bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative metabolomics of wild and cultivatedTaxus cuspidata: insights into metabolic diversity and environmental adaptability
Authors: Wang Dandan , Zhang Yanwen 
Published: July 2024

AbstractTaxus cuspidatais a well-known gymnosperm with great ornamental and medicinal value. The study aims to reveal the metabolic differences between wild and cultivated species ofT. cuspidata, and to analyze the genetic and ecological factors behind these differences. This study conducted a comparative metabolomics analysis of wild and cultivatedT. cuspidatabased on LC-MS/MS technology. The results showed: (1) A total of 7030 metabolites were identified, primarily including flavonoids, organic acids, phenolic acids, amino acids and their derivatives, lipids, and alkaloids, among others; (2) 2381 differential metabolites were confirmed: 949 higher in cultivated species and 1432 higher in wild species, which suggesting wild species have more advantageous metabolites. (3) Through KEGG annotation, 20 significant metabolic pathways were identified, with sugar metabolism, photosynthesis, and sulfur metabolism were significantly higher in wild species. In contrast, pathways related to most amino acids and their derivatives, flavonoids, terpenoids, polyphenols, alkaloids, and plant hormones were significantly higher in cultivated species. In conclusion, the wild species are inferior to cultivated species in terms of drought resistance, growth rate, and medicinal value for cancer treatment. However, the advantage of wild species lies in their significantly higher diversity of upregulated secondary metabolites due to their rich genetic resources, which exhibit greater metabolic diversity and environmental adaptability, which enhances their survival capability. Furthermore, the wild species exhibit significantly higher efficiency in photosynthesis and sugar metabolism compared to cultivated species, enabling them to better withstand low-temperature stress. This study has provided the direction for research into the mechanisms of stress resistance inT. cuspidataand has also established a theoretical basis for formulating scientifically and reasonable conservation strategies for wild species.
Integrative, high-resolution analysis of single cells across experimental conditions with PARAFAC2
Authors: Ramirez Andrew , Orcutt-Jahns Brian T. , Pascoe Sean , Abraham Armaan , Remigio Breanna , Thomas Nathaniel , Meyer Aaron S. 
Published: July 2024

AbstractEffective tools for exploration and analysis are needed to extract insights from large-scale single-cell measurement data. However, current techniques for handling single-cell studies performed across experimental conditions (e.g., samples, perturbations, or patients) require restrictive assumptions, lack flexibility, or do not adequately deconvolute condition-to-condition variation from cell-to-cell variation. Here, we report that the tensor decomposition method PARAFAC2 (Pf2) enables the dimensionality reduction of single-cell data across conditions. We demonstrate these benefits across two distinct contexts of single-cell RNA-sequencing (scRNA-seq) experiments of peripheral immune cells: pharmacologic drug perturbations and systemic lupus erythematosus (SLE) patient samples. By isolating relevant gene modules across cells and conditions, Pf2 enables straightforward associations of gene variation patterns across specific patients or perturbations while connecting each coordinated change to certain cells without pre-defining cell types. The theoretical grounding of Pf2 suggests a unified framework for many modeling tasks associated with single-cell data. Thus, Pf2 provides an intuitive universal dimensionality reduction approach for multi-sample single-cell studies across diverse biological contexts.HighlightsPARAFAC2 enables tensor-based analysis of single-cell experiments across conditions.PARAFAC2 separates condition-specific effects from cell-to-cell variation.PARAFAC2 provides intuitive isolation of patterns into condition-, cell-, and gene-specific patterns.
Glucocorticoids desensitize hypothalamic CRH neurons to norepinephrine and somatic stress activation via rapid nitrosylation-dependent regulation of α1 adrenoreceptor trafficking
Authors: Weiss Grant L , Harrison Laura M. , Jiang Zhiying , Nielsen Alyssa M. , Feygin Maximillian S. , Nguyen Sandy , Tirrell Parker S. , Tasker Jeffrey 
Published: July 2024

SummaryNoradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive for somatic stress activation of the hypothalamic-pituitary-adrenal (HPA) axis. We showed that glucocorticoids rapidly desensitize CRH neurons to norepinephrine and suppress inflammation-induced HPA activation via a glucocorticoid receptor- and endocytosis-dependent mechanism. Here, we show that α1 adrenoreceptor (ARα1) trafficking is regulated by convergent glucocorticoid and nitric oxide synthase signaling mechanisms. Live-cell imaging of ARα1b-eGFP-expressing hypothalamic cells revealed rapid corticosterone-stimulated redistribution of internalized ARα1 from rapid recycling endosomes to late endosomes and lysosomes via a nitrosylation-regulated mechanism. Proximity assay demonstrated interaction of glucocorticoid receptors with ARα1b and β-arrestin, and showed corticosterone blockade of norepinephrine-stimulated ARα1b/β-arrestin interaction, which may prevent ARα1b from entering the rapid recycling endosomal pathway. These findings demonstrate a rapid glucocorticoid regulation of G protein-coupled receptor trafficking and provide a molecular mechanism for rapid glucocorticoid desensitization of noradrenergic signaling in CRH neurons.
White matter connections of human ventral temporal cortex are organized by cytoarchitecture, eccentricity, and category-selectivity from birth
Authors: Kubota Emily , Yan Xiaoqian , Tung Sarah , Fascendini Bella , Tyagi Christina , Duhameau Sophie , Ortiz Danya , Grotheer Mareike , Natu Vaidehi S. , Keil Boris , Grill-Spector Kalanit 
Published: July 2024

AbstractCategory-selective regions in ventral temporal cortex (VTC) have a consistent anatomical organization, which is hypothesized to be scaffolded by white matter connections. However, it is unknown how white matter connections are organized from birth. Here, we scanned newborn to 6-month-old infants and adults to determine the organization of the white matter connections of VTC. We find that white matter connections are organized by cytoarchitecture, eccentricity, and category from birth. Connectivity profiles of functional regions in the same cytoarchitectonic area are similar from birth and develop in parallel, with decreases in endpoint connectivity to lateral occipital, and parietal, and somatosensory cortex, and increases to lateral prefrontal cortex. Additionally, connections between VTC and early visual cortex are organized topographically by eccentricity bands and predict eccentricity biases in VTC. These data show that there are both innate organizing principles of white matter connections of VTC, and the capacity for white matter connections to change over development.
Age-related myelin deficits in the auditory brain stem contribute to cocktail-party deficits
Authors: Poleg Shani , Li Ben-Zheng , Sergison Matthew , Ridenour Matthew , Hughes Ethan G. , Tollin Daniel , Klug Achim 
Published: July 2024

SUMMARYAge-related hearing loss consists of both peripheral and central components and is an increasing global health concern. While peripheral hearing loss is well understood, central hearing loss— age-related changes in the central auditory pathways resulting in a listener’s inability to process sound correctly —remains poorly understood. In this study, we focus on the pathway from the cochlear nucleus to the medial nucleus of the trapezoid body (MNTB), which depends on heavily myelinated axons for microsecond-level temporal precision required for sound localization.Using a combination of auditory brainstem response recordings (ABR), advanced light and electron microscopy, and behavioral testing with prepulse inhibition of the acoustic startle response (PPI) we identified a correlation between oligodendrocyte loss, abnormal myelination in MNTB afferents, altered ABR wave III morphology indicating MNTB dysfunction, and deficits in spatial hearing behaviors in aging Mongolian gerbils.These findings provide a mechanistic explanation of how demyelination contributes to age-related dysfunction in the auditory brainstem’s sound localization pathway.
Amyloid peptide – synthetic polymer blends with enhanced mechanical and biological properties
Authors: Wang Xianjun , Mondal Malay , Jankoski Penelope E. , Kemp Lisa K. , Clemons Tristan D. , Rangachari Vijayaraghavan , Morgan Sarah E. 
Published: July 2024

ABSTRACTInterest in utilizing amyloids to develop biomaterials is increasing due to their potential for biocompatibility, unique assembling morphology, mechanical stability, and biophysical properties. However, challenges include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials. In this work, two decapeptides with fibrillar and globular morphologies were selected, blended with poly(ethylene oxide), and fabricated into composite mats via electrospinning. Notable enhancements in mechanical properties were observed, attributed to the uniform distribution of the decapeptide assemblies within the PEO matrix. Morphological differences, such as the production of thinner nanofibers, are attributed to the increased conductivity from the zwitterionic nature of the decapeptides. Blend rheology and post-processing analysis revealed how processing might affect the amyloid aggregation and secondary structure of the peptides. Both decapeptides demonstrated good biocompatibility and strong antioxidant activity, indicating their potential for safe and effective use as biomaterials. By evaluating these interdependencies, this research lays the foundation for understanding the structure-property-processing relationships of peptide-polymer blends and highlights the strong potential for developing applications in biotechnology.
Formation of stress granules and non-canonical survival responses in arsenite-exposed cells
Authors: Hirano Seishiro , Udagawa Osamu , Kanno Sanae 
Published: July 2024

