bluuebunny/crossref_metadata_2025_split huggingface dataset:
Base-modified nucleotides mediate immune signaling in bacteria
Authors: Zeng Zhifeng , Hu Zeyu , Zhao Ruiliang , Rao Jikai , Mestre Mario Rodríguez , Liu Yanqiu , Liu Shunhang , Feng Hao , Chen Yu , He Huan , Chen Nuo , Zheng Jinshui , Peng Donghai , Luo Min , She Qunxin , Pinilla-Redondo Rafael , Han Wenyuan 
Published: January 2025

AbstractSignaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. While cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other messengers remains largely unexplored. Here, we reveal a bacterial anti-phage system that mediates immune signaling through nucleobase modification. Immunity is triggered by phage nucleotide kinases, which, combined with the system-encoded adenosine deaminase, produce deoxyinosine 5’-triphosphate (dITP) as immune messengers. The dITP signal activates downstream effector to mediate cellular NAD+depletion, resulting in population-level defense through the death of infected cells. To counteract immune signaling, phages deploy specialized enzymes that deplete cellular dAMP, the precursor of dITP messengers. Our findings uncover a nucleobase modification-based anti-phage signaling pathway, establishing noncanonical nucleotides as a new type of immune messengers in bacteria.
Horizontal gene transfers and terpene metabolism drive plant-fungal interaction inMarchantia polymorpha
Authors: El Mahboubi Karima , Beaulieu Chloé , Castel Baptiste , Libourel Cyril , Jariais Nathanaël , Amblard Emilie , van Beveren Fabian , Keller Jean , Martinez Yves , Nelson Jessica , Bonhomme Maxime , Jacquet Christophe , Delaux Pierre-Marc 
Published: January 2025

AbstractThe liverwortMarchantia polymorphahas emerged as a model for studying plant immunity in bryophytes, providing unique insights into conserved defense mechanisms across land plants. By contrast, Marchantia-specific immune mechanisms have not been explored. In this study, we investigated the genetic basis of quantitative resistance inM. polymorphaagainst the fungal pathogenColletotrichum nymphaeae, a naturally occurring compatible parasite. Through a combination of phenotypic, cytological and transcriptomic approaches, combined with genome-wide association studies (GWAS), we identified key defense-related genes and pathways. Transcriptomic analyses performed on two lines with contrasting suceptibilities to the pathogen revealed a strong overlap in immune responses betweenM. polymorphaand angiosperms, including the upregulation of PR proteins, transcription factors typically associated with biotic stresses, and enzymes involved in specialized metabolism. Leveraging the biological and genetic variability present in a collection of naturalM. polymorphaaccessions, highlight the role of horizontally transferred microbial-like terpene synthase (MTPSL) genes, which may contribute to the exceptional terpene diversity in liverworts and play a role in pathogen resistance. GWAS uncovered candidate loci associated with resistance traits, implicating both core immune components and specialized metabolic pathways. These results provide new insights into the specific molecular underpinnings of bryophyte immunity and underscore the evolutionary significance of horizontal gene transfer and specialized metabolites in shaping plant-pathogen interactions.
Direct observation of assembly and function of trigger responsive lipase biohybrids
Authors: Voutyritsa Errika , Sørensen Emily Winther , Oikonomou Athanasios , Lazou Thomai , Bushi Jonida , Christensen Sune M. , Velonia Kelly , Hatzakis Nikos S. 
Published: January 2025

