bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excavating Podocyte-Protective Targets of phloroglucinol-terpene hybrids Utilizing AI Models and Omics Analysis
Authors: Chen Ting , Liu Xiaoyan , Zhu Juan , Zhang Xinting , Zhang Jianhui , Yu Hongping , Xu Ziyan , Wang Dingyan , Zhu Yaobin , Zhong Feisheng , Luo Jiewei 
Published: February 2025

AbstractLupus nephritis (LN) is a multifactorial autoimmune inflammatory disorder, with podocyte dysfunction or structural abnormalities playing a pivotal role in its pathogenesis.Eucalyptusleaves, traditionally employed in folk medicine, have demonstrated notable efficacy in managing non-infectious inflammations. Eucarbwenstols D (R14) is a novel phloroglucinol-terpene that has been isolated fromEucalyptus robusta. To further refine potential targets, we utilized an AI scoring system and successfully identified the epidermal growth factor receptor (EGFR) as the novel target of R14. This discovery was built upon the foundation of transcriptome and connectivity mapping (CMap) analysis. Molecular docking and molecular dynamics simulations were employed to analyze the interaction between R14 and EGFR, surface plasmon resonance (SPR) and homogeneous time-resolved fluorescence (HTRF) assays were utilized to accurately quantify the binding affinity between R14 and EGFR. Western blot (WB) and immunofluorescence assays were then conducted to explore the downstream signaling pathways initiated by EGFR, specifically the PI3K/AKT/mTOR pathway. These assays demonstrated that R14 modulates the expression of apoptotic proteins Bax and Bcl-2 through this pathway, thereby exerting a protective effect on podocytes from undergoing apoptosis. The modulation of key podocyte proteins, nephrin and podocin, further substantiates this protective effect. Overall, we have applied a novel AI algorithm model that transcends bioinformatics analysis to precise identification of the novel podocyte target of R14. In this study, R14 was identified for the first time as a novel scaffold compound for EGFR inhibition. Moreover, R14 has demonstrated its capacity to inhibit podocyte apoptosis, thereby protecting these critical cells. This discovery establishes a robust theoretical foundation for the use of phloroglucinol-terpene hybrids (PTHs) in the treatment of LN.
Meltome Atlas ofArabidopsis thalianaProteome: A Melting Temperature-Based Identification of Heat & Cold Resistant Proteins
Authors: Mohanta Karan Martens , Mohanta Tapan Kumar 
Published: February 2025

AbstractThe study elucidated the thermal properties of the entireArabidopsis thalianaproteome by considering the melting temperature (Tm) and the melting temperature index (TI). In total, 48359 protein sequences were analyzed, and the melting temperature of the proteins was recorded in three groups (Tm < 55°C, 55-65°C, and > 65°C). The Tm index of theA. thalianaproteome ranged from -15.6008 (< 55°C) to 9.605 (> 65°C). At least 22826 proteins were found in the Tm group of 55°C to 65°C, 20640 proteins were found in the Tm group of > 65°C, and only 4893 proteins were found in the Tm group of < 55°C. The mediator of RNA polymerase II transcription subunit-like protein was found to possess the highest Tm index (9.60), while the NADH dehydrogenase 5B subunit was found to contain the lowest TI (-15.60). The amino acid composition analysis of theA. thalianaproteome revealed that the frequency of Ala, Asp, Glu, Gly, Lys, Gln, and Val increased with the increase in Tm, while the amino acids Cys, Phe, and Trp decreased with the increase in the Tm of theA. thalianaproteome. The molecular mass of theA. thalianaproteome ranged from 0.149 to 611.888 kDa, and protein in the Tm group at 55-65°C showed the highest average molecular mass. The machine learning analysis revealed an increase in the molecular mass positively correlated with the increase in the Tm of the proteins. The codon usage pattern revealed, the codon pair prefer the Tm group specific occurrence where ATG-ATG, CAA-CAA codon pairs were predominated. Relative synonymous codon usage of the three Tm groups revealed AGA (Arg) and CCA (Pro) were the preferred codons for the low and high Tm group DNA sequences, respectively. Codon context analysis revealed the presence of preferences of the Tm group specific codon pairing. There was a variation in the nucleotide position of the codons in different Tm groups. Evolutionary study revealed, gene duplication was the predominant evolutionary feature and all of the studied genes in the three Tm group undergone duplication. Codon context analysis revealed distinct clustering pattern in high Tm protein group. The study underscores the role of amino acid composition, molecular mass, and codon usage in determining the thermal stability of the proteins in theA. thaliana. The study reflected the evolution of high Tm-adapting genes through gene duplication, highlighting the role of gene and genome evolution towards encoding high Tm proteins for stress resilience.
Computational modeling of human genetic variants in mice
Authors: Dong Kexin , Gould Samuel I. , Li Minghang , Sánchez Rivera Francisco J. 
Published: February 2025

