bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genetic Analysis of Lipid Metabolism Regulation in Han Chinese Youth in Xinjiang via Extreme Phenotypic Strategies
Authors: Yu Jiaqing , Ma Yitong 
Published: February 2025

AbstractThe Xinjiang Uyghur Autonomous Region of the People’s Republic of China has been influenced by its natural ecological environment, historical evolution, and cultural customs since ancient times. The aim of this study was to investigate new genes that contribute to lipid metabolism regulation in Han Chinese youth in the Xinjiang region through sequencing analysis. Based on the threshold value of triglycerides (TG), we selected two groups of Han Chinese university students, namely, individuals with extremely low TG levels and individuals with normal TG levels, and conducted whole-exome sequencing on samples from these individuals. Ten genes (ACTN2, DHTKD1, NLRP9, PTPRA, INPP4B, PHGDH, PYROXD2, RIN1, MYRIP, and PRSS57) were selected via bioinformatics analysis of the sequencing results. Subsequently, we can conduct further validation at the cellular and animal levels to screen for emerging genes associated with lipid metabolism.
ABL Kinases Modulate EZH2 Phosphorylation and Signaling in Metastatic Triple Negative Breast Cancer
Authors: Colemon Ashley , Prioleau Tatiana , Rouse Clay , Pendergast Ann Marie 
Published: February 2025

AbstractTriple-negative breast cancer (TNBC) remains a leading cause of cancer associated deaths in women owing to its highly metastatic potential and limited treatment options. Recent studies have shown that expression of proteins associated with epigenetic regulation of gene expression are associated with metastatic relapse, however targeting epigenetic regulatory proteins has not resulted in effective therapies for TNBC in the clinic. The ABL tyrosine kinases promote metastasis of breast cancer cells in mouse models. However, a role of ABL kinases in the regulation of epigenetic processes in solid tumor metastasis remains unexplored. Here we show that inactivation of ABL kinases in bone metastatic TNBC cells led to a significant enrichment in gene signatures associated with the PRC2 protein complex, revealing a functional link between ABL kinases and the PRC2 complex. ABL inactivation promotes EZH2-T487 phosphorylation through the regulation of a FAK-CDK1 signaling axis. We find that phosphorylated EZH2 T487 or a phosphomimic EZH2 T487D mutant exhibit increased binding to non-canonical binding partners of EZH2 including c-MYC and ZMYND8. Notably, we identify a therapeutic vulnerability in TNBC cells whereby combination treatment with ABL allosteric inhibitors and EZH2 inhibitors elicits a synergistic decrease in TNBC cell survival in vitro, and impairs TNBC metastasis, prolonging survival of tumor-bearing mice treated with the combination therapy.One Sentence SummaryABL Kinases indirectly impact EZH2 catalytic activity by blocking a signaling cascade that leads to changes in the phosphorylation, protein interactions, and function of the PRC2 catalytic component EZH2 in TNBC.
Comparative Transcriptomic Analysis of Perfluoroalkyl Substances-Induced Responses of Exponential and Stationary PhaseEscherichia coli
Authors: Wintenberg Molly E. , Vasilyeva Olga B. , Schaffter Samuel W. 
Published: February 2025

ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are highly stable chemical contaminants of emerging concern for human and environmental health due to their non-natural chemistry, widespread use, and environmental persistence. Despite conventional metrology, mitigation strategies, and removal technologies, the complexity of this growing problem necessitates the need for alternative approaches to tackle the immense challenges associated with complex environmental PFAS contamination. Recently, biology has emerged as an alternative approach to detect and mitigate PFAS and understand the molecular-level responses of living organisms, including microorganisms, to these compounds. However, further study is needed to understand how microorganisms in different environments and growth phases respond to PFAS. In this study, we performed RNA sequencing at mid-exponential, early stationary phase, and late stationary phase of bacterial growth to determine the global transcriptional response of a model chassis,Escherichia coliMG1655, induced by two PFAS, perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA), and equivalent non-fluorinated carboxylic acids (NFCA), octanoic acid and dodecanoic acid. Differential gene expression analysis revealed PFOA and PFDoA induced distinct changes in gene expression throughout cultivation. Specifically, we identified significant changes in expression of the formate regulon and sulfate assimilation at mid-exponential phase and ferrous iron transport, central metabolism, the molecular chaperone network, and motility processes during stationary phase. Importantly, many of these changes are not induced by NFCAs. In summary, we found PFAS induced a system-level change in gene expression, and our results expand the understanding of bacterial-PFAS interactions that could enable the development of future real-time environmental monitoring and mitigation technologies.ImportanceThe prevalence and persistence of PFAS in the environment is a growing area of concern. However, little is understood of the impacts of PFAS on the environment, particularly impacts on microorganisms that play pivotal roles in nearly every ecosystem. Thus, comprehensive measurements that provide systems-level insight into how microorganisms respond and adapt to PFAS in the environment are paramount. Here, we use RNA sequencing to study the global transcriptional response ofE. coliMG1655 to two PFAS and non-fluorinated equivalent compounds across growth phases. We find that PFAS induce system-level changes in metabolic, transport, and gene regulatory pathways, providing insight into how these non-natural chemicals interact with a model bacterium. Additionally, the transcriptomic dataset associated with this work provides the community with PFSA-specific gene expression patterns and possible PFAS degradation pathways for the development of future whole-cell biosensors and mitigation efforts.
The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control
Authors: McCaffrey Erin F. , Delmastro Alea C. , Fitzhugh Isobel , Ranek Jolene S. , Douglas Sarah , Peters Joshua M. , Fullaway Christine Camacho , Bosse Marc , Liu Candace C. , Gillen Craig , Greenwald Noah F. , Anzick Sarah , Martens Craig , Winfree Seth , Bai Yunhao , Sowers Cameron , Goldston Mako , Kong Alex , Boonrat Potchara , Bigbee Carolyn L. , Venugopalan Roopa , Maiello Pauline , Klein Edwin , Rodgers Mark A. , Scanga Charles A. , Lin Philana Ling , Kirschner Denise , Fortune Sarah , Bryson Bryan D. , Butler J. Russell , Mattila Joshua T. , Flynn JoAnne L. , Angelo Michael 
Published: February 2025

SUMMARYDespite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response toMycobacterium tuberculosis(Mtb) infection and support bacterial persistence. We previously discovered that human TB granulomas are enriched for immunosuppressive factors typically associated with tumor-immune evasion, raising the intriguing possibility that they promote tolerance to infection. In this study, our goal was to identify the prime drivers for establishing this tolerogenic niche and to determine if the magnitude of this response correlates with bacterial persistence. To do this, we conducted a multimodal spatial analysis of 52 granulomas from 16 non-human primates (NHP) who were infected with low dose Mtb for 9-12 weeks. Notably, each granuloma’s bacterial burden was individually quantified allowing us to directly ask how granuloma spatial structure and function relate to infection control. We found that a universal feature of TB granulomas was partitioning of the myeloid core into two distinct metabolic environments, one of which is hypoxic. This hypoxic environment associated with pathologic immune cell states, dysfunctional cellular organization of the granuloma, and a near-complete blockade of lymphocyte infiltration that would be required for a successful host response. The extent of these hypoxia-associated features correlated with worsened bacterial burden. We conclude that hypoxia governs immune cell state and organization within granulomas and is a potent driver of subverted immunity during TB.
A complete mitochondrial genome-based phylogeny of gooseneck barnacles confirms the sister group relationship between the easternPacific Pollicipeselegans and the eastern AtlanticP. pollicipes
Authors: Alfaro Ruben , Mantilla Guillermo , Marín Alan 
Published: February 2025