AbstractThe concentration-dependent decrease in viable cells is a well-documented phenomenon in cytotoxicity assays for most toxic substances. We report that arsenite (As3+), a widely recognized oxidative toxicant, exhibited lower cytotoxic effects at 300 µM compared to 100 µM As3+in CHO-K1 and Jurkat cells. Formation of stress granules (SGs), which appear in the cytoplasm shortly after exposure to hypertonicity, heat shock, and high concentrations of As3+is considered as a pro-survival cellular event. We hypothesized that unusual cytotoxicity profile of As3+could be attributed to SG formation. In both CHO-K1 and Jurkat cells stably expressing GFP-tagged G3BP1, SGs were more rapidly and distinctly induced by 300 µM As3+than 100 µM As3+. Other toxic metals and a metalloid such as Cd2+, Cu2+, Ag+, and Se4+did not clearly induce SG formation and instead reduced the viability in a concentration-dependent manner. Exposure to As3+led to phosphorylation of eIF2α, a key regulator of polysome stability and a hallmark of SG formation. Depletion of intracellular glutathione (GSH) increased the susceptibility of cells to As3+, highlighting its role in cellular defense mechanisms. Exposure to As3+activated small ubiquitin-like modifier (SUMO) which is implicated in phase separation. However, neither depletion of GSH nor overexpression of SUMO contributed As3+-induced SG formation. Consistently, THP-1 and HL60 cells exposed to As3+also exhibited non-canonical cytotoxic features, albeit at higher concentrations (1 mM). These findings underscore the need for further mechanistic investigations into As3+-induced SG formation, given that As3+is a promising anti-cancer agent, and resistance of tumor cells to As3+is a critical issue.
CaLMPhosKAN: Prediction of General Phosphorylation Sites in Proteins via Fusion of Codon-Aware Embeddings with Amino Acid-Aware Embeddings and Wavelet-based Kolmogorov–Arnold Network
Authors: Pratyush Pawel , Carrier Callen , Pokharel Suresh , Ismail Hamid D. , Chaudhari Meenal , KC Dukka B. 
Published: July 2024

AbstractThe mapping from codon to amino acid is surjective due to the high degeneracy of the codon alphabet, suggesting that codon space might harbor higher information content. Embeddings from the codon language model have recently demonstrated success in various downstream tasks. However, predictive models for phosphorylation sites, arguably the most studied Post-Translational Modification (PTM), and PTM sites in general, have predominantly relied on amino acid-level representations. This work introduces a novel approach for prediction of phosphorylation sites by incorporating codon-level information through embeddings from a recently developed codon language model trained exclusively on protein-coding DNA sequences. Protein sequences are first meticulously mapped to reliable coding sequences and encoded using this encoder to generate codon-aware embeddings. These embeddings are then integrated with amino acid-aware embeddings obtained from a protein language model through an early fusion strategy. Subsequently, a window-level representation of the site of interest is formed from the fused embeddings within a defined window frame. A ConvBiGRU network extracts features capturing spatiotemporal correlations between proximal residues within the window, followed by a Kolmogorov-Arnold Network (KAN) based on the Derivative of Gaussian (DoG) wavelet transform function to produce the prediction inference for the site. We dub the overall model integrating these elements as CaLMPhosKAN. On independent testing with Serine-Threonine (combined) and Tyrosine test sets, CaLMPhosKAN outperforms existing approaches. Furthermore, we demonstrate the model’s effectiveness in predicting sites within intrinsically disordered regions of proteins. Overall, CaLMPhosKAN emerges as a robust predictor of general phosphosites in proteins. CaLMPhosKAN will be released publicly soon.
The origin of septin ring size control in budding yeast
Authors: Kukhtevich Igor , Persson Sebastian , Padovani Francesco , Schneider Robert , Cvijovic Marija , Schmoller Kurt M. 
Published: July 2024