AbstractMouse models represent a powerful platform to study genes and variants associated with human diseases. While genome editing technologies have increased the rate and precision of model development, predicting and installing specific types of mutations in mice that mimic the native human genetic context is complicated. Computational tools can identify and align orthologous wild-type genetic sequences from different species; however, predictive modeling and engineering of equivalent mouse variants that mirror the nucleotide and/or polypeptide change effects of human variants remains challenging. Here, we present H2M (human-to-mouse), a computational pipeline to analyze human genetic variation data to systematically model and predict the functional consequences of equivalent mouse variants. We show that H2M can integrate mouse-to-human and paralog-to-paralog variant mapping analyses with precision genome editing pipelines to devise strategies tailored to model specific variants in mice. We leveraged these analyses to establish a database containing > 3 million human-mouse equivalent mutation pairs, as well asin silico-designed base and prime editing libraries to engineer 4,944 recurrent variant pairs. Using H2M, we also found that predicted pathogenicity and immunogenicity scores were highly correlated between human-mouse variant pairs, suggesting that variants with similar sequence change effects may also exhibit broad interspecies functional conservation. Overall, H2M fills a gap in the field by establishing a robust and versatile computational framework to identify and model homologous variants across species while providing key experimental resources to augment functional genetics and precision medicine applications. The H2M database (including software package and documentation) can be accessed athttps://human2mouse.com.
Interactive effect ofMoringa oleiferamediated green nanoparticles and arbuscular mycorrhizal fungi on growth, root system architecture, and nutrient uptake in maize (Zea maysL.)
Authors: Ain Qurat ul , Hussain Hafiz Athar , Rahman Lutfur , Zhang Qingwen , Rehman Asma , Hussain Saddam , Uddin Saleem , Imran Asma 
Published: February 2025

AbstractThe synergistic interaction between green nanoparticles (NPs) and mycorrhizal fungi promotes plant growth by improving nutrient absorption, optimizing root function, and stress resistance. In this study, we explored the impact of arbuscular mycorrhizal fungus (AMF)Funnaliformis mosseaeandMoringa oleiferamediated green NPs viz; iron oxide (FeO), zinc oxide (ZnO), and Zn doped FeO (Zn/Fe) NPs, both individually and in combination, on maize growth, root system architecture, organic acids production, mycorrhizal colonization, and nutrients uptake. Prior to NP synthesis, metabolomic analysis ofMoringa oleiferaleaves was conducted to characterize its bioactive compounds. The structural properties of green synthesized NPs confirmed by characterization using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectrophotometry, and X-ray diffraction (XRD). The results showed that all individual and combined treatments of AMF and green NPs significantly enhanced maize growth compared to the control. Among the single NP treatments, Zn/Fe NPs exhibited superior performance over FeO and ZnO. However, when combined with AMF, ZnO and Zn/Fe NPs induced the highest growth responses than FeO NPs. The ZnO NPs proved most compatibility with AMF for improving colonization in maize roots, whereas FeO and Zn/Fe NPs reduced colonization efficiency. Furthermore, combination of AMF and ZnO NPs (AMF+ ZnO) noted as most prominent treatment for improvement of maize growth compared to other all treatments, highlighting the potential of AMF+ ZnO NPs for sustainable agricultural applications.
The pulvinar regulates plasticity in human visual cortex
Authors: Acquafredda Miriam , Kurzawski Jan W. , Biagi Laura , Tosetti Michela , Morrone Maria Concetta , Binda Paola 
Published: February 2025

