bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principled PCA separates signal from noise in omics count data
Authors: Stanley Jay S. , Yang Junchen , Li Ruiqi , Lindenbaum Ofir , Kobak Dmitry , Landa Boris , Kluger Yuval 
Published: February 2025

AbstractPrincipal component analysis (PCA) is indispensable for processing high-throughput omics datasets, as it can extract meaningful biological variability while minimizing the influence of noise. However, the suitability of PCA is contingent on appropriate normalization and transformation of count data, and accurate selection of the number of principal components; improper choices can result in the loss of biological information or corruption of the signal due to excessive noise. Typical approaches to these challenges rely on heuristics that lack theoretical foundations. In this work, we present Biwhitened PCA (BiPCA), a theoretically grounded framework for rank estimation and data denoising across a wide range of omics modalities. BiPCA overcomes a fundamental difficulty with handling count noise in omics data by adaptively rescaling the rows and columns – a rigorous procedure that standardizes the noise variances across both dimensions. Through simulations and analysis of over 100 datasets spanning seven omics modalities, we demonstrate that BiPCA reliably recovers the data rank and enhances the biological interpretability of count data. In particular, BiPCA enhances marker gene expression, preserves cell neighborhoods, and mitigates batch effects. Our results establish BiPCA as a robust and versatile framework for high-throughput count data analysis.
Defective pollen meiosis in Arabidopsis due to combined arabinan and galactan insufficiency
Authors: Kikuchi Takuma , Soga Kouichi , Kotake Toshihisa , Takahashi Daisuke 
Published: February 2025

AbstractThe development of pollen is critical or seed plants, and depends on precise cellular and molecular mechanisms. It is known that the cell wall plays a key role in the progression of pollen maturation. An earlier phase in pollen development is the meiosis of pollen mother cells (PMCs), the fundamental process for producing viable pollen grains. However, the significance of the cell wall during pre-meiosis processes has remained unclear. Pectin, a major component of the cell wall, is known to accumulate abundantly in pollen. To investigate the significance of the cell wall during pollen meiosis, we generated anarad1 gals2 gals3triple mutant ofArabidopsis thaliana, lacking the genes responsible for normal synthesis of arabinan and galactan, which constitute the side chains of pectin. Although vegetative growth and cell wall properties were comparable in wild-type (WT) andarad1 gals2 gals3, the pollen development in the mutant failed during meiosis. Immunohistochemical analysis showed that pectic arabinan and galactan accumulated in WT PMCs before meiosis, but this was not observed in mutant PMCs. We believe that this study is the first to demonstrate the critical role of cell wall components, specifically pectic arabinan and galactan, in the pre-meiosis processes of pollen development.HighlightPectic arabinan and galactan accumulate on the surface of pollen mother cells and this accumulation is essential for pollen meiosis.
Gibberellin-deactivating GA2OX enzymes act as a hub for auxin-gibberellin crosstalk inArabidopsis thalianaroot growth regulation
Authors: Kubalová Monika , Griffiths Jayne , Müller Karel , Jones Alexander M. , Fendrych Matyáš 
Published: February 2025

