bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthogonal RNA-regulated destabilization domains for three-color RNA imaging with minimal RNA perturbation
Authors: Pham Tien G. , Ajayi Omoyemi , Wu Jiahui 
Published: January 2025

ABSTRACTRNA-regulated destabilization domain allows live-cell imaging of single RNA. However, this method is limited to single-color RNA imaging and its long RNA tag induces destabilization of the tagged RNA. Here, we describe two orthogonal RNA-regulated destabilization domains that enable three-color mRNA imaging in living mammalian cells. One of these destabilizations can be combined with a short RNA tag (9XMS2) for single-molecule RNA imaging without perturbation of RNA stability.
High potential contribution of intercropping to soybean and maize self-sufficiency in Europe
Authors: Chen Mathilde , Guilpart Nicolas , Makowski David 
Published: January 2025

AbstractThe European Union is currently not self-sufficient in soybean and maize,1thus relying on imports.2According to results of fields experiments,3the simultaneous cultivation of soybeans and cereals – intercropping – could improve food self-sufficiency without increasing cultivated land, but this strategy has yet to be evaluated at the scale of the European Union. Here, we examine the potential for maize-soybean intercropping to improve the European Union’s self-sufficiency in soybean and maize without cropland expansion and by minimizing crop substitution. Our results suggest that achieving 50% (75%) soybean self-sufficiency in the European Union would require 13.1 (20.1) Mha under maize-soybean intercropping. When comparing the areas of cultivated land obtained either by growing the two species separately or together, we demonstrate that intercropping saves 27-30% of land compared with sole crops as soon as more soybean is produced in 1 ha of intercropping than in 0.5 ha of sole soybean. Ensuring European Union’s self-sufficiency in a sustainable way is a challenge requiring multiple solutions. Our results underline that intercropping is an effective strategy for improving the European Union’s soybean self-sufficiency, while satisfying maize needs and saving cultivated lands.
The role of prooxidants and antioxidants in shaping life-history and parasite tolerance inAnophelesmosquitoes
Authors: Zeferino Tiago G. , Mora Alfonso Rojas , Koella Jacob C. 
Published: January 2025

AbstractOxidative homeostasis plays important roles in physiology, for reactive oxygen species not only lead to damaging oxidative stress, but also regulate important physiological processes like immunity and longevity. ROS are therefore expected to be a key factor underlying many host-parasite interactions. We evaluated the role of the host’s oxidative status on the outcome of infection with the mosquitoAnopheles gambiaeinfected by the microsporidianVavraia culicis. To do so, we manipulated the oxidative status of the mosquitoes by feeding them early (the first four days after emergence) or late (from five days after emergence onwards) either a standard sugar source or one supplemented with a prooxidant (hydrogen peroxide) or antioxidant (vitamin C), and then measured the longevity and fecundity of uninfected and infected mosquitoes and (for infected mosquitoes) the parasite load at a given day (13 days after emergence) or when the mosquitoes died. The prooxidant generally increased longevity, but if consumed early after emergence its impact was lessened by the infection byVavraia. In contrast the antioxidant increased fecundity, and the impact was not affected by the status of infection or by the timing of consumption. Finally, early consumption of both supplements increasedVavraia’s spore load at 13 days after emergence and at death. In contrast, late consumption enhanced the parasite’s growth late in the mosquito’s life. Thus, our experiment revealed complex effects of prooxidant and antioxidant consumption, emphasising the critical role of timing and context in shaping their influence on biological traits.
Detecting Amino Acid Variants Using Next-Generation Protein Sequencing (NGPS)
Authors: Chinnaraj Mathivanan , Lin Jianan , Blacklock Kristin , Hermes Eric , Meyer Michael , Pike Douglas , Vieceli John , Chorny Ilya 
Published: January 2025

AbstractNext-Generation Protein Sequencing™(NGPS™) is a single-molecule approach for characterizing protein variants, offering detailed insight into proteoforms and amino acid substitutions not easily discerned by mass spectrometry. The novel data type produced by NGPS, which is based on binding of N-terminal amino acids by fluorescently tagged recognizer proteins, requires the development of new data analysis methods and bioinformatic tools. Here, we present ProteoVue™, a comprehensive bioinformatics pipeline for Single Amino Acid Variant (SAAV) detection and quantification using the Quantum-Si Platinum®NGPS platform. ProteoVue integrates multiple analytical components, including robust pulse-calling, recognition segment detection, fluorescence dye classification, and a neural network-driven kinetic signature database for pulse duration prediction. These components feed into a scoring-based alignment and clustering framework that enables accurate variant calling within binary peptide mixtures. We demonstrate that ProteoVue recovers expected variant ratios across diverse substitution types including residues that lack direct amino acid recognizers. While some extreme cases remain challenging, the pipeline consistently captures the key kinetic features required for variant discrimination, underscoring its potential as a versatile and powerful tool for proteomic studies. As NGPS technology matures and recognizer libraries expand, ProteoVue provides a foundation for increasingly refined variant analysis in basic research, biomarker discovery, and clinical applications.
OPUS-GO: An interpretable protein/RNA sequence annotation framework based on biological language model
Authors: Xu Gang , Lv Ying , Zhang Ruoxi , Xia Xinyuan , Wang Qinghua , Ma Jianpeng 
Published: January 2025

