bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asteroseismic signatures of core magnetism and rotation in hundreds of low-luminosity red giants
Authors: Hatt Emily J , Ong J M Joel , Nielsen Martin B , Chaplin William J , Davies Guy R , Deheuvels Sébastien , Ballot Jérôme , Li Gang , Bugnet Lisa 
Published: September 2024

ABSTRACT
Red giant stars host solar-like oscillations which have mixed character, being sensitive to conditions both in the outer convection zone and deep within the interior. The properties of these modes are sensitive to both core rotation and magnetic fields. While asteroseismic studies of the former have been done on a large scale, studies of the latter are currently limited to tens of stars. We aim to produce the first large catalogue of both magnetic and rotational perturbations. We jointly constrain these parameters by devising an automated method for fitting the power spectra directly. We successfully apply the method to 302 low-luminosity red giants. We find a clear bimodality in core rotation rate. The primary peak is at $\delta \nu _{\mathrm{rot}}$ = 0.32 $\mu$Hz, and the secondary at $\delta \nu _{\mathrm{rot}}$ = 0.47 $\mu$Hz. Combining our results with literature values, we find that the percentage of stars rotating much more rapidly than the population average increases with evolutionary state. We measure magnetic splittings of 2$\sigma$ significance in 23 stars. While the most extreme magnetic splitting values appear in stars with masses $\gt $1.1 M$_{\odot }$, implying they formerly hosted a convective core, a small but statistically significant magnetic splitting is measured at lower masses. Asymmetry between the frequencies of a rotationally split multiplet has previously been used to diagnose the presence of a magnetic perturbation. We find that of the stars with a significant detection of magnetic perturbation, 43 per cent do not show strong asymmetry. We find no strong evidence of correlation between the rotation and magnetic parameters.
The VISCACHA Survey – XI. Benchmarking SIESTA: a new synthetic CMD fitting code
Authors: Ferreira Bernardo P L , Jr. João F C Santos , Dias Bruno , Maia Francisco F S , Kerber Leandro O , Gardin João Francisco , Oliveira Raphael A P , Westera Pieter , Rocha João Pedro S , Souza Stefano O , Hernandez-Jimenez Jose A , Santrich Orlando Katime , Villegas Angeles Pérez , Garro Elisa R , Baume Gustavo L , Fernández-Trincado José G , de Bórtoli Bruno , Parisi Maria Celeste , Bica Eduardo 
Published: September 2024

ABSTRACT
We present a novel code, named SIESTA (Statistical matchIng between rEal and Synthetic sTellar popuLations), designed for performing statistical isochrone fitting to colour–magnitude diagrams (CMDs) of single stellar populations by leveraging comparisons between the observed stellar distribution and predictions from synthetic populations, simulated on top of a grid of isochrones. These synthetic populations encompass determinant factors such as the cluster’s initial mass function (IMF), the presence of non-resolved binaries, as well as the expected photometric errors, and observational completeness (or the observed luminosity function). Employing Markov Chain Monte Carlo within a Bayesian framework, SIESTA allows for the determination of a cluster’s age, metallicity, distance, colour excess, and binary fraction (with masses exceeding a certain ratio). In this study, we rigorously benchmark the SIESTA code utilizing synthetic populations and evaluate its performance against observations from the VISCACHA Survey in the Small Magellanic Cloud, focusing on five star clusters: Lindsay 114, NGC 152, Lindsay 91, Lindsay 113, and NGC 121. These clusters were chosen for their diverse age range, spanning from 0.04 to 10 Gyr. Our findings demonstrate the capability of the SIESTA code to accurately represent the observed CMDs of these clusters. Furthermore, we compare the results obtained with SIESTA to previous characterizations of these clusters, highlighting the consistency between the derived metallicity and spectroscopic determinations from various sources.
Identification of transcription factor co-binding patterns with non-negative matrix factorization
Authors: Rauluseviciute Ieva , Launay Timothée , Barzaghi Guido , Nikumbh Sarvesh , Lenhard Boris , Krebs Arnaud Regis , Castro-Mondragon Jaime A , Mathelier Anthony 
Published: September 2024

