bluuebunny/crossref_metadata_2025_split huggingface dataset:
NR6A1 is essential for neural crest cell specification, formation and survival
Authors: Moore Zajic Emma L. , Muñoz William A. , Dennis Jennifer F , Bhatt Shachi , Sakai Daisuke , Achilleos Annita , Zhao Ruonan , Lamb Maureen , Price Andrew J , Seidel Chris , Tiana María , Barral Antonio , Clawson Delaney , Manzanares Miguel , Trainor Paul A. 
Published: January 2025

AbstractNeural crest cells (NCC) are a migratory progenitor cell population considered unique to vertebrates. Derived from the neuroepithelium during early embryogenesis, NCC contribute to nearly every tissue and organ system throughout the body, and disruptions in NCC development can result in congenital disorders, termed neurocristopathies. Despite decades of research, we have a poor understanding of the cellular mechanisms and signals that govern mammalian NCC formation. We discovered nuclear receptor superfamily 6 group member 1 (NR6A1/GCNF/RTR), is a novel, critical regulator of mammalian NCC specification, formation and survival.Nr6a1is expressed throughout the neuroepithelium in mouse embryos from E8.0 to E9.5 and briefly in newly delaminated NCC. Nr6a1 loss-of-function perturbs anterior cranial NCC formation and survival, and results in the complete agenesis of migratory NCC caudal to the first pharyngeal arch. Using mouse ESC and human iPSC differentiation into NCC, chromatin immunoprecipitation, and multiomic approaches, we demonstrate that these phenotypes are associated with perturbation of NCC specification (Foxd3, Sox9, Sox10) and epithelial-mesenchymal transition (EMT;Snail1, Zeb2), in concert with persistent expression of pluripotency-associated factors (Oct4andNanog) in the neuroepithelium. Conditional deletion revealed that Nr6a1 is required during mid-late gastrulation, demonstrating that murine NCC specification occurs earlier than previously thought. Consistent with these observations,in vivooverexpression ofOct4in gastrulating mouse embryos disrupts NCC specification and formation. Therefore, Nr6a1 is essential for mammalian NCC formation and moreover, may function as a bimodal switch repressing pluripotency-associated factors in the neuroepithelium, while concomitantly activating NCC specifiers and regulators of EMT.
Sustained Isobutene Production bySynechocystissp. PCC 6803 Entrapped in Polyvinyl Alcohol Hydrogel Beads
Authors: Vajravel Sindhujaa , Aravind Sanjukta , Stensjö Karin 
Published: January 2025

AbstractCyanobacteria convert CO2into valuable compounds using solar energy, making them ideal for sustainable isobutene production, a key precursor for fuels and chemicals. This study aimed to enhance isobutene production in engineeredSynechocystissp. PCC 6803 strains: Syn-RnKICD, producing isobutene from α-ketoisocaproate (KIC) viaRattus norvegicusα- ketoisocaproate dioxygenase (RnKICD), and Syn-F336V, expressing a mutant variant ofRnKICD with improved KIC specificity. We investigated the effects of varying culture conditions, including light intensity, inorganic carbon, and nitrogen on isobutene production. Nitrogen limitation emerged as a critical factor, improving yields by reducing growth. This likely occurred due to decreased competition from branched-chain amino acid (BCAA) biosynthesis, redirecting carbon toward isobutene synthesis. However, prolonged nitrogen limitation ultimately reduced productivity due to impaired metabolic functions. To address this limitation, we employed a polyvinyl alcohol-sodium alginate (PVA-SA) hydrogel, crosslinked with B(OH)₄⁻ and Ca²⁺, to entrap cells. This approach restricted growth while maintaining cell viability and isobutene productivity. Optimizing crosslinking parameters such as time, pH, and the hydrogel-to-cell mass ratio improved bead stability under bicarbonate and nitrate supply. This strategy extended cell viability and isobutene productivity in Syn-RnKICD and Syn- F336V by nearly a month, increasing yields by 60% and 80%, respectively, compared to suspension cells, achieving a maximum yield of 94 mg/g DW. This study underscores the importance of optimizing environmental conditions for isobutene production inSynechocystisand highlights the effectiveness of PVA-SA cell entrapment as a biocatalyst platform for sustained chemical production.HighlightsOptimized light, carbon, and nitrogen sources enhanced isobutene production.Rate of isobutene production increased 10-fold compared to our previous report.Nitrogen limitation improved isobutene yield by redirecting carbon from growth.PVA-entrapped cells sustained isobutene productivity for nearly 31 days.
High-resolution digital dissociation of brain tumors with deep multimodal autoencoder
Authors: Sun Jiao , Pan Yue , Lin Tong , Smith Kyle , Onar-Thomas Arzu , Robinson Giles W. , Zhang Wei , Northcott Paul A. , Li Qian 
Published: January 2025