AbstractAccurate annotation of protein and RNA sequences is essential for understanding their structural and functional attributes. However, due to the relative ease of obtaining whole sequence-level annotations compared to residue-level annotations, existing biological language model (BLM)-based methods often prioritize enhancing sequence-level classification accuracy while neglecting residue-level interpretability. To address this, we introduce OPUS-GO, which exclusively utilizes sequence-level annotations to provide both sequence-level and residue-level classification results. In other words, OPUS-GO not only provides the sequence-level annotations but also offers the rationale behind these predictions by pinpointing their corresponding most critical residues within the sequence. Our results show that, by leveraging features derived from BLMs and our modified Multiple Instance Learning (MIL) strategy, OPUS-GO exhibits superior sequence-level classification accuracy compared to baseline methods in most downstream tasks. Furthermore, OPUS-GO demonstrates robust interpretability by accurately identifying the residues associated with the corresponding labels. Additionally, the OPUS-GO framework can be seamlessly integrated into any language model, enhancing both accuracy and interpretability for their downstream tasks.
Transitory impact of subclinicalShigellainfections on biomarkers of environmental enteropathy in children under 2 years
Authors: Liakakos Haley A. , Platts-Mills James A. , Quesada Maria Garcia , Liu Jie , Houpt Eric R. , Rogawski McQuade Elizabeth T. 
Published: January 2025

AbstractClinical and subclinicalShigellainfections among children living in low- and middle-income countries (LMICs) have been associated with long-term adverse effects such as impaired linear growth. The mechanism for the impact of subclinical infections has been theorized to occur through contributions to environmental enteropathy (EE). WhileShigellahas previously been associated with biomarkers of EE at the time of infection, we evaluated whether this impact was sustained after infections, which would support EE being the mechanism for the effects ofShigellaon growth. A prospective birth cohort study of 1,715 children living in 8 different LMICs was conducted. Over the course of 24 months, monthly non-diarrheal stool samples were analyzed for subclinicalShigellainfections through quantitative PCR methods. EE was reflected by elevated concentrations of 3 fecal biomarkers: myeloperoxidase (MPO), neopterin (NEO), and alpha-1-antitrypsin (AAT). MPO concentrations were found to be significantly higher by 0.30 log(nm/mL) (95% CI: 0.23, 0.37) in the initial month ofShigelladetection among stools with subclinicalShigellainfections. After theShigellainfection, MPO concentrations declined throughout the following 6 months, and concentrations were lower by 6 months post-infection [MPO 6-month difference: -0.16 log(nm/mL) (95% CI: -0.26, -0.04)]. SubclinicalShigellainfections had no effect on NEO concentration levels within the initial month ofShigelladetection but did decrease post-infection. SubclinicalShigellainfections had no effect on AAT concentration levels until 6 months post-infection [AAT difference: -0.13 log(mg/g) (95% CI: - 0.24, -0.03)]. These findings did not differ by antibiotic use around time of index infection. The impact ofShigellaon biomarkers of EE was not sustained, suggesting the negative association betweenShigellaand growth could be explained by the accumulation of time-limited rather than persistent effects on inflammation.
Architectural singularities in wild Coffea (Baracoffea) species: integrated morphological perspectives for climate-resilient coffee cultivation
Authors: Bezandry Rickarlos , Guyot Romain , Ranarijaona Hery Lisy Tiana , Sabatier Sylvie , Vavitsara Marie Elodie , Anest Artemis 
Published: January 2025