AbstractIn normally sighted human adults, two-hours of monocular deprivation is sufficient to transiently alter ocular dominance. Here we show that this is associated with a reduction of functional connectivity between the pulvinar and early visual cortex, selective for the pulvinar-to-V1 directionality. Our results support a revised model of adult V1 plasticity, where short-term reorganization is gated by modulatory signals relayed by the pulvinar.
Genome-wide profiling of tRNA modifications reveal the presence of divergent signatures inPlasmodium falciparum
Authors: Li Qian , Veith Ylva , Christ Elena , Ankarklev Johan , Larsson Ola , Chan Sherwin Chun-Leung 
Published: February 2025

AbstracttRNAs are known to be extensively decorated with various nucleotide modifications, which can modulate the biological properties of tRNAs, such as promoting translation efficiency or fidelity, influencing codon preference and stabilizing tertiary structure of tRNAs. Dynamic alteration of the tRNA modifications, particularly under stress, are conserved gene regulatory mechanisms employed by cells across the kingdoms of life. The malaria-causingPlasmodium falciparum, which has a highly AT-biased genome, is reliant on a non-redundant set of tRNA genes to decode distinct and codon-skewed transcriptomes across its developmental stages. This genomic feature highlights the regulatory potential of tRNA modifications and warrants studies on how the tRNA epitranscriptome can impact gene regulatory function in this parasite. However, systematic studies of tRNA modifications inP. falciparumremain sporadic. In this study, we present a sequencing-based analysis of tRNA modifications inP. falciparumthrough optimizing the TGIRT-tRNA sequencing approach. The optimized protocol significantly reduces reverse transcription (RT) stop-induced short reads and enhances full-length cDNA synthesis, enabling the identification and stoichiometric estimation of a select nucleotide modifications at single-base resolution. We were able to identify seven types of conserved tRNA modifications and discovered two non-canonical signatures at A59 and U73 positions on specific nuclear-encoded tRNAs, which provides new insights into previously unreported modification sites. Our findings further reveal the dynamic nature of tRNA modifications during stage progression and under stress conditions.
PLXNB1 and other signaling drives a pathologic astrocyte state contributing to cognitive decline in Alzheimer’s Disease
Authors: Comandante-Lou Natacha , Lama Tsering , Chen Kevin , Zhang Jinglong , Hu Bin , Liu Shuhui , Heuer Sarah , Brennand Kristen J. , Schneider Julie , Barnes Lisa , Zhang Bin , Wang Minghui , Zou Hongyan , Friedel Roland H. , Ma Yiyi , Young-Pearse Tracy , Li Aiqun , Fujita Masashi , Bennett David , Zhang Ya , Menon Vilas , Klein Hans-Ulrich , Taga Mariko , De Jager Philip L. 
Published: February 2025

