bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineation of Single-cell Altas Provides New Insights for Development of Coronary Artery Lesions in Kawasaki Disease: Bad and Good Signaling Molecules
Authors: Lin Qiuping , Lv Xin , Qiu Qingzhu , Mei Lianni , Chen Liqin , Song Sirui , Liu Wei , Jiang Xunwei , Huang Min , Shen Libing , Xiao Tingting , Xie Lijian 
Published: November 2024

AbstractBackgroundKawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever and mainly affects children under 5 years of age. It is the leading cause of acquired heart disease in the form of coronary artery lesions (CALs) for children in developed countries. Most KD can be relieved with the high-dosage Intravenous immunoglobulin (IVIG) therapy, but a small proportion develop CALs after IVIG treatment.MethodsWe performed the single-cell RNA sequencing for the peripheral blood mononuclear cells (PBMCs) from three KD non-CAL patients whose samples were acquired before and after IVIG treatment and three KD CAL patients whose samples were acquired only after IVIG treatment. Cell-to-cell communication patterns were also analyzed in KD CAL and non-CAL patientsResultsOverall cell expression feature analyses show immunoglobulin and adaptive immunity related genes are upregulated in KD CAL patients while B cell activation related genes are downregulated in them. Pseudo-time analyses demonstrate that both KD non-CAL patients before treatment and KD CAL patients after treatment have a dysregulated B cell developmental trajectory while the former has a mixed T and B lineage and the latter has a mixed monocyte and B lineage. The early elevated expression of SPI1 could partly explain the dysregulated B cell development in KD CAL patients. Cell communication analyses propose a disorder cell communication pattern in KD non-CAL patients before treatment and some persistent bad cell-to-cell signals in KD CAL patients after treatment. There are four signaling molecules, APP, CCL, and MCH-II, whose expression is significantly increased in the CD14 and CD16 monocytes of KD CAL patients, where the expression of RESISTIN is significantly increased in those KD non-CAL patients.ConclusionsOur results suggest that APP, CCL, and MCH-II might be the bad signals for indicating the possible development of CAL while RESISTIN is a good one for protecting from CAL.
Acute Myeloid Leukemia with deletion 5q is an epigenetically distinct subgroup defined by heterozygous loss ofKDM3B
Authors: Kelly Katherine , Welte Linda , Sollier Etienne , Riedel Anna , Brown-Burke Fiona , Scherer Michael , Keer Harold N. , Azab Mohammad , Jahn Ekaterina , Döhner Hartmut , Döhner Konstanze , Lutsik Pavlo , Plass Christoph 
Published: November 2024

AbstractAcute myeloid leukemia (AML) is a hematological malignancy characterized by a block in differentiation and accelerated proliferation of myeloid progenitor cells. Genes encoding for epigenetic regulators are among the most frequent targets for mutations and structural variations in AML, giving rise to profound epigenetic heterogeneity between and within tumors. Deletions of chromosome 5q [del(5q)] are among the most common copy number alterations in AML and are associated with extremely poor clinical outcome and therapy resistance, however the mechanisms linking del(5q) to leukemic progression are not understood. Analyzing DNA methylation profiles from 477 elderly AML patients using DNA methylome deconvolution, we discovered that del(5q) AML is an epigenetically distinct subgroup characterized by a signature of DNA hypermethylation, which we propose may be linked to dysregulation of H3K9me1/2 and overexpression of the leukemic stem cell marker,DNMT3B. Interrogation of the minimally deleted 5q region highlighted the H3K9me1/2 demethylase KDM3B as a likely target for haploinsufficiency in this subgroup. Our data suggest that del(5q) AML should be reconsidered as an epigenetically dysregulated subgroup, driven by heterozygous loss ofKDM3B, and that the resulting imbalance of H3K9me1/2 may contribute to the progression of these aggressive leukemias.
A Robust Computational Framework for the Optimization of CDK7 Inhibitors as Promising Cancer Therapy
Authors: Shi Zhaoqi , Gao Xufan , Buratto Damiano , Zhou Ruhong 
Published: November 2024