AbstractBackgroundGooseneck barnacles are a fascinating invertebrate group and their taxonomic classification has attracted the attention of several specialists, including Charles Darwin, who was the first to note the close relationship between two species of gooseneck barnacles found on the eastern coasts of the Pacific,Pollicipes elegans, and the Atlantic,P. pollicipes. Additionally, a third species from the eastern Pacific,P. polymerus, was believed to have diverged earlier from the group.Methods and resultsHere, we used genomic short-read sequences publicly available in GenBank to assemble the first complete mitochondrial genome ofP. elegans. We conducted a phylogenetic analysis to assess the relationships among its related species and other cirripede species from the superorder Thoracicalcarea. Our phylogenetic findings based on complete mitogenomes reinforce the close relationship betweenP. elegansandP. pollicipes, withP. polymerusemerging as a basal branch, indicating an earlier divergence from the group.ConclusionsOur analysis provided the first robust phylogenetic assessment ofP. elegans, strongly supporting its close relationship withP. pollicipes. Further efforts should aim to sequence the complete mitogenomes of other species within the order Pollicipedomorpha. This endeavor will enable a more comprehensive phylogenetic analysis of this group, whose classification remains a subject of debate.
Growth vs. Diversity: A Time-Evolution Analysis of the Chemical Space
Authors: Perez Kenneth Lopez , López-López Edgar , Soulage Flavie , Felix Eloy , Medina-Franco José L. , Miranda-Quintana Ramon Alain 
Published: February 2025

AbstractChemical space is a core and theoretical concept in cheminformatics, and it also has practical applications in drug discovery and other research areas. Chemical space is frequently associated with the number of molecules in the universe (e.g., chemical universe). It is well known that the number of compounds (both synthesized and theoretical ones) is rapidly increasing. It would be obvious to affirm that the chemical space is expanding (as a proxy of growth). But is the chemical diversity of compound libraries growing? In this study, we tackle this question by assessing quantitatively the time evolution of chemical libraries in terms of the chemical diversity as measured with molecular fingerprints. To tackle this task, we employed innovative cheminformatics methods to assess the progress over time of the chemical diversity of compound libraries available in the public domain. Using the iSIM and the BitBIRCH clustering algorithm, we conclude that, based on the fingerprints used to represent the chemical structures, just an increasing number of molecules cannot be directly translated to diversity for the analyzed libraries. With these tools, we have identified what releases contributed to the diversity of the library and the zones it did.
Lack of motor defects and ALS-like neuropathology in heterozygousSptlc1Exon 2 deletion mice
Authors: Pant Devesh C. , Lone Museer A. , Parameswaran Janani , Ma Fuying , Dutta Prisha , Wang Zitong , Park Jaekeun , Verma Sumit , Hornemann Thorsten , Jiang Jie 
Published: February 2025

AbstractMutations in the humanSPTLC1gene have recently been linked to early onset amyotrophic lateral sclerosis (ALS), characterized by global atrophy, motor impairments, and symptoms such as tongue fasciculations. All known ALS-linkedSPTLC1mutations cluster within exon 2 and a specific variant, c.58G>T, results in exon 2 skipping. However, it is unclear how the exon 2 deletion affects SPTLC1 functionin vivoand contributes to ALS pathogenesis. Leveraging the high genomic sequence similarity between mouse and humanSPTLC1, we created a novel mouse model with a CRISPR/Cas9-mediated deletion of exon 2 in the endogenous murineSptlc1locus. While heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings indicate thatSptlc1ΔExon2 heterozygous mice do not replicate the disease phenotype but provide valuable insights into SPTLC1 biology and serve as a useful resource for future mechanistic studies.
Genome-wide mapping of 5ʹ-aldehyde terminus induced by reactive oxygen species
Authors: Wu Junzhou , Jiang Yang , Sun Jingjing , Dedon Peter C. , Sturla Shana J. 
Published: February 2025

AbstractDNA single strand breaks (SSBs) are abundant lesions due to cell metabolism and reactive oxygen species (ROS) and can lead to replication folk collapse, double strand break formation, genome rearrangements, cell death and disease. Among numerous chemical forms of SSBs, 5ʹ-aldehyde terminus are the most abundant generated by hydroxyl radicals and pose significant challenge for cellular repair machinery due to the lack of specific end processing process, potentially leading to more severe biological consequences than other readily repairable SSBs. Herein we developed a new strategy to locate 5ʹ-aldehyde terminus in genomic DNA at single-nucleotide resolution. The principle involves labelling the 5ʹ-aldehyde terminus with an aminooxy-functionalized oligonucleotide, giving rise to a biocompatible altered DNA linkage and allowing labelled sites to be amplified by polymerase chain reaction. We sequenced the 5ʹ-aldehyde terminus distribution in genomic DNA, nuclei, and cells following activation of the Fenton reaction. The results revealed a significant preference for adenine bases in DNA lesions and provided insights into the genome-wide distribution of such DNA damage, correlating with genomic features and chromatin accessibility. This method provide a new strategy for studies aiming to understand the biological and toxicological impacts of 5ʹ-aldehyde termini in DNA as the form species of single strand break induced by reactive oxygen species from a human genome.
Rapid pronucleus assembly using cytoplasmic RNAs in fertilized eggs ofXenopus laevis
Authors: Ikeda Mizuki , Tanaka Yuto , Shohoji Tatsuya , Hara Yuki 
Published: February 2025