AbstractGlobal coffee production faces increasing threats from climate change, including rising temperatures, prolonged droughts, and spreads of diseases. Wild coffee species, notably those growthing in highly constrained environments in Madagascar, offer a critical genetic resource to address these challenges. Understanding adaptive traits allowing these species to establish into arid environments is essential to implement guid breeding strategies into create resilient coffee varieties. Here, we hypothesize that these wild Coffee species display unique traits compared to other Coffea species, reflecting adaptations to arid and seasonally dry environments. We used the architectural analysis to describe three Baracoffea species and compare them to known cultivated Coffee.Field studies were conducted in two contrasting sites in Madagascar, focusing on three wild coffee species, natively growing into arid environments: Coffea ambongensis, C. bissetiae, and C. boinensis. Structural traits at the whole plant scale were measured across developmental stages using morphological and architectural analyses.Our results suggest that unique traits characterize Barracoffea species, such as rhythmic growth, terminal flowering on short shoots, and species-specific developmental strategies. These findings highlight the architectural diversity of Baracoffea, identify potential key drivers of ecological adaptation and therefore highlights the potential of this group of species for breeding climate- resilient coffee varieties.
An updated proteomic analysis ofDrosophilahemolymph after bacterial infection
Authors: Rommelaere Samuel , Schüpfer Fanny , Armand Florence , Hamelin Romain , Lemaitre Bruno 
Published: January 2025

AbstractUsing an in-depth Mass Spectrometry based proteomics approach, we provide a comprehensivecharacterization of the hemolymphatic proteome of adult flies upon bacterial infection. We detected and quantified changes in abundance of several known immune regulators and effectors, including multiple antimicrobial peptides, peptidoglycan-binding proteins and serine proteases. Comparison to previously published transcriptomic analyses reveals a partial overlap with our dataset, indicating that many proteins released into the hemolymph upon infection may not be regulated at the transcript level. Among them, we identify a set of muscle-derived proteins released into the hemolymph upon infection. Finally, our analysis reveals that infection induces major changes in the abundance of proteins associated with mitochondrial respiration. This study uncovers a large number of previously undescribed proteins potentially involved in the immune response.
Negative selection on baboon admixture is strongest on chromosome X
Authors: Sørensen Erik F. , Hellenthal Garrett , Munch Kasper 
Published: January 2025

AbstractThe six admixing baboon species offer a natural experiment to study negative selection on admixture and potentially genetic incompatibility in species with divergence resembling that between anatomically modern and extinct human subspecies such as Neanderthals. We analyze 156 high-coverage genomes sampled from seven olive and four yellow baboon populations shaped by admixture in two different reticulation events. In Tanzania, olive and yellow baboons admix despite 1.3 million years of divergence. In Ethiopia, olive baboons have invaded and displaced an ancient Hamadryas-like population separated by 0.6 million years, thus mirroring the displacement of Neanderthals by modern humans. Analyzing local ancestry across whole genome, we find evidence of negative selection on minor parent ancestry in Tanzanian yellow and olive baboon populations reaching far behind the hybrid zone and in Ethiopian olive baboons. We find that evidence of selection against admixture is up to seven times stronger on the X chromosome. The proportion of minor parent ancestry is substantially higher on the X chromosome in Ethiopian olive and yellow baboon populations, which displaced the populations now representing their minor parent ancestry. This additional MPA is concentrated in a few genomic regions with high frequency. This indicates that this original ancestry was retained by negative selection on the invading ancestry, suggesting that these loci play a role in emerging reproductive barriers in the Papio as well as the Homo genus.
Identification of ketotic cattle based on milk spectroscopic characteristics: a chemometric modelling approach built upon the principles of Aquaphotomics
Authors: Giovinazzo Simone , Bisaglia Carlo , Cattaneo Tiziana M.P. , Marinoni Laura , Cabassi Giovanni , Brambilla Massimo 
Published: January 2025

AbstractThe early diagnosis of metabolic disorders in intensive farms, such as ketosis, allows a timely health treatment, resulting in improved animal welfare and reduced productivity and economic losses for farmers. This approach represents an opportunity for more sustainable animal production practices.For these reasons, we developed a chemometric processing model based on GNU Octave capable of identifying milk sample categories based on the chemo-physical characteristics of their near-infrared signature. Such a characterisation relies on the innovative approach of aquaphotomics, which investigates the interaction between light and water molecules in any biological system. Aquaphotomics leverages the properties of water as a biomarker and amplifier to identify changes in the system indicative of a perturbation, such as the onset of a metabolic disorder.The realised package allows spectral data elaborations, including preprocessing methods like the calculation of spectrum derivatives, noise removal and scatter correction techniques, as well as chemometric analysis like Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), and Partial Least Squares Regression (PLSR). In this way, the code enables the identification of the most significant water bands implicated in the origin of the disease, with the potential to represent an innovative approach for monitoring the health status of animals.
Integration of spatial and single nucleus transcriptomics to map gene expression in the developing mouse kidney
Authors: Chaney Christopher P. , Fusco Alexandria N. , Grilli Elyse D. , Warshaw Jane N. , Luo Peter M. , Cleaver Ondine , Marciano Denise K. , Carroll Thomas J. 
Published: January 2025