AbstractCyclin-dependent kinase 7 (CDK7) plays a crucial role in cell cycle regulation and transcription, establishing it as a promising target for cancer therapy. Although the covalent inhibitor THZ1 effectively targets CDK7, it presents risks such as short half-life and potential off-target side effects. To address these limitations, we employed a computational workflow integrating virtual screening, molecular dynamics (MD) simulations, and free energy perturbation (FEP) method to design non-covalent CDK7 inhibitors with enhanced selectivity and safety profiles. MD simulations elucidated THZ1’s inhibitory mechanism and identified key molecular fragments within its structure. By incorporating fragments from known inhibitors, we introduced extensive non-covalent interactions within the binding pocket, leading to the identification of three novel non-covalent inhibitors with binding affinities comparable to or higher than that of THZ1. Our findings not only introduce promising CDK7 inhibitors but also present a robust computational framework that could accelerate the discovery of kinase-targeted therapeutics.
A Multi-Property Optimizing Generative Adversarial Network for de novo Antimicrobial Peptide Design
Authors: Liu Jiaming , Cui Tao , Wang Tao , Zeng Xi , Niu Yinbo , Jiao Shaoqing , Lu Dazhi , Wang Jun , Xiao Shuyuan , Xie Dongna , Wang Xuecheng , Wang Yongtian , Shang Xuequn , Wei Zhongyu , Peng Jiajie 
Published: November 2024

AbstractAntimicrobial peptides (AMPs) play a crucial role in developing novel antiinfective drugs due to their broad-spectrum antimicrobial activity and lower likelihood of causing bacterial resistance. However, laboratory synthesis of AMPs is tedious and time-consuming. Existing computational methods have limited capability in optimizing multiple desired properties simultaneously. Here, we propose a Multi-Property Optimizing Generative Adversarial Network (MPOGAN), a feedback-loop framework that iteratively learns from data with multiple desired properties. This approach enables de novo design of AMPs with potent antimicrobial activity, reduced cytotoxicity, and diversity. Through extensive computational tests, MPOGAN exhibits superior performance in optimizing multiple desired properties of generated AMPs. Ten of the most promising candidates are chemically synthesized, with nine showing potent antimicrobial activity against three bacterial strains and low cytotoxicity against eukaryotic cells. MPOGAN offers a powerful computational approach for effective multi-property optimization of AMPs, thereby advancing the field of AI-aided drug discovery.
Shading does not lower thermal tolerance in the coralMontipora capitata: implications for conservation intervention
Authors: Ducret Hugo , Suchocki Christopher R. , Bardin Claire E. , Lewis Claire J. , Permentier Tristan , Hardt Madeleine , Toonen Robert J. , Kochzius Marc , Flot Jean-François 
Published: November 2024

AbstractMarine heatwaves trigger severe coral bleaching events that result in dramatic losses of coral reefs worldwide. An increasingly common method used to mitigate coral bleaching is to shade portions of reefs. However, as shaded corals become less exposed to environmental stress, shading has also been hypothesized to lower their thermal tolerance, which would be detrimental for their survival. Here, we investigated how long-term shading modifies the response ofMontipora capitatato both light and temperature stressors. After two years of growth, we used the Coral Bleaching Automated Stress System (CBASS) to compare responses of 73% shaded and unshaded corals during 1) temperature stress under ambient light, 2) temperature stress under low light, and 3) ambient temperature with light stress. Results show that shaded corals are less resistant than control ones to light stress and to heat stress under high light, but not to heat stress under low light, where no difference was detected. We further demonstrate that low light intensity during heat stress reduces the decline of photosynthetic efficiency when compared to heat stress at ambient light, regardless of the light history of the coral colonies. Our data support light-mediated stress, both independent of and synergistic with heat-induced stress, and suggest that light and heat stresses trigger different molecular and cellular pathways. We hereby confirm the benefits of coral shading under both short– and long-term temperature stress, and underline the importance of light acclimation in the conservation and restoration of coral reefs.
T cell receptor sharing in hypersensitivity pneumonitis
Authors: Sendama Wezi , Funston Wendy , Davidson Richard CH , Rostron Anthony J , Simpson A John 
Published: November 2024