AbstractThe size of organelles and cellular structures needs to be tightly controlled and adjusted to the overall cell size to ensure cell function. A prominent example of a self-assembly process forming a structure whose size scales with cell size is Cdc42-driven cell polarization and subsequent septin ring formation inSaccharomyces cerevisiae. Despite extensive research, the mechanisms that determine Cdc42 cluster and septin ring size are still unclear. Combining computational modeling, live-cell imaging and genetic manipulations, we show here that positive feedback in the polarization pathway, together with the amount of polarity proteins increasing with cell size, can account for the increase of the Cdc42 cluster area with cell size, and as a consequence also the scaling of the septin ring diameter. We demonstrate that inbni1Δcells, which have a larger septin ring compared to wild-type cells but a similarly sized Cdc42-GTP cluster, disruption of F-actin cable assembly and polarization toward the bud site results in diffuse exocytosis, causing septin ring enlargement. Furthermore, we find that in cells with impaired negative feedback in the polarization pathway, the Cdc42-GTP cluster area expands compared to wild-type cells, while the septin ring diameter remains mostly unchanged. This decoupling can be partially explained by a high recruitment rate of septin via polarity factors. Taken together, we provide insights into the origin of septin ring size control, in particular the scaling with cell volume, by integrating new experimental findings and mechanistic models of budding yeast polarization.
Distributed Collaboration for Data, Analysis Pipelines, and Results in Single-Cell Omics
Authors: Hutton Alexandre , Ai Lizhuo , Meyer Jesse G. 
Published: July 2024

AbstractSingle-cell omics data analysis pipelines are complicated to design and difficult to share or reproduce. We describe a web platform that enables no-code analysis pipeline design, simple computing via the Open Science Grid, and sharing of entire data analysis pipelines, their input data, and interactive results. We expect this platform to increase the accessibility and reproducibility of single-cell omics.
Evolution of the RNA alternative decayciselement into a high-affinity target for the immunomodulatory protein Roquin
Authors: Tants Jan-Niklas , Friedrich Katharina , Neumann Jasmina , Schlundt Andreas 
Published: July 2024

ABSTRACTRNAciselements play pivotal roles in regulatory processes, e.g. in transcriptional and translational regulation. Two stem-loopedciselements, the constitutive and alternative decay elements (CDE and ADE, respectively) are shape-specifically recognized in mRNA 3’ untranslated regions (UTRs) by the immune-regulatory protein Roquin. Roquin initiates mRNA decay and contributes to balanced transcript levels required for immune homeostasis. While the interaction of Roquin with several CDEs is described, our knowledge about ADE complex formation is limited to the mRNA ofOx40, a gene encoding for a T-cell co-receptor. TheOx403’UTR comprises both a CDE and ADE, each sufficient for Roquin-mediated control. Opposed to highly conserved and abundant CDE structures, ADEs are rarer, but predicted to exhibit a greater structural heterogeneity. This raises the question how and when two structurally distinctciselements evolved as equal target motifs for Roquin. Using an interdisciplinary approach we here monitor the evolution of sequence and structure features of theOx40ADE across species. We designed RNA variants to probe en-detail determinants steering Roquin-RNA complex formation. Specifically, those reveal the contribution of a second RNA-binding interface of Roquin for recognition of the ADE basal stem region. In sum, our study sheds light on how the conserved Roquin protein selected ADE-specific structural features to evolve a second high-affinity mRNA targetcis-element relevant for adaptive immune regulation. As our findings also allow expanding the RNA target spectrum of Roquin, the approach can serve a paradigm for understanding RNA-protein specificity through back-tracing the evolution of the RNA element.
Pharyngeal neuronal mechanisms governing sour taste perception inDrosophila melanogaster
Authors: Shrestha Bhanu , Sang Jiun , Rimal Suman , Lee Youngseok 
Published: July 2024