AbstractAlzheimer’s disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple cell types. Here, we first performed a meta-analysis of single-nucleus transcriptomic (snRNAseq) data from 869 brains of diverse decedents, confirming the critical role of anSLC38A2highSMTNhighCACNA1Dhighastrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated the signaling drivers of Ast10’s emergence in the aging brain, focusing on interactions among microglial and astrocytic subsets. Analysis of the snRNAseq data prioritized a set of ligands and receptors that are robustly predictive of Ast10 proportions across participants, and we confirm our predictions in multiple studies. Independent validation with spatial transcriptomics reveals striking colocalization of these prioritized ligands with the Ast10 signature in AD brain tissue, but not with other astrocytic states. Genetic ablation of a top receptorPLXNB1in murine and human iPSC-derived astrocytes decreased the Ast10 signature, confirming its regulatory role. Finally, we find that Ast10 may contribute to cognitive decline through synaptic loss and is associated with cognitive decline independent of AD. Thus, Ast10 and its regulators are potential points of convergence for multiple neurodegenerative mechanisms and may be promising targets for therapeutic development to preserve cognitive function.
Neurons exploit stochastic growth to rapidly and economically build dense radially oriented dendritic arbors
Authors: Ouyang Xiaoyi , Sutradhar Sabyasachi , Trottier Olivier , Shree Sonal , Yu Qiwei , Tu Yuhai , Howard Jonathon 
Published: February 2025

AbstractDendrites grow by stochastic branching, elongation, and retraction. A key question is whether such a mechanism is sufficient to form highly branched dendritic morphologies. Alternatively, are signals from other cells or is the topological hierarchy of the growing network necessary for dendrite geometry? To answer these questions, we developed a mean-field model in which branch dynamics is isotropic and homogenous (i.e., no extrinsic instruction) and depends only on the average lengths and densities of branches. Branching is modeled as density-dependent nucleation so there are no tree structures and no network topology. Despite its simplicity, the model predicted several key morphological properties of class IV Drosophila sensory dendrites, including the exponential distribution of branch lengths, the parabolic scaling between dendrite number and length densities, the tight spacing of the dendritic meshwork (which required minimal total branch length), and the radial orientation of branches. Stochastic growth also accelerated the overall expansion rate of the arbor. Therefore, stochastic dynamics is an economical and rapid space-filling mechanism for building dendritic arbors without external guidance or hierarchical branching mechanisms. Our model provides a general theoretical framework for understanding how macroscopic branching patterns emerge from microscopic dynamics.
Generative model for the first cell fate bifurcation in mammalian development
Authors: Avdeeva Maria , Chalifoux Madeleine , Joyce Bradley , Shvartsman Stanislav Y. , Posfai Eszter 
Published: February 2025

AbstractThe first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asyn-chronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, key transcription factors of TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate bifurcations in mouse development.
Sex-differences in catecholamine transporter expression in the rodent prefrontal cortex following repetitive mild traumatic brain injury and methylphenidate treatment
Authors: Papadopoulos Eleni , Abrimian Anna , Knapp Christopher P. , Loweth Jessica A. , Waterhouse Barry D. , Navarra Rachel L. 
Published: February 2025

AbstractIrregular catecholamine transmitter activity is theorized to underly impaired prefrontal cortex (PFC)-mediated executive functions following repetitive mild traumatic brain injury (rmTBI). The psychostimulant, methylphenidate (MPH), enhances catecholamine neurotransmission by blocking reuptake transporters and is used off-label to treat post-TBI executive dysfunction. Although rmTBI and MPH have been shown to independently alter catecholamine transporter levels, the present report evaluated the interactive effects of rmTBI and a sub-chronic therapeutic dose of MPH on expression levels of vesicular monoamine transporter-2 (VMAT2) and norepinephrine reuptake transporter (NET) within subregions of the PFC in both male and female rats. Treatment with MPH restored rmTBI-induced reductions in transporter expression in females. However, in males subjected to rmTBI, MPH exacerbated reductions in transporter expression within the PFC. These results suggest MPH treatment produces beneficial effects in females but exaggerates pathological outcomes in males when used to treat post-rmTBI symptoms.
A Structured, Collaborative and Open Access Database of Food Policies in Europe: Introducing EU F‐POD
Authors: Benedetti Elena , Biondi Beatrice , De Nicolò Silvia , Mazzocchi Mario 
Published: February 2025