AbstractSingle-cell technologies enable high-resolution, multi-dimensional analysis of molecular profiles in cancer biology but face challenges related to low coverage and cell annotation. The inherent hetero-geneity and complexity of brain tumors may hinder large-scale single cell multi-omic profiling. An efficient alternative is digital dissociation, which involves quantifying cell abundance and purifying bulk samples at high resolution. However, most existing tools for resolving bulk transcriptomes using scRNA-seq as a reference are not easily transferred to other omics (e.g., chromatin accessibility, DNA methylation, protein) due to ambiguous cell markers. Here, we introduce MODE, a novel multimodal autoencoder neural network designed to jointly recover personalized multi-omic profiles and estimate multimodal cellular compositions. MODE is the first algorithm trained on large-scale pseudo-bulk multi-omics derived from an external scRNA-seq reference and an individualized non-RNA reference panel constructed from target tumors. The accuracy of MODE was evaluated through an extensive simulation study, which generated realistic multi-omic data from distinct tissue types. MODE outperformed existing deconvolution pipelines with superior generalizability. Additionally, the high-resolution multi-omic profiles purified by MODE showed strong fidelity and enhanced power to detect differentially expressed genes. We applied MODE to bulk methylome-transcriptome data from two independent brain tumor cohorts, revealing modality-specific cellular landscapes in pediatric medul-loblastoma (MB) and adult glioblastoma (GBM). In MB tumors, MODE accurately predicted the composition of embryonal lineage cells and their marker genes expression. In GBM, the deconvoluted cellular composition revealed an increased myeloid cell abundance associated with poorer event-free survival. Overall, MODE high-resolution multimodal dissociation unravels the origins, evolution, and prognosis of pediatric and adult brain tumors, offering a powerful tool for multi-omic analysis at cell state resolution without large-scale single cell sequencing. MODE is a pipeline freely available athttps://github.com/jsuncompubio/MODE.
A single-cell transcriptome atlas of adult male and female human hookwormAncylostoma ceylanicum
Authors: Bharti Suman , Rosa Bruce A , Martin John , Mitreva Makedonka 
Published: January 2025

SummaryHookworms infect over 500 million people globally and represent a major neglected tropical disease. The prevalence, high reinfection rate, limited drugs and emerging resistance underscore the need for new therapeutic or vaccine targets. To mitigate halted progress of discovering targets, we provide new molecular insights into sex-specific expression and cellular heterogeneity by generating the first single-cell atlas of male and female transcriptome for the human hookwormAncylostoma ceylanicum. We systemically annotated 10 transcriptionally distinct cell types in female and 13 in male hookworm by comparing marker genes with tissue-specific knowledge. Non-reproductive tissues included pharynx, intestine, cephalic and pharyngeal glands, muscle and hypodermis, complemented with female reproductive tissues (ovary, uterus, eggs, seminal receptacle), and male reproductive tissues (testis, seminal vesicle, cement gland, sperm). Anatomical confocal microscopy and fluorescence in situ hybridization assisted in visualizing these tissues and confirming marker genes. Functional comparisons revealed previously undescribed tissue pathways and molecular markers, providing previously unrecognized insights into hookworm biology, and new targets. Overall, this study presents a detailed cell-type atlas for adult stages of this important yet neglected metazoan parasite.Graphical abstract
Facilitation of CaV3.2 channel gating in pain pathways reveals a novel mechanism of serum-induced hyperalgesia
Authors: Sanner Karolina , Kawell Sarah , Evans J. Grayson , Elekovic Vida , Walz MacKenzie , Joksimovic Sonja Lj. , Joksimovic Srdjan M. , Donald Rebecca R. , Tomic Maja , Orestes Peihan , Feseha Simon , Dedek Annemarie , Ghodsi Seyed Mohammadreza , Fallon Isabella P. , Lee Jeonghan , Hwang Sung Mi , Hong Sung Jun , Mayer John P. , Covey Douglas F. , Romano Carmelo , Timic Stamenic Tamara , Chemin Jean , Bourinet Emmanuel , Poulen Gaetan , Longon Nicolas , Vachiery-Lahaye Florence , Bauchet Lue , Zorumski Charles F. , Stowell Michael H. B. , Hildebrand Michael E. , Eisenmesser Elan Z. , Jevtovic-Todorovic Vesna , Todorovic Slobodan M. 
Published: January 2025

