bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection of Bone-Targeting Peptides for Therapeutic Intervention: An In Vivo Evaluation and Comparison Study
Authors: Stellpflug Austin , Joshi Amit , Wang Shue , Wang Bo 
Published: December 2024

AbstractHydroxyapatite (HA)-binding peptides are emerging as promising candidates for bone-targeted therapies due to their strong affinity for mineralized tissues and biocompatibility. However, most studies to date have focused onin vitrocharacterization, providing limited insight into theirin vivoperformance. This study bridges that gap by evaluating thein vivobehavior of HA-binding peptides D8, E8, YD8, and YE8 using fluorescence imaging to assess their biodistribution in healthy and pathological bone environments. In healthy animal models, D8 demonstrated the strongest binding across mineralized tissues, including the skull, femur, and tibia, while YD8 showed moderate binding. In contrast, E8 and YE8 exhibited limited localization influenced by peptide dosage and binding kinetics. Pathological models, including defective tibia and osteogenesis imperfecta (OIM) mice, revealed preferential accumulation of D8 and YD8 in structurally compromised regions, underscoring their potential for targeting diseased bone microenvironments. Fluorescence imaging, enhanced by spectral unmixing algorithms, proved effective for assessing peptide localization and distribution. These findings highlight the utility of HA-binding peptides for bone-targeted therapies and emphasize the importance ofin vivostudies in advancing their therapeutic and diagnostic applications. This work provides a foundation for optimizing peptide designs to improve specificity and efficacy in bone repair and regeneration.
Dopaminergic responses to identity prediction errors depend differently on the orbitofrontal cortex and hippocampus
Authors: Takahashi Yuji K. , Zhang Zhewei , Kahnt Thorsten , Schoenbaum Geoffrey 
Published: December 2024

SummaryAdaptive behavior depends on the ability to predict specific events, particularly those related to rewards. Armed with such associative information, we can infer the current value of predicted rewards based on changing circumstances and desires. To support this ability, neural systems must represent both the value and identity of predicted rewards, and these representations must be updated when they change. Here we tested whether prediction error signaling of dopamine neurons depends on two areas known to represent the specifics of rewarding events, the HC and OFC. We monitored the spiking activity of dopamine neurons in rat VTA during changes in the number or flavor of expected rewards designed to induce errors in the prediction of reward value or reward identity, respectively. In control animals, dopamine neurons registered both error types, transiently increasing firing to additional drops of reward or changes in reward flavor. These canonical firing signatures of value and identity prediction errors were significantly disrupted in rats with ipsilateral neurotoxic lesions of either HC or OFC. Specifically, HC lesions caused a failure to register either type of prediction error, whereas OFC lesions caused persistent signaling of identity prediction errors and much more subtle effects on signaling of value errors. These results demonstrate that HC and OFC contribute distinct types of information to the computation of prediction errors signaled by dopaminergic neurons.
AmpliPiper: A versatile amplicon-seq analysis tool for multilocus DNA barcoding
Authors: Bertelli Astra , Steindl Sonja , Kirchner Sandra , Schwahofer Paula , Haring Elisabeth , Szucsich Nikolaus , Kruckenhauser Luise , Kapun Martin 
Published: December 2024

AbstractThe advent of third generation sequencing technology has revolutionized parallelized sequencing of DNA fragments of varying lengths, such as PCR amplicons, which provides unprecedented new opportunities for large-scale and diverse DNA barcoding projects that, for example, aim to quantify the accelerating biodiversity crisis. However, the broad-scale application of these new technologies for biodiversity research is often hindered by the demand for advanced bioinformatics skills to carry out quantitative analyses. To facilitate the application of multilocus amplicon sequencing (amplicon-seq) data for biodiversity and integrative taxonomic research questions, we present AmpliPiper, an automated and user-friendly software pipeline which carries out bioinformatics analyses of multilocus amplicon-seq data generated with Oxford Nanopore (ONT) sequencing. AmpliPiper combines analysis methods for DNA barcoding data that include demultiplexing of pooled amplicon-seq data, haplotype-specific consensus sequence reconstruction, species identification based on comparison to the BOLD and GenBank databases, phylogenetic analyses and species delimitation. We demonstrate the applicability and workflow of our approach based on a newly generated dataset of 14 hoverfly (Syrphidae) samples that were amplified and sequenced at four marker genes. We further benchmark our approach with Sanger sequencing and simulated amplicon-seq data which show that DNA barcoding with ONT is both accurate and sensitive to detect even subtle genetic variation.
AI-first structural identification of pathogenic protein targets
Authors: Saluri Mihkel , Landreh Michael , Bryant Patrick 
Published: December 2024