AbstractProtein-polymer biohybrids mark a cutting edge in the creation of advanced materials designed for high performance under diverse conditions by combining the intrinsic stability and adaptability of synthetic polymers with the remarkable functionality and specificity of proteins. Despite the existence of stimuli responsive polymers, their potential for achieving precise, trigger responsive control over both the function and the assembly of protein-polymer biohybrids has yet to be fully attained. Here, we report the synthesis and thorough characterization of pH and temperature responsive lipase-polymer conjugates at both the supramolecular and the single molecule level. In contrast to conventional ensemble measurements performed in solution, we extensively characterized the stimuli triggered reversibility of the self-assembly of these lipase-based biohybrids and recorded the enzymatic activity at the fundamental level of individual nanoparticles. Our findings unexpectedly demonstrated that the stimuli responsive biohybrids exhibited not only a twofold increased enzymatic activity as compared to native lipases in certain cases but also maintained the trigger responsive control over enzymatic activity by temperature. Direct single particle recordings of biohybrid activity showed a correlation of the biohybrid size to catalytic activity, revealing individual enzymes to display higher activity in smaller nanoparticles. The biohybrids exhibit impressive long-term stability, in some cases almost 95% of the enzymatic activity as compared to ∼40-60% for native lipases after 1 year of storage. The improved stability and activity as compared to native enzymes accompanied with their triggered responsiveness highlight their significant potential for tightly controlled biocatalysis and sustainable industrial applications.
STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs
Authors: Lee Hye Kyung , Chen Jichun , Philips Rachael L. , Lee Sung-Gwon , Feng Xingmin , Wu Zhijie , Liu Chengyu , Schultz Aaron B. , Dalzell Molly , Birnbaum Foster , Sexton Joel A. , Keating Amy E. , O’Shea John J. , Young Neal S. , Villarino Alejandro V. , Furth Priscilla A. , Hennighausen Lothar 
Published: January 2025

SummarySTAT5B is a vital transcription factor for lymphocytes. Here, function of two STAT5B mutations from human T cell leukemias: one substituting tyrosine 665 with phenylalanine (STAT5BY665F), the other with histidine (STAT5BY665H) was interrogated.In silicomodeling predicted divergent energetic effects on homodimerization with a range of pathogenicity. In primary T cellsin vitroSTAT5BY665Fshowed gain-of-function while STAT5BY665Hdemonstrated loss-of-function. Introducing the mutation into the mouse genome illustrated that the gain-of-functionStat5bY665Fmutation resulted in accumulation of CD8+effector and memory and CD4+regulatory T-cells, altering CD8+/CD4+ratios. In contrast, STAT5BY665H‘knock-in’ mice showed diminished CD8+effector and memory and CD4+regulatory T cells. In contrast to wild-type STAT5, the STAT5BY665Fvariant displayed greater STAT5 phosphorylation, DNA binding and transcriptional activity following cytokine activation while the STAT5BY665Hvariant resembled a null. The work exemplifies how joiningin silicoandin vivostudies of single nucleotides deepens our understanding of disease-associated variants, revealing structural determinants of altered function, defining mechanistic roles, and, specifically here, identifying a gain-of function variant that does not directly induce hematopoietic malignancy.
The impact of musical expertise on disentangled and contextual neural encoding of music revealed by generative music models
Authors: Mischler Gavin , Li Yinghao Aaron , Bickel Stephan , Mehta Ashesh D. , Mesgarani Nima 
Published: January 2025

AbstractMusic perception involves the intricate processing of individual notes and their contextual relationships within a piece. However, how the brain encodes and organizes these features, particularly in relation to musical expertise, remains unclear. Using noninvasive and invasive electrophysiological recordings alongside generative music models, we reveal that musicians exhibit neural encoding that is more attuned to the separation and integration of complex musical structures, with a pronounced left-hemispheric bias compared to non-musicians. Invasive recordings further highlight a hierarchical and spatially organized representation of musical features and context across brain regions. These findings advance our understanding of how the brain processes music and the role of musical training in shaping auditory cognition.
Biofabrication of spatially organized temporo-mandibular fibrocartilage assembloids
Authors: Dufour Alexandre , Essayan Lucie , Kim Beomjoon , Salles Vincent , Marquette Christophe 
Published: January 2025