AbstractThe size of the nucleus, which serves as the site for essential cellular functions such as replication and transcription, is dynamically altered to support these functions in response to the surrounding environment. During the brief cleavage period in metazoan embryos, the small, hypercondensed sperm nucleus with silenced chromatin undergoes a dramatic transformation into a large, round pronucleus with relaxed chromatin, enabling the activation of chromatin functions necessary for subsequent development. However, it remains unclear whether the egg cytoplasm-specific molecular environment plays a role in pronucleus assembly. In this study, we evaluated the impact of abundant RNAs in eggs on pronucleus assembly by utilizing a cell-free reconstruction of interphase nuclei inXenopus laevisegg extract. We found that when RNA levels deviated from the conventional concentration, the growth rate of the interphase nucleus decreased. Additionally, the addition of RNAs led to a more dispersed chromatin distribution and the dissociation of sperm-specific nuclear proteins from the chromatin. These chromatin remodeling properties, which were reproducible with the introduction of cationic compounds, facilitated the incorporation of somatic histones into the chromatin in reconstructed nuclei. Based on these findings, we propose that cytoplasmic RNAs promote the rapid decondensation of negatively charged chromatin from a hypercompacted state and the removal of positively charged protamines from sperm chromatin via electrical interactions. This remodeling accelerates pronucleus assembly during the brief cleavage period following fertilization and promotes the rapid growth in nucleus size.
Simultaneous immunomodulation and epithelial-to-mesenchymal transition drives lung adenocarcinoma progression
Authors: Kim Junbum , Ravichandran Hiranmayi , Yoffe Liron , Bhinder Bhavneet , Finos Kyle , Singh Arshdeep , Pua Bradley B , Bates Stewart , Huang Bevan Emma , Rendeiro Andre F. , Mittal Vivek , Altorki Nasser K. , McGraw Timothy E. , Elemento Olivier 
Published: February 2025

AbstractLung cancer remains the deadliest cancer in the United States, with lung adenocarcinoma (LUAD) as its most prevalent subtype. While computed tomography (CT)-based screening has improved early detection and enabled curative surgeries, the molecular and cellular dynamics driving early-stage LUAD progression remain poorly understood, limiting non-surgical treatment options. To address this gap, we profiled 2.24 million cells from 122 early-stage LUAD patients using multiplexed imaging mass cytometry (IMC). This analysis revealed the molecular, spatial, and temporal dynamics of LUAD development.Our findings uncover a binary progression model. LUAD advances through either inflammation, driven by a balance of cytotoxic and regulatory immune activity, or fibrosis, characterized by stromal activation. Surprisingly, tumor cell populations did not increase significantly. Instead, they displayed a mixed phenotypic profile consistent with epithelial-to-mesenchymal transition (EMT), effectively masking the expansion of malignant cells.Furthermore, we addressed discrepancies between CT-based and histology-based subtyping. CT scans, while non-invasive, often mischaracterize invasive fibrotic tumors—which account for 20.5% of LUAD cases—as mild, non-solid ground glass opacities (GGOs). Using high-content IMC imaging, we demonstrate that these tumors harbor significant risks and advocate for improved diagnostic strategies. These strategies should integrate molecular profiling to refine patient stratification and therapeutic decision-making.Altogether, our study provides a high-resolution, systems-level view of the tumor microenvironment in early-stage LUAD. We characterize key transitions in oncogenesis and propose a precision-driven framework to enhance the detection and management of aggressive disease subtypes.
Cochliobolus miyabeanusspecies-specific identification using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS)-encoding genes associated with virulence to rice
Authors: Mohd Zainudin Nur Ain Izzati , Kusai Nor Azizah , Abd Murad Nur Baiti , Wu Dongliang , Condon Bradford J. , Turgeon B. Gillian 
Published: February 2025