Abstract
Transcription factor (TF) binding to DNA is critical to transcription regulation. Although the binding properties of numerous individual TFs are well-documented, a more detailed comprehension of how TFs interact cooperatively with DNA is required. We present COBIND, a novel method based on non-negative matrix factorization (NMF) to identify TF co-binding patterns automatically. COBIND applies NMF to one-hot encoded regions flanking known TF binding sites (TFBSs) to pinpoint enriched DNA patterns at fixed distances. We applied COBIND to 5699 TFBS datasets from UniBind for 401 TFs in seven species. The method uncovered already established co-binding patterns and new co-binding configurations not yet reported in the literature and inferred through motif similarity and protein-protein interaction knowledge. Our extensive analyses across species revealed that 67% of the TFs shared a co-binding motif with other TFs from the same structural family. The co-binding patterns captured by COBIND are likely functionally relevant as they harbor higher evolutionarily conservation than isolated TFBSs. Open chromatin data from matching human cell lines further supported the co-binding predictions. Finally, we used single-molecule footprinting data from mouse embryonic stem cells to confirm that the COBIND-predicted co-binding events associated with some TFs likely occurred on the same DNA molecules.
The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys isoacceptors in the P site
Authors: Turnbull Kathryn , Paternoga Helge , von der Weth Esther , Egorov Artyom A , Pochopien Agnieszka A , Zhang Yujie , Nersisyan Lilit , Margus Tõnu , Johansson Marcus J O , Pelechano Vicent , Wilson Daniel N , Hauryliuk Vasili 
Published: September 2024

Abstract
The efficiency of translation termination is determined by the nature of the stop codon as well as its context. In eukaryotes, recognition of the A-site stop codon and release of the polypeptide are mediated by release factors eRF1 and eRF3, respectively. Translation termination is modulated by other factors which either directly interact with release factors or bind to the E-site and modulate the activity of the peptidyl transferase center. Previous studies suggested that the Saccharomyces cerevisiae ABCF ATPase New1 is involved in translation termination and/or ribosome recycling, however, the exact function remained unclear. Here, we have applied 5PSeq, single-particle cryo-EM and readthrough reporter assays to provide insight into the biological function of New1. We show that the lack of New1 results in ribosomal stalling at stop codons preceded by a lysine or arginine codon and that the stalling is not defined by the nature of the C-terminal amino acid but rather by the identity of the tRNA isoacceptor in the P-site. Collectively, our results suggest that translation termination is inefficient when ribosomes have specific tRNA isoacceptors in the P-site and that the recruitment of New1 rescues ribosomes at these problematic termination contexts.
Machine learning unravels inherent structural patterns in Escherichia coli Hi-C matrices and predicts chromosome dynamics
Authors: Bera Palash , Mondal Jagannath 
Published: September 2024

Abstract
High dimensional nature of the chromosomal conformation contact map (‘Hi-C Map’), even for microscopically small bacterial cell, poses challenges for extracting meaningful information related to its complex organization. Here we first demonstrate that an artificial deep neural network-based machine-learnt (ML) low-dimensional representation of a recently reported Hi-C interaction map of archetypal bacteria Escherichia coli can decode crucial underlying structural pattern. The ML-derived representation of Hi-C map can automatically detect a set of spatially distinct domains across E. coli genome, sharing reminiscences of six putative macro-domains previously posited via recombination assay. Subsequently, a ML-generated model assimilates the intricate relationship between large array of Hi-C-derived chromosomal contact probabilities and respective diffusive dynamics of each individual chromosomal gene and identifies an optimal number of functionally important chromosomal contact-pairs that are majorly responsible for heterogenous, coordinate-dependent sub-diffusive motions of chromosomal loci. Finally, the ML models, trained on wild-type E. coli show-cased its predictive capabilities on mutant bacterial strains, shedding light on the structural and dynamic nuances of ΔMatP30MM and ΔMukBEF22MM chromosomes. Overall our results illuminate the power of ML techniques in unraveling the complex relationship between structure and dynamics of bacterial chromosomal loci, promising meaningful connections between ML-derived insights and biological phenomena.
Structural basis for the concerted antiphage activity in the SIR2–HerA system
Authors: Liao Fumeng , Yu Guimei , Zhang Chendi , Liu Zhikun , Li Xuzichao , He Qiuqiu , Yin Hang , Liu Xiang , Li Zhuang , Zhang Heng 
Published: September 2024