AbstractThe combination of mesenchymal stem cell (MSC) spheroids and polymeric scaffolds has been actively explored for engineering organized hyaline cartilage; however, its application to other types of cartilage remains under-explored. The temporo-mandibular joint (TMJ) fibrocartilage is a highly stratified tissue whose recapitulation remains challenging. In this study, the shape and growth orientation of assembloids were controlled by seeding early mature human adipose-derived MSC spheroids into polymeric scaffolds with a dual architecture of micron-scale fibers. This results in flattened asymmetric tissues with a single-sided articular surface. Structurally, the engineered fibrocartilage mimicked the histotypical organization observed in the native human condylar fibrocartilage, notably featuring a thick fibrous zone with flattened cells. Native-like distribution of general extracellular matrix (ECM) components, including glycosaminoglycans and total collagens, and ECM-specific components, such as type I and II collagens, aggrecan core protein, and fibronectin, were observed. Collagen organization, as demonstrated by polarized light microscopy and scanning electron microscopy at the fibril level, was also found to be similar to that of native human tissue. Zonal-dependent micromechanical properties were identified in both the engineered and native tissues, although lower mechanical properties were observed in the fibrous zone of the engineered tissue. This work provides further evidence that the combination of MSC spheroids and micron-sized fiber polymeric scaffolds is a versatile approach for engineering stratified cartilage and a promising strategy for engineering biomimetic fibrocartilage grafts for TMJ reconstruction.
A Prediction Method of Land Use Type Evolution Based on Long and Short-Term Memory Networks—Taking Gansu Province as an Example
Authors: Zhang Shiqi , Cao Chuhui 
Published: January 2025

AbstractIn the context of escalating global climate change and human activities, understanding the driving mechanisms behind land use change and predicting future trends is crucial. This study takes Gansu Province as a case, using land use type data from 1990 to 2020 to construct a Long Short-Term Memory (LSTM) model to predict land use changes over the next decade (2021–2030). The results indicate that land use types in Gansu Province exhibit significant dynamic changes, with forest area continuously increasing, built-up land rapidly expanding, and areas of unused land and grassland significantly decreasing. These changes reflect the combined effects of ecological protection policies, urbanization, and land development. The model’s predictions suggest that built-up land has absorbed substantial areas of unused land, grassland, and cultivated land, with accelerated urbanization. Forest area growth is attributed to the implementation of ecological restoration policies, while grassland and water areas show fluctuating changes, and the area of unused land continues to decrease. The findings not only provide data support for land resource management and ecological protection, but also offer scientific evidence for the formulation of sustainable land use policies, which can serve as an important reference for the sustainable use and management of land resources in Gansu Province and similar regions.
Parvovirus B19 genomic DNA concentrations in wastewater solids are associated with community infections
Authors: Zulli Alessandro , Linfield Rebecca Y. , Duong Dorothea , Shelden Bridgette , Boehm Alexandria B. 
Published: January 2025

AbstractWe assessed concentrations of parvovirus B19 DNA from two wastewater treatment plants in a county with a known outbreak in 2024. Wastewater viral concentrations correlated significantly with clinical cases, demonstrating wastewater’s potential for tracking parvovirus B19 infections. Peaks in wastewater concentrations were aligned with the peak in hydrops fetalis diagnoses.
Cryo-EM structures of engineered Shiga toxin-based immunogens capable of eliciting neutralizing antibodies with therapeutic potential against Hemolytic Uremic Syndrome
Authors: Cristófalo Alejandro Ezequiel , Sharma Arvind , Cerutti María Laura , Sharma Kedar , Melero Roberto , Pardo Romina , Goldbaum Fernando Alberto , Borgnia Mario , Zylberman Vanesa , Otero Lisandro Horacio 
Published: January 2025

ABSTRACTShiga toxin-producingEscherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a serious disease that causes renal failure predominantly in children. Despite its significant impact, there are currently no licensed vaccines or effective therapies available. The B subunits of Shiga toxins 1 and 2 (Stx1B and Stx2B) are suitable targets for developing neutralizing antibodies, but their pentameric assembly is unstable when isolated from the whole toxin. Taking advantage of the oligomeric symmetry shared between Stx1B and Stx2B with the lumazine synthase fromBrucellaspp. (BLS), we have previously engineered the chimeric toxoids BLS-Stx1B and BLS-Stx2B as immunogens to generate therapeutic equine polyclonal antibodies. The resulting product (INM004) has successfully passed phases 1 and 2 clinical trials, and a phase 3 has been launched in Argentina and seven European countries. In this work, we present the cryo-EM structures of BLS-Stx1B and BLS-Stx2B, which confirm that these engineered immunogens effectively stabilize the StxB pentamers. Moreover, our results reveal that both chimeric constructs present high flexibility at their extremes, corresponding to motions of the StxBs with respect to the BLS core. Additionally, we present structural evidence of the interaction between the chimeras and polyclonal Fab (pFab) fragments derived from INM004, demonstrating that the elicited neutralizing antibodies block most of the interaction surface of the toxins with their cellular receptors. These findings further validate this promising antibody-based therapy for mitigating STEC-HUS and demonstrate that the BLS-Stx1B and BLS-Stx2B chimeras are potential candidates for developing a human vaccine.
Evidence of flowering time advance in blue lupin (Lupinus angustifolius) in the last decades revealed by herbarium data and citizen science databases
Authors: Jiménez – López F.J. , Lara – Romero C. , Iriondo J.M. , Rubio Teso M.L. , García – Fernández A 
Published: January 2025