AbstractThe likelihood for pandemics is increasing as the world population grows and becomes more interconnected. Obtaining structural knowledge of protein-protein interactions between a pathogen and its host can inform pathogenic mechanisms and treatment or vaccine design. Currently, there are 52 nonredundant human-pathogen interactions with known structure in the PDB, although there are 21’064 with experimental support in the HPIDB, meaning that only 0.2% of known interactions have known structure. Recent improvements in structure prediction of protein complexes based on AlphaFold have made it possible to model heterodimeric complexes with very high accuracy. However, it is not known how this translates to host-pathogen interactions which share a different evolutionary relationship. Here, we analyse the structural protein-protein interaction network between ten different pathogens and their human host. We predict the structure of 9452 human-pathogen interactions of which only 10 have known structure. We find that we can model 30 interactions with an expected TM-score of ≥0.9, expanding the structural knowledge in these networks three-fold. We select the highly-scoringFrancisella tularensisdihydroprolyl dehydrogenase (IPD) complex with human immunoglobulinKappaconstant (IGKC) for detailed analysis with homology modeling and native mass spectrometry. Our results confirm the predicted 1:2:1 heterotetrameric complex with potential implications for bacterial immune response evasion. We are entering a new era where structure prediction can be used to guide vaccine and drug development towards new pathogenic targets in very short time frames.
Persistent genomic erosion in whooping cranes despite demographic recovery
Authors: Fontsere Claudia , Speak Samuel A. , Caven Andrew J. , Rodríguez Juan Antonio , Wang Xuejing , Pacheco Carolina , Cassatt-Johnstone Molly , Femerling Georgette , Maloney Brigid , Balacco Jennifer , Collins Joanna , Sims Ying , Abueg Linelle , Fedrigo Olivier , Jarvis Erich D. , Hartup Barry K. , Shapiro Beth , Gilbert M. Thomas P. , van Oosterhout Cock , Morales Hernán E. 
Published: December 2024

AbstractIntegratingin-situ(wild) andex-situ(captive) conservation efforts can mitigate genetic diversity loss and help prevent extinction of endangered wild populations. The whooping crane (Grus americana) experienced severe population declines in the 18th century, culminating into a collapse to 16 individuals in 1941. Legal protections and conservation actions have since increased the population to approximately 840 individuals, yet the impact on genomic diversity remains unclear. We analysed the temporal dynamics of genomic erosion by sequencing a high-quality genome reference, and re-sequencing 16 historical and 37 modern genomes, including wild individuals and four generations of captive-bred individuals. Genomic demographic reconstructions reveal a steady decline, accelerating over the past 300 years with the European settlement of North America. Temporal genomic analyses show that despite demographic recovery, the species has lost 70% of its genetic diversity and has increased their inbreeding. Although the modern population bottleneck reduced the ancestral genetic load, modern populations possess more realized load than masked load, possibly resulting in a chronic loss of fitness. Integrating pedigree and genomic data, we underscore the role of breeding management in reducing recent inbreeding. Yet ongoing heterozygosity loss, load accumulation, and background inbreeding argues against the species’ downlisting from their current Endangered status on the IUCN Red List and the Endangered Species Act. The presence of private genetic variation in wild and captive populations suggests that wild-captive crosses could enhance genetic diversity and reduce the realized load. Our findings emphasize the role of genomics in informing conservation management and policy.
The Blueprint for Survival: The Blue Dasher Dragonfly as a Model for Urban Adaptation
Authors: Tolman Ethan R. , Gamett Ellie , Beatty Christopher D. , Goodman Aaron , Hahn Brittney , Benischek Christian , Castillo Gracie , Derderian Ethan , Fernandez-Juarez Santiago , Gallafent Ben , Jenson James , Jordan Dick , Schneider Magnolia , Salazar Roberto , Tamano Towako , Wei Maleah , Idec Jacob , Guralnick Rob , Ware Jessica L. , Kohli Manpreet K. 
Published: December 2024

AbstractHuman alteration of natural environments and habitats is a major driver of species decline. However, a handful of species thrive in human altered environments. The biology, distribution, population structure and molecular adaptations enabling certain species to thrive in human-altered habitats are not well understood. Here, we evaluate the population and functional genomics, niche space and geometric morphometrics of the blue dasher (Pachidiplax longipennis), one of the most ubiquitously observed insects in human altered habitats. We identify a number of genes involved with the success of the blue dasher in human altered habitats. We specifically identify genes contributing to immune function and response to oxidative stress that could be key to the success ofP. longipennisin degraded habitats.Intriguingly, some genes related to these functions are found in regions of high genomic conservation between populations ofP. longipennis, while others are in regions of the genome that are highly structured. Using one of the most robust locality datasets for any species to date, we also generate habitat suitability predictions which show thatP. longipennishas spread with urbanization, as humans have created more suitable habitat for this species. Our work demonstrates thatP. longipenniscould serve as a useful indicator for identifying modified habitats where generalists are pushing out regional specialists. Furthermore, the genes we have putatively identified as associated with the success ofP. longipennisin urban habitats are an important starting point for predicting which species will fare well in the Anthropocene.
Longitudinal Measurement Properties of the Participation Questionnaire for Preschoolers: Reliability, Responsiveness, and Interpretability
Authors: Nakamura Takuto , Koshio Iku , Maruyama Sho , Ikeda Kohei , Nagayama Hirofumi , Sasada Satoshi 
Published: December 2024