AbstractThe CaV3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability of nociceptive neurons; the endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover a novel peptide albumin (1-26) that facilitates channel gating by chelating trace metals that tonically inhibit CaV3.2viaH191 residue. Importantly, serum also potently modulated T-currents in human and rodent dorsal root ganglion (DRG) neurons.In vivopain studies revealed that injections of serum and albumin (1-26) peptide resulted in robust mechanical and heat hypersensitivity. This hypersensitivity was abolished with a T-channel inhibitor, in CaV3.2 null mice and in CaV3.2 H191Q knock-in mice. The discovery of endogenous chelators of trace metals in the serum deepens our understanding of the role of CaV3.2 channels in neuronal hyperexcitability and may facilitate the design of novel analgesics with unique mechanisms of action.
The WRC domain of GRF transcription factors. Structure and DNA recognition
Authors: Biglione Franco A. , Palatnik Javier F. , González Schain Nahuel D. , Rasia Rodolfo M. 
Published: January 2025

AbstractGrowth-regulating factors (GRFs) belong to a plant-specific family of transcription factors which display important roles in plant growth and development. GRF transcriptional activity is finely tuned by regulatory processes involving post-transcriptional silencing exerted by miRNA396, and protein-protein interactions involving a family of co-transcriptional regulators known as GRF-interacting factors (GIFs). In this way, expression of GRF target genes is modulated by a highly complex interplay between GRF/GIF isoform diversity and expression patterns along with miR396 and GIF gradients throughout plant tissues. At the protein level, GRFs are composed of two highly conserved domains known as QLQ and WRC and a less conserved C-terminal trans-activation domain. Whereas QLQ mediates GRF-GIF interaction by forming a complex with SNH domains found in GIFs, the WRC has been proposed as a putative zinc finger domain responsible for target DNA recognition and nuclear import. However, the structural aspects governing GRF transcriptional activity and target recognition remain unknown. In this work, we applied bioinformatic and biophysical analysis to comprehensively characterize the structural features that modulate the biological function of this protein family with a focus on the WRC domain. We provide insights into the structure of the WRC domain in GRFs and explore the WRC features driving GRFs:DNA complex formation. These findings offer new insights into how WRC domains modulate the biological functions of GRFs, laying the groundwork for future studies on their structure-function relationship in gene regulation and development of plants.
Dynamic remodeling of centrioles and the microtubule cytoskeleton in the lifecycle of chytrid fungi
Authors: Long Alexandra F. , Vasudevan Krishnakumar , Swafford Andrew J.M. , Venard Claire M. , Stajich Jason E. , Fritz-Laylin Lillian K. , Feldman Jessica L. , Stearns Tim 
Published: January 2025