Abstract
Recently, a novel two-gene bacterial defense system against phages, encoding a SIR2 NADase and a HerA ATPase/helicase, has been identified. However, the molecular mechanism of the bacterial SIR2–HerA immune system remains unclear. Here, we determine the cryo-EM structures of SIR2, HerA and their complex from Paenibacillus sp. 453MF in different functional states. The SIR2 proteins oligomerize into a dodecameric ring-shaped structure consisting of two layers of interlocked hexamers, in which each subunit exhibits an auto-inhibited conformation. Distinct from the canonical AAA+ proteins, HerA hexamer alone in this antiphage system adopts a split spiral arrangement, which is stabilized by a unique C-terminal extension. SIR2 and HerA proteins assemble into a ∼1.1 MDa torch-shaped complex to fight against phage infection. Importantly, disruption of the interactions between SIR2 and HerA largely abolishes the antiphage activity. Interestingly, binding alters the oligomer state of SIR2, switching from a dodecamer to a tetradecamer state. The formation of the SIR2–HerA binary complex activates NADase and nuclease activities in SIR2 and ATPase and helicase activities in HerA. Together, our study not only provides a structural basis for the functional communications between SIR2 and HerA proteins, but also unravels a novel concerted antiviral mechanism through NAD+ degradation, ATP hydrolysis, and DNA cleavage.
ADAR3 modulates neuronal differentiation and regulates mRNA stability and translation
Authors: Karlström Victor , Sagredo Eduardo A , Planells Jordi , Welinder Charlotte , Jungfleisch Jennifer , Barrera-Conde Andrea , Engfors Linus , Daniel Chammiran , Gebauer Fátima , Visa Neus , Öhman Marie 
Published: September 2024

Abstract
ADAR3 is a catalytically inactive member of the family of adenosine deaminases acting on RNA (ADARs). Here we have investigated its function in the context of the developing mouse brain. The expression of ADAR3 gradually increases throughout embryogenesis and drops after birth. Using primary cortical neurons, we show that ADAR3 is only expressed in a subpopulation of in vitro differentiated neurons, which suggests specific functions rather than being a general regulator of ADAR editing in the brain. The analysis of the ADAR3 interactome suggested a role in mRNA stability and translation, and we show that expression of ADAR3 in a neuronal cell line that is otherwise ADAR3-negative changes the expression and stability of a large number of mRNAs. Notably, we show that ADAR3 associates with polysomes and inhibits translation. We propose that ADAR3 binds to target mRNAs and stabilizes them in non-productive polysome complexes. Interestingly, the expression of ADAR3 downregulates genes related to neuronal differentiation and inhibits neurofilament outgrowth in vitro. In summary, we propose that ADAR3 negatively regulates neuronal differentiation, and that it does so by regulating mRNA stability and translation in an editing-independent manner.
Modulation of dynamic DNA G-quadruplex structures in the hTERT promoter region by ligands
Authors: Karna Deepak , Liang Lin , Sharma Grinsun , Mandal Shankar , Asamitsu Sefan , Kawamoto Yusuke , Hashiya Kaori , Bando Toshikazu , Sugiyama Hiroshi , Mao Hanbin 
Published: September 2024

Abstract
Small molecules can inhibit cellular processes such as replication and transcription by binding to the promoter regions that are prone to form G-quadruplexes. However, since G-quadruplexes exist throughout the human genome, the G-quadruplex binders suffer from specificity issues. To tackle this problem, a G-quadruplex binder (Pyridostatin, or PDS) is conjugated with a ligand (Polyamide, or PA) that can specifically recognize DNA sequences flanking the G-quadruplex forming region. The binding mechanism of this hybrid ligand to the hTERT promoter region (hTERT 5–12) is then elucidated using optical tweezers. During mechanical unfolding processes, different intermediate structures of hTERT 5–12 in presence of PDS, PA, or PA-PDS conjugate are observed. These intermediate structures are consistent with two folding patterns of G-quadruplexes in the hTERT 5–12 fragment. While the duplex DNA binder PA facilitates the folding of a hairpin-G-quadruplex structure, the PDS assists the formation of two tandem G-quadruplexes. Both replication stop assay in vitro and dual luciferase assay in vivo established the effectiveness of the PA-PDS conjugate for hTERT 5–12 targeting. We expect such a ligand dependent folding dynamics will provide guidelines to the development of drugs that not only target hTERT expressions, but also other oncogenes via interactions with specific G-quadruplex structures formed in their promotor regions.
PARP1-TRIM44-MRN loop dictates the response to PARP inhibitors
Authors: Kim Yonghyeon , Min Sunwoo , Kim Soyeon , Lee Seo Yun , Park Yeon-Ji , Heo Yungyeong , Park Soon Sang , Park Tae Jun , Lee Jae-Ho , Kang Ho Chul , Ji Jae-Hoon , Cho Hyeseong 
Published: September 2024