AbstractCochliobolus miyabeanuscauses brown spot disease of rice. For necrotrophicCochliobolusspp., some small molecule products of nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) are known pathogenicity and/or virulence factors, often acting in a host-specific manner. Previous whole genome analyses acrossCochliobolusspecies identified 11 NRPS- and 21 PKS-encoding genes inC. miyabeanus. First purpose of the current study was to examine the effect of deletion of ten of the discontinuously distributed genes (corresponding to JGI protein IDs 4446, 5802, 6546, 7015, 9064, 41693, 41753, 83551, 98843 and 107726) on virulence ofC.miyabeanusto rice. A second purpose, based on results of the first, was to develop a PCR method to specifically identifyC. miyabeanusand to distinguish it from other closely related Cochliobolus spp. We show that deletion of seven of the genes resulted in mutants that were reduced in virulence compared to the wild-type strain WK1C. Wild-type developed large dark brown necrotic lesions surrounded by chlorotic halos, while the mutants produced smaller, light brown spots with chlorosis. These results suggest that the products of these genes contribute to brown spot disease. In addition, we identifiedPKSandNPSSNPs that discriminate betweenC. miyabeanusand other species ofCochliobolus.
Photoperiod decoder 1regulates seasonal changes in energy metabolism through the growth hormone signaling pathway
Authors: Nakayama Tomoya , Yamaguchi Taiki , Maruyama Michiyo , Ansai Satoshi , Kashima Makoto , Fontaine Romain , Henkel Christiaan , Naruse Kiyoshi , Yoshimura Takashi 
Published: February 2025

AbstractSeasonal changes in metabolism are crucial for animals to adapt to annual environmental fluctuations. However, the molecular mechanisms underlying these adaptations remain poorly understood. Here, we identified a novel gene,photoperiod decoder 1(phod1), which exhibits a unique bimodal expression pattern under long-day conditions in Japanese medaka fish (Oryzias latipes). Whilephod1is conserved across many vertebrates, except for eutherians, its function remained unknown. Single-cell RNA sequencing analysis revealed thatphod1is predominantly expressed in specific pituitary cells that co-express opsin and circadian clock genes. Transcriptomic analysis usingphod1knockout fish demonstrated thatphod1is essential for photoperiodic regulation of growth hormone. Furthermore, transcriptomic and metabolomic analyses of the liver, the primary target of growth hormone, revealed significant alterations in energy metabolism. Behavioral analysis also showed thatphod1knockout fish exhibited significantly reduced locomotor activity. These findings indicate thatphod1plays a crucial role in seasonal metabolic adaptation through modulation of the growth hormone signaling pathway.
Object representations drive emotion schemas across a large and diverse set of daily-life scenes
Authors: Gao Chuanji , Ajith Susan , Peelen Marius V. 
Published: February 2025

AbstractThe rapid emotional evaluation of objects and events is essential in daily life. While visual scenes reliably evoke emotions, it remains unclear whether emotion schemas evoked by daily-life scenes depend on object processing systems or are extracted independently. To explore this, we collected emotion ratings for 4913 daily-life scenes from 300 participants, and predicted these ratings from representations in deep neural networks and fMRI activity patterns in visual cortex. AlexNet, an object-based model, outperformed EmoNet, an emotion-based model, in predicting emotion ratings for everyday scenes, while EmoNet excelled for explicitly evocative stimuli. Emotion information was processed hierarchically within the object recognition system, consistent with the visual cortex’s organization. Activity patterns in the lateral occipital complex (LOC), an object-selective region, reliably predicted emotion ratings and outperformed other visual regions. These findings suggest that emotion processing in everyday scenes follows visual object recognition, with additional mechanisms engaged when object content is uninformative.