AbstractHypersensitivity pneumonitis (HP) is characterised by an excessive pulmonary T cell response in susceptible individuals after exposure to inhaled antigens. The most effective treatment for the condition is antigen avoidance, but in most cases an antigen cannot be identified. Profiling antigen-specific T cell responses may form the basis of a strategy to identify causative antigens of the disease. We used public RNA sequencing data and reconstructed T cell receptor (TCR) repertoires from blood and bronchoalveolar lavage samples from patients with HP, idiopathic pulmonary fibrosis and healthy controls. After excluding TCR sequences likely to be related to common microbial exposures in patients with HP, we identified TCRs shared between patients with shared human leukocyte antigen alleles, indicating patients likely to have a common causative antigen. We also identified clusters of TCRs containing identical and similar TCR clones in individual patients that are plausibly related to the causative antigens in those patients. These results establish the feasibility of profiling TCR repertoires to identify antigens in HP.
DDA-BERT: leveraging transformer architecture pre-training for data-dependent acquisition mass spectrometry-based proteomics
Authors: Jun A , Liu Pu , Sun Yingying , Lin Jiaying , Zhang Xiaofan , Nie Zongxiang , Zhang Yuqi , Xing Ziyuan , Chen Yi , Guo Tiannan 
Published: November 2024

AbstractIn data-dependent acquisition mass spectrometry (DDA-MS)-based proteomics, machine learning based rescoring methods are often employed to integrate multiple scores measuring quality of peptide-spectrum matches (PSMs) from different aspects. Existing rescoring tools face limitations incurred by manual feature extraction, shallow machine learning models, and limited training data. Here, we introduce DDA-BERT, a transformer-based end-to-end deep learning model trained with 95 million human spectra for PSM rescoring. DDA-BERT demonstrates superior performance across various sample types, mass spectrometer platforms, trace sample proteomics, and multiple species proteome data. It consistently outperforms state-of-the-art methods of its kind for DDA-MS spectra analysis with up to 103.5% increased protein group identifications. For single cell proteomics, DDA-BERT identifies up to 85.6% more protein groups compared to existing tools. In addition, DDA-BERT can be effectively extended to proteome of non-human species. DDA-BERT offers a robust and scalable solution for enhancing PSM rescoring in proteomics.
Building a single cell transcriptome-based coordinate system for cell ID with SURE
Authors: Zeng Feng , Han Jiahuai 
Published: November 2024

SummaryThe surge in single-cell transcriptome data necessitates a unified cell identification system. We propose a strategy that uses metacells as landmarks, coupled with a data-driven method called SURE, to create a cell ID coordinate system. This system streamlines cell atlases, enhances molecular signals, and ensures accurate cell identification while mitigating sequencing noise. We demonstrated the effectiveness of SURE by assembling similar cell types from datasets with cell type imbalance issues. We employed SURE to establish a unified coordinate system for the human hematopoietic system (HBMCA), which enables the direct, zero-shot mapping of single-cell datasets from 13 different diseases, showcasing its value as a common foundation for investigating the diverse disease effects on human blood cells. SURE has successfully addressed the long-standing challenge of positioning cells within a common multidimensional space, paving the way for a convergent understanding of cell identity across diverse experimental landscapes.
The firstde novoHiFi genome assemblies for three clownfish-hosting sea anemone species (Anthozoa: Actiniaria)
Authors: De Jode Aurélien , Titus Benjamin M. 
Published: November 2024

AbstractThe symbiosis between clownfish and giant tropical sea anemones (Order Actiniaria) is one of the most iconic on the planet. Distributed on tropical reefs, 28 species of clownfishes form obligate mutualistic relationships with 10 nominal species of venomous sea anemones. Our understanding of the symbiosis is limited by the fact that most research has been focused on the clownfishes. Chromosome scale reference genomes are available for all clownfish species, yet there are no published reference genomes for the host sea anemones. Recent studies have shown that the clownfish-hosting sea anemones belong to three distinct clades of sea anemones that have evolved symbiosis with clownfishes independently. Here we present the first high quality long read assemblies for three species of clownfish hosting sea anemones belonging to each of these clades:Entacmaea quadricolor, Stichodactyla haddoni, Radianthus doreensis. PacBio HiFi sequencing yielded 1,597,562, 3,101,773, and 1,918,148 million reads forE. quadricolor, S. haddoni, andR. doreensis, respectively. All three assemblies were highly contiguous and complete with N50 values above 4Mb and BUSCO completeness above 95% on the Metazoa dataset. Genome structural annotation with BRAKER3 predicted 20,454, 18,948 and 17,056 protein coding genes inE. quadricolor, S. haddoniandR. doreeensisgenome, respectively. These new resources will form the basis of comparative genomic analyses that will allow us to deepen our understanding of this mutualism from the host perspective.SignificanceChromosome-scale genomes are available for all 28 clownfish species yet there are no high-quality reference genomes published for the clownfish-hosting sea anemones. The lack of genomic resources impedes our ability to understand evolution of this iconic symbiosis from the host perspective. The clownfish-hosting sea anemones belong to three clades of sea anemones that have evolved mutualism with clownfish independently. Here we assembled the first high-quality long-read genomes for three species of host sea anemones each belonging to a different host clade:Entacmaea quadricolor, Stichodactyla haddoni, Radianthus doreensis. These resources will enable in depth comparative genomics of clownfish-hosting sea anemones providing a critical perspective for understanding how the symbiosis has evolved. Finally, these reference genomes present a significant increase in the number of high-quality long-read genome assemblies for sea anemones (11 currently published) and double the number of high-quality reference genomes for the sea anemone superfamily Actinoidea.
Companion to: A molecular basis for milk allergen immune recognition in eosinophilic esophagitis
Authors: Dilollo Julianna , Hu Alex , Qu Huiqi , Canziani Karina E. , Clement Rachel L. , McCright Sam J. , Shreffler Wayne G. , Hakonarson Hakon , Spergel Jonathan M. , Cerosaletti Karen , Hill David A. 
Published: November 2024

ABSTRACTBackgroundEosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease that is increasing in incidence and has substantial morbidity. Despite being clinically defined as a food allergy, the molecular details of food antigen presentation and recognition by the immune system are unknown.ObjectiveThe objective of this study was to identify and characterize the molecular basis of milk antigen presentation and T cell recognition in a patient with EoE milk allergy.MethodsMilk-expanded TCR clonotypes were identified usingex vivostimulation followed by single cell RNA with linked, pairedTRAandTRBsequencing. HLA restriction and antigen specificity of TCRs were identified using a combination of lentiviral expression, HLA sequencing, antibody blockade, and a peptide library screen.ResultsWe isolated a β-casein specific TCR clonotype (eoeTCR-4) and determined its HLA restriction (HLA-DRB1*07:01) and cognate antigen (β-casein AA 59-78). EoeTCR-4 was not detected among a larger group of subjects and is likely private to EoE Subject 1.ConclusionIn conjunction with the parent manuscript, this companion article provides the first molecular identity of food antigen presentation and immune recognition in EoE.SUMMARYThis manuscript is a companion to the parent manuscript “A molecular basis for milk allergen immune recognition in eosinophilic esophagitis”. It provides additional data and detailed methods not provided in the parent manuscript. It is designed to supplement and support the findings and conclusions of the parent manuscript.
Lipid Nanoparticles fromL. meyeniiWalp Mitigate Sepsis through Multimodal Protein Corona Formation
Authors: Sung Junsik J. , Shaw Jacob R. , Rezende Josie D. , Dharmaraj Shruti , Cottingham Andrea L. , Weldemariam Mehari M. , Jones Jace W. , Kane Maureen A. , Pearson Ryan M. 
Published: November 2024

AbstractBackgroundPlant-derived nanoparticles (PDNP) are nano-sized particles isolated from various edible plants that contain bioactive components involved in regulating cellular immune responses against pathogenic intrusion and inflammation.PurposeThis study describes a novel PDNP derived fromLepidium meyeniiWalp (maca) that efficiently captures pro-inflammatory cytokines and acute phase proteins in its protein corona to enhance survival in two representative lethal models of sepsis.MethodsLipid nanoparticles were isolated from maca (MDNP) and triacylglycerols and phytoceramides were identified as major constituents using lipidomics. The physicochemical properties of MDNPs were determined, anti-inflammatory effects of MDNP were evaluated usingin vitromodels andin vivousing endotoxemia and cecal ligation and puncture (CLP) polymicrobial sepsis models. Proteomic analysis of MDNP in healthy or LPS-induced inflammatory plasma was used to determine the composition and inflammatory pathways modulated due to the MDNP protein corona.ResultsIn vitrostudies showed that MDNP were non-toxic, reduced macrophage activation, and effectively sequestered pro-inflammatory cytokines to mitigate NF-κB activity under lipopolysaccharide (LPS) stimulation. In a pre-established LPS-induced endotoxemia model, MDNP-treated mice showed significantly reduced systemic pro-inflammatory cytokines and enhanced survival. Untargeted proteomics and pathway analysis of the MDNP protein corona identified an enrichment in acute phase proteins in MDNP-LPS plasma coronas. MDNP treatment also significantly improved survival in the CLP sepsis model in the absence of antibiotics.ConclusionThis work identified MDNP as an efficient, plant-derived lipid NP that broadly sequesters and neutralizes a compilation of inflammatory mediators in their coronas, offering multimodal therapeutic potential for treating inflammatory diseases.
Physiologic Regulation of Lipid Oxidation and Ferroptosis By Vitamin E, High-Density Lipoprotein, and Scavenger Receptor Class B Type 1
Authors: Rink Jonathan S. , Calvert Andrea E. , Moxley Alexandra , Lin Adam Yuh , Nguyen SonBinh T. , Gordon Leo I , Thaxton C. Shad 
Published: November 2024