AbstractCells reorganize in space and time to move and divide – complex behaviors driven by their internal cytoskeleton. While we have substantial knowledge of the molecular parts and rules of cytoskeletal assembly, we know less about how structures are remodeled, for example to interconvert centrioles from the ciliary base to the centrosome. To study this in an evolutionary context we use the chytrid fungus,Rhizoclosmatium globosum, a member of the zoosporic fungi which have centrioles and cilia, lost in other fungal lineages. Chytrids undergo reorganization of their microtubule cytoskeleton as they cycle from zoospore to multinucleated coenocyte. We use comparative bioinformatics, RNA sequencing, and expansion microscopy to map the microtubule cytoskeleton over the chytrid lifecycle. We find that when zoospores encyst, cilia are retracted into the cytoplasm and degraded, and centrioles detach but are protected from degradation. A shortened proximal centriole then forms the mitotic centrosome and ultimately elongates to form cilia at the end of the mitotic cycles, driven by a conserved transcriptional program. Thus, structural remodeling of the chytrid centriole is coupled temporally to ciliated stages rather than mitotic cycles, which may serve as a mechanism to tune microtubule organization to meet the needs of different lifecycle stages.
Mechanism of nascent chain removal by the Ribosome-associated Quality Control complex
Authors: Li Wenyan , Cahoon Talia , Shen Peter S. 
Published: January 2025

AbstractErrors during translation can cause ribosome stalling, leaving incomplete nascent chains attached to large ribosomal subunits1–5. Cells rely on the Ribosome-associated Quality Control (RQC) complex to recognize, process, and remove these partially synthesized proteins to maintain proteostasis. Despite its central role, the mechanisms by which the RQC complex orchestrates nascent chain processing and extraction have remained unclear. Here, we present a cryo-EM structure of the RQC complex from budding yeast, revealing how its core eukaryotic components function in nascent chain removal. We show that the Cdc48 protein extracting enzyme, along with its Ufd1-Npl4 adaptor, is recruited by the Ltn1 E3 ubiquitin ligase to extract ubiquitylated stalled peptides from the 60S ribosome. Additionally, we find that the Rqc1 component bridges the 60S ribosome with ubiquitin and Ltn1, facilitating the specific formation of K48-linked polyubiquitin chains on stalled peptides. These findings provide a structural and mechanistic framework for understanding how components of the RQC complex work together to remove faulty translation products from the ribosome, advancing our understanding of cellular protein quality control.
RBPscan: A Quantitative, In Vivo Tool for Profiling RNA-Binding Protein Interactions
Authors: Kretov Dmitry A. , Sanborn Owen , McIssac Thora , Park Elaine , Imrat  , Wu Samuel , Cifuentes Daniel 
Published: January 2025

SUMMARYRNA-binding proteins (RBPs) are essential regulators of gene expression at post-transcriptional level, yet obtaining quantitative insights into RBP-RNA interactionsin vivoremains a challenge. Here we developed RBPscan, a method that integrates RNA editing with massively parallel reporter assays (MPRAs) to profile RBP bindingin vivo. RBPscan fuses the catalytic domain of ADAR to the RBP of interest, using RNA editing of a recorder mRNA as a readout of binding events. We demonstrate its utility in zebrafish embryos, human cells, and yeast, where it quantifies binding strength, resolves dissociation constants, identifies high-specificity motifs for a variety of RBPs, and links binding affinities to their impact on mRNA stability. RBPscan also provides positional information of conserved and novel Pumilio-binding sites in lncRNANORAD. With its simplicity, scalability, and compatibility across systems, RBPscan offers a versatile tool for investigating RBP-RNA interactions and complements established methods for studying post-transcriptional regulatory networks.GRAPHICAL ABSTARCT
Tension-area relationship in compartmentalized crumpled plasma membrane: a mechanistic model and its implications
Authors: Tsaturyan Andrey K. 
Published: January 2025