AbstractRapid adaptation to climate change in plants manifests through genetic modifications, epigenetic changes, or species-microbiome interactions, with short-living species having a greater potential for adaptation. The integration of historical collection data with modern databases improves our ability to study plant phenology and distribution shifts in response to global change. This study evaluates changes in the flowering phenology and vernalization requirements ofLupinus angustifoliuspopulations across the Iberian Peninsula, assessing the effectiveness of diverse data sources. Using herbarium specimens and field photographs, we compiled flowering data and estimated flowering peaks. Thermal time and vernalization requirements were estimated using recorded flowering stages and high-resolution climate data. Analyses revealed a progressive advancement inL. angustifoliusflowering in the last 60 years. Latitude and elevation emerged as significant influencing factors, with greater shifts observed at lower latitudes and elevations. Notably, plants now flower with fewer vernalization days, and higher thermal time, particularly at lower elevations. The adaptive responses of plants to global change are intricate and dynamic. Phenological advancement in flowering appears to be a key strategy for coping with environmental alterations, facilitating survival and reproduction through the interplay of genotype, phenotype, and environment, as well as existing genetic diversity. In this context, historical records and long-term monitoring prove invaluable for assessing the efficacy and pace of these adaptive processes. To improve our understanding of plant adaptation in the context of climate change, it is essential to synthesize diverse data sources and maintain ongoing collection efforts.
Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing
Authors: Dave Arjun , Ye Shuer , Bätz Leona Rahel , Lan Xiaqing , Jacobs Heidi I.L. , Ziaei Maryam 
Published: January 2025

AbstractInterpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brain’s main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, the LC supports adapting to cognitive demands and resolving conflicting cues from environment, particularly in later life. Previous research suggests that the LC interacts with the prefrontal cortex during high-conflict tasks. However, whether LC activity and its connectivity with the PFC support emotional ambiguity processing and contributes to emotional well-being in healthy aging remains unclear. To address this gap, we used 7T-MRI to examine LC function in 75 younger (25.8±4.02years, 35females) and 69 older adults (71.3±4.1 years, 35females) during facial emotion-recognition task morphed with varying ambiguity: anchor (unambiguous happy or fearful), intermediate- ambiguity (30% happy–70% fearful and 40%-happy–60% fearful expressions, in either direction), and absolute-ambiguity (50% happy-fearful). Behaviorally, participants had longer response times and lower confidence in the absolute-ambiguity condition, while older adults perceived ambiguous faces as happy more frequently than younger adults. Neuroimaging results revealed older adults exhibited greater LC activity and enhanced connectivity with dorsolateral PFC (dlPFC) during absolute-ambiguity compared to younger adults. This heightened connectivity in older adults was linked to better emotional resilience and mental well-being. These findings suggest greater LC activity supports managing cognitively demanding tasks, while enhanced LC-dlPFC connectivity helps maintain emotional well- being, underscoring the importance of this neural pathway for healthy aging.Significance StatementUnderstanding how the brain adapts to cognitive and emotional demands with age is key to promoting healthy aging. This study examined whether the locus coeruleus (LC), a brain region critical for regulating attention and arousal, undergoes adaptive changes with age, especially during emotional ambiguity task. Using ultra-high-field imaging, we explored younger and older adults recognize facial expressions with varying ambiguity levels. Our findings indicated that compared to young, older adults showed heightened LC activity and LC-dorsolateral prefrontal cortex (dlPFC) connectivity when processing absolute-ambiguous facial expressions, with enhanced connectivity linked to improved mental well-being. These results suggest higher LC activity supports cognitive demands of ambiguity processing with LC- dlPFC connectivity promoting emotional well-being and resilience, offering insights into mechanisms underlying healthy aging.
High-speed 10-plex DNA-PAINT with a larger sequence repertoire
Authors: Banerjee Abhinav , Srivastava Mansi , Vidwath Vedanth Shree , Ganji Mahipal 
Published: January 2025