SummaryThis paper presents a new, open‐access database of food policies, the European Food Policy Database (EU F‐POD). It is a comprehensive and collaborative on‐line resource, and goes beyond a mere list of food policies by offering a structured collection of food policies classified by goals, targets, and instruments, drawing from existing and validated taxonomies. It consists of an organized and cohesive body of national and international laws, regulations, and provisions related to the food area, to facilitate consultation, interpretation and policy analysis. More specifically, it may help identify normative gaps, contradictions or overlaps between existing rules, and regulatory differences between states, fostering discussions among various multi‐sectoral actors. The EU F‐POD database is comprehensive in scope, ensuring the inclusion of policies for all objectives, targets, and instruments within its framework. We describe the EU F‐POD database, its structure, definition, and data collection strategy, including also some extraction examples to demonstrate the potential of such a tool to users. EU F‐POD was designed as an open access tool, so that a supervised, collaborative effort among researchers and experts can guarantee its future sustainability and updating.
Behaviors in the Slaughter Corridor, Carcass, and Meat Quality Traits of Anatolian, Italian, and Italian × Anatolian Crossbreds (F1) Water Buffaloes
Authors: Özdemir Seyfi , Kecici P. Dilara , Yalcintan Hulya , Ekiz Bulent 
Published: February 2025

ABSTRACTThis study aimed to assess the slaughter corridor behavior, carcass characteristics, and meat quality of Anatolian, Italian, and Italian × Anatolian (F1) crossbred water buffaloes. The research involved Anatolian (n = 8), Italian (n = 10), and Italian × Anatolian crossbred (n = 8) water buffaloes, all of which had been used for milk production on a commercial farm before being culled and slaughtered. While water buffalo pass through the slaughter corridor, both the behaviors of the animals and the handling actions of the stockpersons were video recorded. Genotype had no significant influence on the scores for animal behaviors (AWBEH) and stockperson actions (AWACT). There were significant differences in carcass weight among the genotypes (p < 0.001), with the genotypes ranked from smallest to largest in carcass weight as follows: Anatolian, crossbred (F1), and Italian water buffaloes. Additionally, the EUROP fatness score was higher in carcasses from the Italian genotype compared to the Anatolian water buffaloes. Mean pH24h was lower in Italian water buffaloes than Anatolian ones. On the other hand, fat and meat color variables were not influenced by animal genotype. In conclusion, crossbreeding between Italian and Anatolian water buffaloes may increase carcass weight in crossbred (F1) genotype without altering meat quality or temperament.
Integrating data to assess occupancy patterns of an endangered bumble bee
Authors: Ellis Kristen S. , Otto Clint R. V. , Bailey Larissa L. , Smith Tamara A. , Choy Steven , Hatch Lauren 
Published: February 2025

AbstractThere is growing interest in integrating community science data with structured monitoring data to estimate changes in distribution patterns of imperiled species, including pollinators. However, significant challenges remain in determining how unstructured community science data should be incorporated into formal analyses of species distributions. We developed a dynamic framework for combining community science and structured monitoring data of bumble bees to estimate changes in occupancy of rusty‐patched bumble bees (Bombus affinis), a federally endangered species in the United States. We applied traditional metapopulation theory and accounted for imperfect detection to estimate site‐specific extirpation risk and colonization rates across the known distribution of B. affinis in the Upper Midwest (USA). Despite a 144% increase in presence‐only detections from 2017 to 2022, occupancy probabilities and the estimated number of occupied sites remained static or declined slightly across a 4‐state region during this period. Our results provide preliminary evidence that the probability of local extirpation risk of B. affinis increased in response to drought, but that effect was tempered with a high number of neighboring patches occupied by B. affinis (i.e., rescue effect). Our framework can be used by managers to track population recovery goals for B. affinis and other bumble bees of conservation concern. In addition, our study highlights the importance of accounting for imperfect detection and addressing spatial sampling biases in bumble bee monitoring efforts, particularly those for which a portion of the monitoring data are generated from community science projects.