AbstractSour taste, which is elicited by low pH, may serve to help animals distinguish appetitive from potentially harmful food sources. In all species studied to date, the attractiveness of oral acids is contingent on concentration. Many carboxylic acids are attractive at ecologically relevant concentrations but become aversive beyond some maximal concentration. Recent work found thatDrosophilaionotropic receptors IR25a and IR76b expressed by sweet-responsive gustatory receptor neurons (GRNs) in the labellum, a peripheral gustatory organ, mediate appetitive feeding behaviors toward dilute carboxylic acids. Here, we disclose the existence of pharyngeal sensors inD. melanogasterthat detect ingested carboxylic acids and are also involved in the appetitive responses to carboxylic acids. These pharyngeal sensors rely on IR51b, IR94a, and IR94h, together with IR25a and IR76b, to drive responses to carboxylic acids. We then demonstrate that optogenetic activation of eitherIr94a+orIr94h+GRNs promotes an appetitive feeding response, confirming their contributions to appetitive feeding behavior. Our discovery of internal pharyngeal sour taste receptors opens up new avenues for investigating the internal sensation of tastants in insects.
Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus
Authors: Jabłońska Jadwiga , Wiera Grzegorz , Mozrzymas Jerzy W. 
Published: July 2024

AbstractThe brain’s extracellular matrix (ECM) is crucial for neural circuit functionality, synaptic plasticity, and learning. While the role of the ECM in excitatory synapses has been extensively studied, its influence on inhibitory synapses, particularly on GABAergic long-term plasticity, remains poorly understood. This study aims to elucidate the effects of ECM components on inhibitory synaptic transmission and plasticity in the hippocampal CA1 region. We focus on the roles of chondroitin sulfate proteoglycans (CSPGs) and hyaluronic acid in modulating inhibitory postsynaptic currents (IPSCs) at two distinct inhibitory synapses formed by somatostatin (SST)-positive and parvalbumin (PV)-positive interneurons onto pyramidal cells (PCs). Using optogenetic stimulation in brain slices, we observed that acute degradation of ECM constituents by hyaluronidase or chondroitinase-ABC did not affect basal inhibitory synaptic transmission. However, short-term plasticity, particularly burst-induced depression, was enhanced at PV→PC synapses following enzymatic treatments. Long-term plasticity experiments demonstrated that CSPGs are essential for NMDA-induced iLTP at SST→PC synapses, whereas the digestion of hyaluronic acid by hyaluronidase impaired iLTP at PV→PC synapses. This indicates a synapse-specific role of CSPGs and hyaluronic acid in regulating GABAergic plasticity. Additionally, we report the presence of cryptic GABAergic plasticity at PV→PC synapses induced by prolonged NMDA application, which became evident after CSPG digestion and was absent under control conditions. Our results underscore the differential impact of ECM degradation on inhibitory synaptic plasticity, highlighting the synapse-specific interplay between ECM components and specific GABAergic synapses. This offers new perspectives in studies on learning and critical period timing.
Efficient generation of CAR NK cells from human umbilical cord blood CD34+stem and progenitors for democratizing affordable immunotherapy
Authors: Li Jianhuan , Wang Yao , Zheng Xiujuan , Lin Yunqing , Weng Qitong , Liu Xiaofei , Geng Yang , Wu Hongling , Liu Lijuan , Peng Huan , Wu Bingyan , Huang Dehao , Xia Chengxiang , Wang Tongjie , Zhang Mengyun , Du Xin , Zeng Hui , Dong Fang , Zhang Yingchi , Zhu Xiaofan , Hu Fangxiao , Wang Jinyong 
Published: July 2024

AbstractChimeric antigen receptor (CAR) natural killer cells (CAR NK) cells, leveraging safety and not requiring HLA match in adoptive infusion, have emerged as promising alternative cells to CAR-T cells for immunotherapies. High and multiple doses of CAR NK cell infusions are essential to maintain therapeutic efficacy in clinical trials. This requires efficient methods for generating large-scale CAR NK cells and significantly reducing CAR engineering costs. In this study, we develop a three-step strategy to generate highly high yields of induced NK (iNK) and CAR iNK cells from human umbilical cord blood CD34+hematopoietic stem and progenitor cells (CD34+HSPCs). Starting from a single umbilical cord blood CD34+HSPC, our reliable method efficiently produces 14-83 million mature iNK cells or 7-32 million CAR iNK cells with high expression levels of CD16 and zero T cell contaminations. Introducing CAR expression elements at the HSPC level reduces the quantities of CAR pseudoviruses to 1 / 140.000 - 1 / 600,000 compared to engineering CARs in mature NK cells. The iNK and CAR iNK cells, including fresh cells and thawed cells from cryopreserved conditions, demonstrate remarkable tumoricidal activities against various human cancer cells and significantly prolong the survival of human tumor-bearing animals. The high yields of CAR NK cells and negligible costs of CAR engineering of our method support the broad applications of CAR NK cells for treating cancer patients.