is, it appears relaxed, out to a radius of ∼70 kpc. Our g- and i-band surface brightness profiles are uniform down to our deepest levels of ∼28 mag arcsec−2. This spans an extremely large radial range of more than 14 half-mass radii. Combined with archival globular cluster (GC) number density maps and a new analysis of the total mass distribution obtained from archival Chandra X-ray data, we find that the red GC subpopulation traces well the stellar mass density profile from 2.4 out to even 14 half-mass radii, while the blue GC subpopulation traces the total mass density profile of the galaxy over a large radial range. Our results reinforce the scenario that red GCs form mostly in situ along with the stellar component of the galaxy, while the blue GCs are more closely aligned with the total mass distribution in the halo and were accreted along with halo matter. We conclude that for galaxies where the X-ray emission from the hot halo is too faint to be properly observable and as such is not available to measure the dark matter profile, the blue GC population can be used to trace this dark matter component out to large radii.
Population III star formation in an X-ray background: III. Periodic radiative feedback and luminosity induced by elliptical orbits
Authors: Park Jongwon , Ricotti Massimo , Sugimura Kazuyuki 
Published: March 2023

ABSTRACTWe model Pop III star formation in different FUV and X-ray backgrounds, including radiation feedback from protostars. We confirm previous results that a moderate X-ray background increases the number of Pop III systems per unit cosmological volume, but masses and multiplicities of the system are reduced. The stellar mass function also agrees with previous results, and we confirm the outward migration of the stars within the protostellar discs. We find that nearly all Pop III star systems are hierarchical, i.e. binaries of binaries. Typically, two equal-mass stars form near the centre of the protostellar disc and migrate outwards. Around these stars, mini-discs fragment forming binaries that also migrate outwards. Stars may also form at Lagrange points L4/L5 of the system. Afterwards, star formation becomes more stochastic due to the large multiplicity, and zero-metallicity low-mass stars can form when rapidly ejected from the disc. Stars in the disc often have eccentric orbits, leading to a periodic modulation of their accretion rates and luminosities. At the pericentre, due to strong accretion, the star can enter a red-supergiant phase reaching nearly Eddington luminosity in the optical bands (mAB ∼ 34 for a 100 M⊙ star at z = 6). During this phase, the star, rather than its nebular lines, can be observed directly by JWST, if sufficiently magnified by a gravitational lens. The ∼10 000 AU separations and high eccentricities of many Pop III star binaries in our simulations are favourable parameters for IMBH mergers – and gravitational waves emission – through orbital excitation by field stars.
RNA binding proteins Smaug and Cup induce CCR4–NOT-dependent deadenylation of the nanos mRNA in a reconstituted system
Authors: Pekovic Filip , Rammelt Christiane , Kubíková Jana , Metz Jutta , Jeske Mandy , Wahle Elmar 
Published: March 2023

Abstract
Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior – posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug, which binds to Smaug recognition elements (SREs) in the nanos 3’-UTR and nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4–NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4–NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4–NOT complexes in an SRE-dependent manner. CCR4–NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4–NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4–NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has a minor inhibitory effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4–NOT-dependent deadenylation, both independently and in cooperation with Smaug.