AbstractThe plasma membrane is a liquid lipid bilayer containing both dissolved proteins and proteins anchoring the membrane to the underlying actin cortex. Membrane tension, a 2D analog of pressure in a 3D liquid, is believed to play a crucial role in organizing essential processes within cells and tissues. This, along with recent, conflicting data on the speed of membrane tension propagation, highlights the need for a comprehensive mechanical model to describe tension in the cortex-anchored plasma membrane as a function of transmembrane hydrostatic pressure difference and excess membrane area due to cortex contraction. In this study, we present a mechanical model of plasma membrane compartments, separated by “picket fences” of cortex-anchoring proteins permeable to lipids. Beyond hydrostatic pressure, the model incorporates the 2D osmotic pressure exerted by membrane-dissolved proteins. Our findings reveal that the tension-area relationship within a membrane compartment exhibits a seemingly paradoxical feature: in a specific range of membrane surface area, an increase in area leads to a rise in tension. We further model the tension-area relationship for an ensemble of membrane compartments, which exchange membrane area through shared borders, and discuss potential biological implications of this model.
Does white matter structure relate to hemispheric language lateralisation? A systematic review
Authors: Andrulyte Ieva , Demirkan Eszter , Branzi Francesca M. , Bonnett Laura J. , Keller Simon S. 
Published: January 2025

AbstractThe relationship between functional language lateralisation and diffusion MRI-based white matter metrics remains a subject of considerable interest and complexity. This systematic review aims to synthesise existing diffusion MRI studies examining white matter correlates of functional language dominance. Twenty-five studies were identified through searches of Web of Science, Scopus, and Ovid MEDLINE (search period: inception to 16th March 2023) involving adults with epilepsy, tumours, or healthy controls. The results suggest that while the arcuate fasciculus, particularly its fractional anisotropy (FA), is commonly associated with language lateralisation in clinical populations, the findings in healthy individuals are more variable, often influenced by factors such as handedness. Other white matter tracts, including the corpus callosum and uncinate fasciculus, showed less consistent associations with language dominance across studies. Interestingly, temporal lobe regions, especially those involved in semantic processing, exhibited stronger correlations with diffusion measures compared to areas associated with phonological tasks. Methodological inconsistencies, such as variability in sample selection, task design, and analytical techniques, were identified as significant challenges in comparing findings across studies. Future research should aim for larger, more diverse sample sizes, whole- brain approaches, and a wider range of fMRI tasks to better elucidate the role of white matter in language lateralisation. If regions of interest (ROI)-based studies are utilised, a more standardised approach to tract segmentation should be adopted to ensure consistency and improve comparability across studies.
Multi-center improvement in screening for pain that affects activities in adults with cerebral palsy
Authors: Bailes Amy F. , Noritz Garey H. , Wyeth Duncan O. , Lucas Elizabeth J. , Bates Elisabeth B. , Azizi Hana , Sarmiento Cristina A. , Thorpe Deborah E. , Nichols Stephen A. , Kreschmer Jodi , Wisniewski Stephen , Gannotti Mary ,   Cerebral Palsy Research Network
Published: January 2025

AbstractPurposeIncrease screening for pain in adults with cerebral palsy (CP) across three centers and examine factors associated with pain that affect activities.Materials and MethodsUsing the quality improvement (QI) infrastructure of the Cerebral Palsy Research Network (CPRN), we implemented interventions to improve screening at clinic visits for pain that affects activities for adults with CP. Three physicians from two CPRN centers performed interventions August 2021- June 2023 before spreading to a fourth physician at a third CPRN center October 2022. To track progress, we collected visit data cross sectionally every two weeks. Descriptive statistics, analysis of variance, and logistic regression evaluated relationships in a sample cohort of all visits after screening practices had been established.ResultsScreening improved from 42% at baseline to over 90%. After three months of sustained screening, we assessed 423 unique visits. Pain was reported at 185/423 (44%) of the visits. Of the 185 with pain reported, 100 (54%) reported pain that affected activities. Increasing age, female gender, and motor function were associated with pain (p<.001) and pain that affects activities (p<.01). Females reported pain 3.4 and pain that affects activity 2.2 times more than males.ConclusionQI methodology was successful at improving screening for pain that affects activities in adults with CP at clinic visits. Lower rates of pain were found (44%) than previous reports, with similar findings about pain affecting activities and associated characteristics. We propose continued screening with improvement in differentiating proxy vs self-report and including other domains of pain important to guide care such as location and chronicity.