AbstractPlant bodies are built from immobile cells, making the regulation of cell expansion essential for growth, development, and adaptation. In roots, cell elongation executes the movement of the root tips through soil. This process is tightly controlled by numerous signaling pathways. Among these, gibberellin and auxin signaling stand out for their contrasting effects on root growth, interacting through complex crosstalk at multiple regulatory levels. Here we reveal the molecular basis of the auxin-gibberellin crosstalk in the model plantArabidopsis thaliana. We show that auxin signaling pathway steers the expression ofGIBBERELLIN 2-OXIDASES (GA2OX), key gibberellin-deactivating enzymes in the root elongation zone. GA2OX are negative regulators of root cell elongation;GA2OX8overexpression decreases gibberellin levels and inhibits root cell elongation, in contrast, thega2ox heptuplemutant roots show elevated gibberellin levels in the elongation zone and grow longer roots. Shoot derived auxin can regulateGA2OX8expression in roots, linking systemic auxin signaling to local gibberellin modulation. In addition,GA2OX8is active in vascular tissues and the stem cell niche, tissues with high auxin levels. Loss ofGA2OXgenes results in altered stem cell niche, including increased quiescent center size and expanded root cell layers, highlighting the role of these enzymes in maintaining tissue organization. Together, our findings identify GA2OX6 and GA2OX8 enzymes as key mediators of auxin-gibberellin crosstalk, providing insights into their roles in root elongation, vascular development, and stem cell niche maintenance. These results expand our understanding of how auxin integrates with gibberellin signaling to coordinate root development and growth dynamics.
Volatile-Mediated Plant Defense Networks: Field Evidence for Isoprene as a Short-Distance Immune Signal
Authors: Zhu Peiyuan , Weber Baris , Rosenkranz Maaria , Polle Andrea , Ghirardo Andrea , Muhr Jan , Vlot A. Corina , Schnitzler Jörg-Peter 
Published: February 2025

AbstractIsoprene, the most abundant hydrocarbon emitted by vegetation, protects photosynthesis against oxidative and thermal stress and significantly impacts atmospheric chemistry. While laboratory studies suggest a role for isoprene in plant defense, its function in plant-plant communication under natural conditions remains unclear. Here, we demonstrate that isoprene acts as a signaling molecule, triggering systemic immune responses in neighboring plants against bacterial pathogens under field conditions. We established an experimental system using wild-type and transgenic silver birch (Betula pendula) lines engineered to emit varying levels of isoprene. Over two growing seasons, we examined the effects of birch-emitted volatile organic compounds on neighboring Arabidopsis thaliana, including wild-type and immune signaling mutants (llp1: legume lectin-like protein 1;jar1: jasmonate resistant 1). Isoprene emission rates positively correlated with systemic resistance in receiver plants, with higher emissions enhancing inhibition ofPseudomonas syringaegrowth. This immune response occurred independently of jasmonate signaling but required functional LLP1, suggesting a specific recognition pathway. By combiningArabidopsismutant responses with birch volatile profiles, we confirmed that isoprene, rather than other terpenoids, mediates this effect. These findings reveal an unrecognized ecological function of isoprene as an airborne immune signal, establishing transgenic birch as a robust model for studying volatile-mediated plant defense networks in natural environments. Our results provide new insights into the molecular mechanisms underlying plant volatile perception and expand our understanding of chemical communication in terrestrial ecosystems.Significance StatementIsoprene, the most abundant volatile organic compound released by plants, protects against abiotic stress. Here, we demonstrate that isoprene also functions under ambient atmosphere as a short-distance immune signal, enhancing neighboring plants’ resistance to bacterial pathogens. This finding reveals a putative ecological role of isoprene in plant defense networks and suggests strategies for sustainable agriculture and forest management under environmental stress.
The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity
Authors: Bigot Jeanne , Legendre Rachel , Hamroune Juliette , Jacques Sébastien , Legars Mathieu , Guillot Loïc , Corvol Harriet , Hennequin Christophe , Guitard Juliette , Coppée Jean-Yves , Balloy Viviane , Chica Claudia 
Published: February 2025

AbstractBackgroundInnate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure toPseudomonas aeruginosaflagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression.ResultsBy conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific factors (TFs) whose binding may drive this process.ConclusionsIn summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns
LoRA-DR-suite: adapted embeddings predict intrinsic and soft disorder from protein sequences
Authors: Lombardi Gianluca , Seoane Beatriz , Carbone Alessandra 
Published: February 2025