SummaryThe kidney is a complex organ requiring tightly coordinated interactions between epithelial, endothelial, and mesenchymal cells during development. Congenital kidney defects can result in kidney disease and renal failure, highlighting the importance of understanding kidney formation mechanisms. Advances in RNA sequencing have revealed remarkable cellular heterogeneity, especially in the kidney stroma, though relationships between stromal, epithelial, and endothelial cells remain unclear.This study presents a comprehensive gene expression atlas of embryonic and postnatal kidneys, integrating single-nucleus and in situ RNA sequencing data. We developed the Kidney Spatial Transcriptome Analysis Tool (KSTAT), enabling researchers to identify cell locations, predict cell-cell communication, and map gene pathway activity. KSTAT revealed significant heterogeneity among embryonic kidney pericytes, providing a critical resource for hypothesis generation and advancing knowledge of kidney development and disease.
Regulation of epigenetics and chromosome structure by human ORC2
Authors: Su Zhangli , Tian Mengxue , Shibata Etsuko , Shibata Yoshiyuki , Yang Tianyi , Wang Zhenjia , Jin Fulai , Zang Chongzhi , Dutta Anindya 
Published: January 2025

ABSTRACTThe six subunit Origin Recognition Complex (ORC) is a DNA replication initiator that also promotes heterochromatinization in some species. A multi-omics study in a human cell line with mutations in three subunits of ORC, reveals that the subunits bind to DNA independent of each other rather than as part of a common six-subunit ORC. While DNA-bound ORC2 was seen to compact chromatin and attract repressive histone marks, the activation of chromatin and protection from repressive marks was seen at a large number of sites. The epigenetic changes regulate hundreds of genes, including some epigenetic regulators, adding an indirect mechanism by which ORC2 regulates epigenetics without local binding. DNA-bound ORC2 also prevents the acquisition of CTCF at focal sites in the genome to regulate chromatin loops. Thus, individual ORC subunits are major regulators, in both directions, of epigenetics, gene expression and chromosome structure, independent of the role of ORC in replication.
Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing
Authors: Yanagi Tomoki , Phen Shean Fu , Ayala Jonah , Aydin Deniz Ece , Truong David M. 
Published: January 2025

AbstractInducible gene expression circuits offer precise control over target gene activation, making them essential tools for direct reprogramming, where cells are guided to differentiate into specific cell types. However, stable circuit function and consistent expression of key inducible proteins are crucial for effective reprogramming, and DNA methylation-induced silencing hinders this stability. To address this issue, A2-ubiquitous chromatin opening elements (A2UCOE) have gained attention for their ability to maintain open chromatin and prevent methylation, thereby stabilizing gene expression. In this study, we aimed to forward program iPSCs into thymic epithelial cells (TECs) using a compact, all-in-one gene circuit composed of a doxycycline-inducible Tet-On system, 863-bp A2UCOE (0.9 UCOE), andFOXN1, a master transcription factor for TEC differentiation. This compact construct enables site-specific genome integration and stable inducible expression within iPSCs for renewably generating TECs. While the 0.9 UCOE promoted stable expression of constitutively expressed genes, it also caused unintendedFOXN1gene leakage, leading to unprogrammed gradual differentiation of the iPSCs. We generated A2UCOE fragments of varying lengths and found that gene leakage persisted regardless of fragment size. We tested spacer sequences between the A2UCOE and the Tet-On promoter consisting of varying AT-nucleotide content (35, 50, and 65%) and the 65% AT-rich SV40 poly-A terminator sequence and found that only the SV40 poly-A mitigated this leakage, and surprisingly, enhanced desired anti-silencing effects. These findings highlight the benefits and potential risks of using A2UCOE in iPSCs, and provides insights into a regulatory DNA architecture optimal for compact forward programming circuits for controlled iPSC differentiation.Graphical abstract
Cross-site imputation for recovering variables without individual pooled data
Authors: Thiesmeier Robert , Madley-Dowd Paul , Orsini Nicola , Ahlqvist Viktor H. 
Published: January 2025

AbstractIn multi-site studies, it is common for some sites not to have recorded key variables. Although it is theoretically possible to use data from sites with recorded observations to impute the missing values, this process becomes challenging when data pooling is not feasible due to logistic or legal constraints. We therefore propose a multiple imputation approach — cross-site imputation — to recover any variables across sites without the need to pool individual-level data. The solution involves transporting predicted regression coefficients and variances from studies with observed data to impute missing variables at sites without data. The approach is illustrated in an applied example of recovering confounders across Swedish hospitals, and theoretical considerations are outlined. Given the increasing importance of multi-site studies in observational research, cross-site imputation could offer a practical approach for imputing variables that have not been recorded in some study sites.