Abstract
PARP inhibitors (PARPi) show selective efficacy in tumors with homologous recombination repair (HRR)-defects but the activation mechanism of HRR pathway in PARPi-treated cells remains enigmatic. To unveil it, we searched for the mediator bridging PARP1 to ATM pathways by screening 211 human ubiquitin-related proteins. We discovered TRIM44 as a crucial mediator that recruits the MRN complex to damaged chromatin, independent of PARP1 activity. TRIM44 binds PARP1 and regulates the ubiquitination-PARylation balance of PARP1, which facilitates timely recruitment of the MRN complex for DSB repair. Upon exposure to PARPi, TRIM44 shifts its binding from PARP1 to the MRN complex via its ZnF UBP domain. Knockdown of TRIM44 in cells significantly enhances the sensitivity to olaparib and overcomes the resistance to olaparib induced by 53BP1 deficiency. These observations emphasize the central role of TRIM44 in tethering PARP1 to the ATM-mediated repair pathway. Suppression of TRIM44 may enhance PARPi effectiveness and broaden their use even to HR-proficient tumors.
The Serine Shunt enables formate conversion to formaldehyde in vivo
Authors: Schann Karin , Wenk Sebastian 
Published: September 2024

Abstract
Microbial valorization of CO2-derived substrates has emerged as a promising approach to address climate change and resource scarcity. Formate, which can be efficiently produced from CO2, shows great potential as a sustainable feedstock for biotechnological production. However, the scope of formate assimilation pathways is restricted by the limited number of natural formate-assimilating enzymes. To overcome this limitation, several new-to-nature routes for formate assimilation based on its reduction to formaldehyde have been proposed, but they suffer from low catalytic efficiencies and cannot yet support bacterial growth. Here, we propose the Serine Shunt as a novel formate reduction route and demonstrate its activity in vivo. In this pathway, formate is attached to glycine to form serine, which is subsequently cleaved into formaldehyde and glycine, thereby effectively converting formate to formaldehyde. Unlike other formate reduction routes, the Serine Shunt mainly utilizes natural reactions with favorable enzyme kinetics, while requiring the same amount of ATP and NADPH as the most efficient new-to-nature route. We implemented the Serine Shunt in engineered Escherichia coli strains using a stepwise approach by dividing the pathway into metabolic modules. After validating the individual module activities, we demonstrated the in vivo activity of the complete Serine Shunt by measuring intracellular formaldehyde production with a green fluorescent protein (GFP) sensor and coupling its activity to cell growth. Our results indicate that the Serine Shunt could be applied as a novel formate reduction route in methylotrophic hosts relevant for biotechnology.
Sample Size Impact (SaSii): an R script for estimating optimal sample sizes in population genetics and population genomics studies
Authors: Scaketti Matheus , Sujii Patricia Sanae , Alves-Pereira Alessandro , Schwarcz Kaiser Dias , Francisconi Ana Flávia , Moro Matheus Sartori , Martins Kauanne Karolline Moreno , de Jesus Thiago Araujo , de Souza Guilherme Brener Ferreira , Zucchi Maria Imaculada 
Published: September 2024