AbstractIntrinsic disorder regions (IDR) and soft disorder regions (SDR) provide crucial information on a protein structure to underpin its functioning, interaction with other molecules and assembly path. Circular dichroism experiments are used to identify intrinsic disorder residues, while SDRs are characterized using B-factors, missing residues, or a combination of both in alternative X-ray crystal structures of the same molecule. These flexible regions in proteins are particularly significant in diverse biological processes and are often implicated in pathological conditions. Accurate computational prediction of these disordered regions is thus essential for advancing protein research and understanding their functional implications. To address this challenge, LoRA-DR-suite employs a simple adapter-based architecture that utilizes protein language models embeddings as protein sequence representations, enabling the precise prediction of IDRs and SDRs directly from primary sequence data. Alongside the fast LoRA-DR-suite implementation, we release SoftDis, a unique soft disorder database constructed for approximately 500,000 PDB chains. SoftDis is designed to facilitate new research, testing, and applications on soft disorder, advancing the study of protein dynamics and interactions.
A simple approach to multiplexed PCR amplicon sequencing of plumage-associated loci inVermivorawarblers
Authors: Toews David P. L. , Besch Catharine E. 
Published: February 2025

AbstractThe dynamics of hybridization between golden-winged (Vermivora chrysoptera) and blue-winged warblers (V. cyanoptera) has been of interest for over a century. Whole genome analysis found only a small number of genomic regions that differed between the species. We previously developed a restriction enzyme-based RFLP approach to genotype large numbers of individuals at each of these loci. Here we extend this approach to an amplicon sequencing method to genotype individuals at these six plumage-associated regions. We demonstrate the efficacy using preliminary data from 4 golden-winged and 4 blue-winged warblers as well as provide the data and scripts necessary to analyze these data for other interested in replicating this approach. Our hope is that these data are useful for other researchers interested in genotypingVermivorawarblers.Additional methodshttps://github.com/david-toews/vermivora_amplicon
Shear Stress Conditioning Promotes a Pro-Inflammatory Response in Porcine Endocardial Endothelial Cells
Authors: Ji Pengfei , Grande-Allen Kathryn Jane , Balaji Swathi , Birla Ravi K. , Keswani Sundeep G. 
Published: February 2025

ABSTRACTPURPOSEDiscrete subaortic stenosis (DSS) is a congenital heart disease characterized by a narrowing of the passage below the aortic valve in the left ventricular outflow tract (LVOT) [1]. While endocardial endothelial cells (EECs) are known to play a role in DSS, the response of these cells to shear stress is not known. In this study, we hypothesize that the response of EECs to shear stress in the LVOT is a mediator of DSS.METHODSTo test this hypothesis, we conditioned porcine EECs to controlled shear stress regimes using cone and plate bioreactors. Subsequently, we quantified the concentration of proinflammatory cytokine in the conditioned media using the Luminex assay. Bulk-RNA sequencing was used to quantify changes in the genotype of the shear stress conditioned EECs.RESULTSThe expression of CD31 was knocked down and subsequently, the changes in release of shear stress induced proinflammatory cytokines released by EECs quantified using the Luminex assay. The results of these studies show that the inflammatory cytokines were highly selected in the conditioning medium, and under bioreactor treatment the cell activated the PI3K-AKT and TNF-a signaling, which also triggered the other immune cell responses though Th1, Th2 and Th17 cell differentiation pathways. Furthermore, CD31 was identified as a mediator of the pro-inflammatory response of shear stress conditioned EECs.CONCLUSIONSThe studies provide a clear link between shear stress, and the subsequent proinflammatory response of EECs as a mediator of DSS.
Mitochondrial metabolism is rapidly re-activated in mature neutrophils to support stimulation-induced response
Authors: Lika Jorgo , Votava James A. , Datta Rupsa , Kralovec Aleksandr M. , Smith Frances M. , Huttenlocher Anna , Skala Melissa C. , Fan Jing 
Published: February 2025