AbstractDNA-Points Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) enables multiplexed super-resolution imaging of biological samples. We expand the repertoire of speed-optimized DNA sequences for DNA-PAINT imaging to facilitate the molecular-resolution imaging of up to ten targets in a sequential manner. These imager sequences showcase a range of binding kinetics, providing the flexibility to select optimal sequences for specific applications. We demonstrate the application of twelve speed-optimized imager sequences for multiplexed super-resolution imaging of the microtubular network and Nuclear Lamins in the cellular context. We anticipate that the ability to image as many as ten targets using the simple Exchange-PAINT strategy at accelerated speed will drive its further adoption for diverse cellular imaging applications.
Reduced signatures of gene duplication and non-random gene organization in shaping stage-specific patterns of gene expression across a relatively simple life cycle
Authors: DuBose James G. , Morran Levi T. 
Published: January 2025

AbstractComplex eukaryotes generally experience some degree of ecological transition as they develop, which is usually accompanied by the expression of different traits across their ontogeny. Theory suggests the evolution of differentiation between life stages is facilitated by the expression of different genes at different points throughout ontogeny, which alleviates pleiotropic evolutionary constraints. Therefore, ascertaining what contributes to specialized patterns of gene expression across ontogeny is fundamental to understanding the evolution of ontogenetic complexity. Expression divergence between duplicate genes and gene organization on chromosomes have been identified as important features of relatively complex ontogenies. Therefore, one could predict that their link to transcriptional specialization across ontogeny may be weaker in relatively simpler life cycles. Here, we investigated the links between gene duplication, gene organization, and stage-specific patterns of expression across the relatively simpleCaenorhabditis eleganslife cycle. We found that signatures of stage-biased chromosomal regions were weaker inC. elegansthan what has been previously described in organisms with more complex ontogenies. Furthermore, we found the extent that duplicate genes varied in ontogenetic expression pattern was more constrained inC. elegans. Overall, our findings add to a body of evidence that suggests a link between gene duplication and gene organization and the evolution of complex ontogenies.
Spatial transcriptomics exploration of the primary neuroblastoma microenvironment unveils novel paracrine interactions
Authors: Siaw Joachim T. , Merseburger Peter , Borenäs Marcus , Jansson Caroline , Karlson Jenny , Claeys Arne , Jennische Eva , Lind Dan E. , Gisselsson Nord David , Palmer Ruth H. , Van den Eynden Jimmy 
Published: January 2025

ABSTRACTHigh-risk neuroblastomas exhibit a high degree of intratumoral heterogeneity. Single-cell RNA sequencing has greatly improved our understanding of these tumors, but the method lacks cellular tissue context and spatial information about local signaling dynamics. To address this gap, we profiled untreated and chemotherapy-treated high-risk neuroblastomas from 2 patients using spatial transcriptomics. We confirmed the transcriptional and cellular heterogeneous nature of the neuroblastoma microenvironment and identified several unique spatial niches and patterns. In one of the treated tumors, a spatially constrained cluster of undifferentiated and 11p-gained cancer cells was identified, surrounded by a rim of macrophages. A signaling interaction between the chemokineCCL18and its receptorPITPNM3was predicted between these cells and we experimentally demonstrated thatCCL18increases neuroblastoma cell migration. In the other tumor, we identified a stromal cluster with high transcriptional similarity to the adrenal cortex. These adrenocortical-like cells expressed the ALK ligandALKAL2and were predicted to communicate with neighboringALKexpressing cancer cells. We demonstrated a unique developmental pattern of adrenal medulla-specific expression ofALKand adrenocortical-specific expression ofALKAL2, suggesting a role of these signaling interactions in neuroblastoma carcinogenesis.