ABSTRACTFerroptosis is a form of cell death caused by oxidative (-OOH) damage to phospholipids (PL) that comprise the cell membrane. Understanding mechanisms of ferroptosis is important because of the role it plays in human disease, including cancer and neurodegeneration. Previous work has focused on the intracellular antioxidant enzyme glutathione peroxidase 4 (GPx4), which detoxifies PL-peroxides (PL-OOH) and prevents ferroptosis. Studies also show that alpha-tocopherol (α-toc), the active form of Vitamin E, is an exogenous lipophilic antioxidant that inhibits ferroptosis in cancer cells in vitro and in neurons and hematopoietic stem cells in vivo. The mechanisms by which α-toc engages cells to manipulate PL redox balance and ferroptosis are unknown. Lipoproteins, like high- and low-density lipoproteins (HDL and LDL), carry α-toc in the circulation, which compelled our investigation of their role in α-toc delivery and ferroptosis. Using cancer and neuronal cell models, here we show that lipoproteins, particularly HDL, deliver α-toc by binding the cell membrane receptor scavenger receptor class B type 1 (SR-B1) to prevent ferroptosis. Additionally, we synthesized SR-B1 targeted HDL-like particles that contained α-toc to validate data obtained with native lipoproteins. We reveal here a tunable cellular redox axis whereby native and synthetic HDLs containing α-toc target SR-B1 to reduce PL-OOH and prevent ferroptosis.
Evolution of pineal non-visual opsins in lizards and the tuatara (Lepidosauria)
Authors: Romero Ricardo , de Souza Flávio S J 
Published: November 2024

AbstractMany lizards (Squamata), as well as the tuatara (Rhynchocephalia), are distinguished among vertebrate groups for the presence of the parietal eye - also called “third eye” - a structure derived from the pineal complex that develops from the roof of the diencephalon and resembles a simplified retina. The parietal eye is located near the dorsal surface of the head and possesses photoreceptor cells expressing an array of nonvisual opsins that differs from the visual opsin repertoire of the lateral eyes. These pineal opsins are pinopsin (OPNP), parapinopsin (OPNPP) and parietopsin (OPNPT), all being evolutionary close to the visual opsins. A fourth member of the group, vertebrate-ancient opsin (OPNVA), is expressed in the brain. Here, we have searched over 50 lepidosaurian genomes (tuatara + lizards) for pineal non-visual opsins to check for the evolutionary trajectory of these genes during reptile evolution. Unexpectedly, we identified a novel opsin gene, which we termed “lepidopsin” (OPNLEP), that is present in the tuatara and most lizards but absent from the genomes of other reptiles. Phylogenetic analyses indicate that OPNLEP proteins are grouped in a clade distinct from nonvisual and visual opsins. Remnants of the gene are found in the coelacanth and some ray-finned fishes like gars and sturgeons, implying that OPNLEP is an ancient opsin that has been repeatedly lost during vertebrate evolution. As for the survey, we found that the tuatara and most lizards of the Iguania, Anguimorpha, Scincoidea and Lacertidae clades, which possess a parietal eye, harbour all five non-visual opsin genes analysed. Lizards missing the parietal eye, like geckos (Gekkota), the fossorialRhineura floridana(Amphisbaenia) and lacertoids of the Teiidae and Gymnophthalmidae families lack most or all pineal nonvisual opsins. In summary, our survey of reptile pineal non-visual opsins has revealed i) the persistence of a previously unknown ancient opsin gene – OPNLEP - in lepidosaurians; ii) losses of non-visual opsins in specific lizard clades and iii) a correlation between the presence of a parietal eye and the genomic repertoire of pineal non-visual opsins.