AbstractNeutrophils are highly abundant innate immune cells that are constantly produced from myeloid progenitors in the bone marrow. Differentiated neutrophils can perform an arsenal of effector functions critical for host defense. This study aims to quantitatively understand neutrophil mitochondrial metabolism throughout differentiation and activation, and to elucidate the impact of mitochondrial metabolism on neutrophil functions. To study metabolic remodeling throughout neutrophil differentiation, murine ER-Hoxb8 myeloid progenitor-derived neutrophils and human induced pluripotent stem cell-derived neutrophils were assessed as models. To study the metabolic remodeling upon neutrophil activation, differentiated ER-Hoxb8 neutrophils and primary human neutrophils were activated with various stimuli, including ionomycin, MSU crystals, and PMA. Characterization of cellular metabolism by isotopic tracing, extracellular flux analysis, metabolomics, and fluorescence-lifetime imaging microscopy revealed dynamic changes in mitochondrial metabolism. As neutrophils mature, mitochondrial metabolism decreases drastically, energy production is fully offloaded from oxidative phosphorylation, and glucose oxidation through TCA cycle is substantially reduced. Nonetheless, mature neutrophils retain the capacity for mitochondrial metabolism. Upon stimulation with certain stimuli, TCA cycle is rapidly activated. Mitochondrial pyruvate carrier inhibitors reduce this re-activation of the TCA cycle and inhibit the release of neutrophil extracellular traps. Mitochondrial metabolism also impacts neutrophil redox status, migration, and apoptosis without significantly changing overall bioenergetics. Together, these results demonstrate that mitochondrial metabolism is dynamically remodeled and plays a significant role in neutrophil function and fate. Furthermore, these findings point to the therapeutic potential of mitochondrial pyruvate carrier inhibitors in a range of conditions where dysregulated neutrophil response drives inflammation and contributes to pathology.
Improved Spatial Transcriptomics Clustering with Nested Graph Neural Networks
Authors: Jain Atishay , Laidlaw David H. , Ma Ying , Singh Ritambhara 
Published: February 2025

AbstractWe introduce a novel approach, STING, for spatial transcriptomic clustering analysis. Unlike existing state-of-the-art techniques that use graph-based neural networks (GNNs) trained on graphs generated from the spatial proximity of tissue locations (or spots), STING incorporates spot-specific related genes. This feature allows STING to better distinguish between clusters and identify meaningful gene-gene relations for knowledge discovery. It is a nested GNN framework that simultaneously models gene-gene and spatial relations. Using the gene expression, we generate a spot-specific gene-gene co-expression graph. We implement an inner GNN for these graphs to generate embeddings for each location. Next, we utilize these embeddings as features in a sample-wide graph generated using spatial information. We implement an outer GNN for this graph to reconstruct the original gene expression data. Finally, STING is trained end-to-end to generate embeddings that capture gene-gene and spatial information, which we input to a clustering algorithm to produce the spatial clusters. Experiments for 26 samples across 7 datasets and 5 spatial sequencing technologies show that STING outperforms the existing state-of-the-art techniques with a 1.58% to 4.07% improvement in the clustering evaluation metric, thus confirming that integrating gene-gene relation information with the clustering task leads to more informative embeddings and better clusters. Furthermore, experiments on a human breast cancer dataset show that STING identifies relevant genes and gene-gene relations, enabling biological hypothesis generation.
Single-cell RNA-seq reveals altered plasma cell subsets and decreased cytotoxicity of NK cells in patients with Kawasaki disease
Authors: Zhou Yuanlin , Liu Yan , Liu Li , Shen Xiaojia , Wen Xiaobin , Lin Guixu , Tang Lin , Li Qian , Gan Jingqiu , Li Ruixu , Shang Jin , Li Lei 
Published: February 2025