AbstractObtaining large sample sizes for genetic studies can be challenging, time-consuming, and expensive. However, small sample sizes may generate biased or imprecise results. Many studies have suggested the minimum sample size necessary to obtain robust and reliable results, but it is not possible to define one ideal minimum sample size that fits all studies. Here, we aim to present SaSii (Sample Size Impact), a R script to help researchers to define minimum sample size and to indicate minimum sample size patterns for some taxa groups. The patterns were obtained by analyzing previously published datasets with SaSii and can be used as a starting point for the sample design of population genetics and genomic studies. Our results showed that it is possible to estimate an adequate sample size that accurately represents the real population and does not require the scientist to take time to write any program code, extract and sequence samples or use population genetics programs, making it easier to gather this information. We also confirmed that sample sizes of five to twenty-five for SNP and fifteen to thirty for SSR can be used for most plant species, giving a better direction for new studies.
Sec18 side-loading is essential for universal SNARE recycling across cellular contexts
Authors: Khan Yousuf A. , White K. Ian , Pfuetzner Richard A. , Singal Bharti , Esquivies Luis , Mckenzie Garvey , Liu Fang , DeLong Katherine , Choi Uchoer B. , Montabana Elizabeth , Mclaughlin Theresa , Wickner William T. , Brunger Axel T. 
Published: September 2024

SummarySNARE proteins drive membrane fusion as their core domains zipper into a parallel four-helix bundle1,2. After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/ α-SNAP3,4to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains5. Previous structures of the NSF–α-SNAP–SNARE complex revealed SNARE domain threaded through the D1 ATPase ring6, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems7. Here,in vivomass-spectrometry reveals N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. Cryo-EM structures of a yeast SNARE complex, Sec18, and Sec17 in a non-hydrolyzing condition shows SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side-loading and unloading topologically constrained SNARE substrates.
Unbiased preclinical phenotyping reveals neuroprotective properties of pioglitazone
Authors: Harding Edward C. , Chen Hsiao-Jou Cortina , Shepilov Dmytro , Zhang Stefanie O. , Rowley Christine , Mali Iman , Chen Jiahui , Stewart Natasha , Swinden Dean , Washer Sam J. , Bassett Andrew R. , Merkle Florian T. 
Published: September 2024

ABSTRACTAnimal models are essential for assessing the preclinical efficacy of candidate drugs, but animal data often fails to replicate in human clinical trials. This translational gulf is due in part to the use of models that do not accurately replicate human disease processes and phenotyping strategies that do not capture sensitive, disease-relevant measures. To address these challenges with the aim of validating candidate neuroprotective drugs, we combined a mouse prion (RML scrapie) model that recapitulates the key common features of human neurodegenerative disease including bona fide neuronal loss, with unbiased and machine learning-assisted behavioural phenotyping. We found that this approach measured subtle, stereotyped, and progressive changes in motor behaviour over the disease time course that correlated with the earliest detectable histopathological changes in the mouse brain. To validate the utility of this model system, we tested whether the anti-diabetic drug pioglitazone could slow prion disease progression. Pioglitazone crosses the blood-brain-barrier and has been shown to reduce neurodegenerative disease severity in other mouse models. We found that in addition to significantly slowing the emergence of early-stage clinical signs of neurodegeneration, pioglitazone significantly improved motor coordination throughout the disease time course and reduced neuronal endoplasmic reticulum stress. Together, these findings suggest that pioglitazone could have neuroprotective properties in humans, confirm the utility of the scrapie mouse model of neurodegeneration, and provide generalisable experimental and analysis methods for the generation of data-rich behavioural data to accelerate and improve preclinical validation.
Cell morphology and gene expression: tracking changes and complementarity across time and cell lines
Authors: Lejal Vanille , Rouquié David , Taboureau Olivier 
Published: September 2024

SummaryEffective drug discovery relies on combining target knowledge with functional assays and multi-omics data to understand chemicals’ molecular actions. However, the relationship between cell morphology and gene expression over time and across cell lines remains unclear. To explore this, we analyzed Cell Painting and L1000 data for 106 compounds across three cell lines from osteoblast, lung, and breast tumors (U2OS, A549, and MCF7) at three time points (6h, 24h, 48h) using a 10µM concentration. We found significant time and cell line effects in Cell Painting data, with less pronounced effects in transcriptomics. Using Weighted Gene Co-expression Network Analysis (WGCNA) and enrichment analysis, we identified connections between cell morphology and gene deregulation for chemicals with similar biological effects (e.g., HDAC and CDK inhibitors). These findings suggest that while Cell Painting shows distinct patterns, both technologies offer complementary insights into compound-induced cellular changes, enhancing drug discovery and chemical risk assessment.