AbstractAimThe pathogenesis and therapeutic strategies of Kawasaki disease (KD) are worth further exploring. Using single-cell RNA sequencing (scRNA-seq), our study aimed to explore the landscape of peripheral blood mononuclear cells (PBMCs) in patients with KD.MethodsWe analyzed the scRNA-seq data of three patients with KD and three healthy controls from the GSE168732 dataset. Additionally, we explored the immune profiles and immune cell subtypes of patients with KD.ResultsSignificantly increased B cells and decreased NK cells were observed in the KD group compared with that in the control group. Furthermore, six B cell subsets were identified in the PBMCs of patients with KD. Particularly, plasma cells (CD9+and S100A9+B cell clusters) distinctly increased in the KD group. CD9+B cell cluster was characterized by vascular endothelial growth factor (VEGF) signaling-associated marker genes and DEGs. Meanwhile the S100A9+B cell cluster was characterized by platelet aggregation marker genes. As for NK cells, CD16+CD56dimNK cells were enriched in the KD group. Cytotoxicity-related activating receptors (KLRD1,KLRC3) and cytotoxicity-associated genes (PRF1, NKG7, GZMA, GZMH, GNLY) were downregulated in the KD group.ConclusionCD9+and S100A9+plasma cells may contribute to CALs in KD by upregulating VEGF and activating platelet. In addition, decreased cytotoxicity of NK cells mediated by KLRD1/KLRC3 receptor may play a vital role in the development of KD. Our results suggested that plasma cells and NK cells could be promising targets for the treatment of KD.
Anti-Diabetic Effects ofNigella sativa and Cichorium intybusin Animal Experimental Model
Authors: Kashif Muhammad , Nasir Amar , Aziz Muhammad Khizer , ur Rehman Aziz , Vincent Tom , Gonzalez Jean-Paul , Waheed Usman 
Published: February 2025

ABSTRACTDiabetes mellitus is a chronic metabolic disease in humans associated with severe complications with a significant impact on the health, life expectancy, and lifestyle of patients.The present study has been designed to examine the anti-hyperglycemic efficacy of two medicinal plants -Nigella sativaseeds andCichorium intybusleaves - and their combined effects on body weight and hematological/serological parameters in alloxan-induced diabetic rabbits.For this purpose, 30 adult rabbits were divided into six equal groups of five rabbits each. Group I was kept as the negative control, while all other groups received a single intravenous injection of alloxan monohydrate to induce diabetes: Group II as positive control; Group III received metformin hydrochloride; Group IV was fed powderedC. intybusplant leaves; Group V was givenN. sativaaqueous seeds extract; and Group VI was fed a combination ofC. intybusandN. sativa. Fasting blood glucose levels and body weight of rabbits were observed at 0 days (before treatment) to Day 28 and regularly monitored during the four-week experimental trial. Biochemical analysis, serum insulin level, and hematological parameters were measured at the end of the experiment.Results showed thatC. intybus, N. sativa, and their mixture significantly (p< 0.05) decreased the blood glucose levels, urea and creatinine levels, and enzyme levels in the blood. At the same time, body weight gain, red blood cell (RBC) count, white blood cell (WBC) count, and packed cell volume (PCV) % were increased in diabetic rabbits as compared with positive control rabbits. It was concluded that these plants have potential hypoglycemic effects and reduced diabetic complications in alloxan-induced diabetic rabbits. Further studies are needed to understand their potential for antidiabetic remedy.
Immune-induced TCR-like antibodies regulate specific T cell response
Authors: Kishida Kazuki , Kawakami Keisuke , Tanabe Hiroaki , Nakai Wataru , Yonekura Koji , Yokoyama Shigeyuki , Arase Hisashi 
Published: February 2025

AbstractAntigen-specific regulation of T cell response is crucial for limiting hyperimmune response. In this study, we discovered that antibodies specific to the antigen peptide-MHC class II complex are produced during helper T cell responses to various antigens. These antibodies specifically inhibited T cell receptor (TCR) recognition of MHC class II molecules presenting specific antigen peptide. We have termed these antibodies ‘immuneinduced TCR-like antibodies’ (iTabs). Immunization with peptides containing flanking residues induced iTabs, whereas immunization with peptides lacking flanking residues did not. Furthermore, immunization of iTab-inducible peptide as well as iTab treatment suppressed autoimmune disease development. Our findings provide a strategy for suppressing antigen-specific helper T cell responses using specific peptides, potentially controlling autoimmune diseases.