AbstractPurposeThis study aimed to evaluate the test−retest reliability, responsiveness, and interpretability of the Preschool Questionnaire for Participation (PQP), a tool for assessing participation in preschool children with autism spectrum disorder (ASD).MethodsA cohort study was conducted with data collected at four time points over six months from children with ASD aged 51–75 months. Test−retest reliability was examined using intraclass correlation coefficients (ICCs) for 275 participants who completed the study. Responsiveness was examined by analyzing correlations between changes in PQP scores and changes in multiple scales based on four predefined hypotheses. To assess interpretability, the Global Rating of Change (GRC) Scale was used as an anchor to analyze receiver operating characteristic curves and estimate the minimal important change (MIC).ResultsICCs ranged from 0.80 to 0.92 for individual factors and reached 0.93 for the total score. Three of the four hypotheses for responsiveness were supported within the expected range. However, the correlation between the GRC Scale and changes in PQP scores was below 0.3, preventing MIC calculation.ConclusionWhile the MIC could not be calculated, the PQP demonstrated test−retest reliability equivalent to or better than existing participation measures. Given the limited verification of responsiveness for other tools, the PQP’s strong longitudinal reliability and validity provide a foundation for future research.
An integrative analysis of consortium-based multi-omics QTL and genome-wide association study data uncovers new biomarkers for lung cancer
Authors: Wang Yanru , Wang Aoxuan , Xie Ning , Xu Xiaowen , Wang Xiang , Zhao Mengshen , Wang Xuan , Zhou Jiacheng , Zhao Yang , Hu Zhibin , Shen Hongbing , Hung Rayjean J. , Amos Christopher I. , Li Yi , Christiani David C. , Chen Feng , Wei Yongyue , Zhang Ruyang 
Published: December 2024

AbstractThe role of molecular traits (e.g., gene expression and protein abundance) in the occurrence, development, and prognosis of lung cancer has been extensively studied. However, biomarkers in other molecular layers and connections among various molecular traits that influence lung cancer risk remain largely underexplored. We conducted the first comprehensive assessment of the associations between molecular biomarkers (i.e., DNA methylation, gene expression, protein and metabolite) and lung cancer risk through epigenome-wide association study (EWAS), transcriptome-wide association study (TWAS), proteome-wide association study (PWAS) and metabolome-wide association study (MWAS), and then we synthesized all omics layers to reveal potential regulatory mechanisms across layers. Our analysis identified 61 CpG sites, 62 genes, 6 proteins, and 5 metabolites, yielding 123 novel biomarkers. These biomarkers highlighted 90 relevant genes for lung cancer, 83 among them were first established in our study. Multi-omics integrative analysis revealed 12 of these genes overlapped across omics layers, suggesting cross-omics interactions. Moreover, we identified 106 potential cross-layer regulatory pathways, indicating that cell proliferation, differentiation, immunity, and protein-catalyzed metabolite reaction interact to influence lung cancer risk. Further subgroup analyses revealed that biomarker distributions differ across patient subgroups. To share all signals in different omics layers with community, we released a free online platform, LungCancer-xWAS, which can be accessed athttp://bigdata.njmu.edu.cn/LungCancer-xWAS/. Our findings underscore the importance of xWAS which integrating various types of molecular quantitative trait loci (xQTL) data with genome-wide association study (GWAS) data to deepen understanding of lung cancer pathophysiology, which may provide valuable insights into potential therapeutic targets for the disease.
Fast FEM-based Electric Field Calculations for Transcranial Magnetic Stimulation
Authors: Cao Fang , Madsen Kristoffer Hougaard , Worbs Torge , Puonti Oula , Siebner Hartwig Roman , Schmitgen Arno , Kunz Patrik , Thielscher Axel 
Published: December 2024

AbstractObjectiveTo provide a Finite-Element Method (FEM) for rapid, repeated evaluations of the electric field induced by transcranial magnetic stimulation (TMS) in the brain for changing coil positions.ApproachPreviously, we introduced a first-order tetrahedral FEM enhanced by super- convergent patch recovery (SPR), striking a good balance between computational efficiency and accuracy (Saturninoet al2019J. Neural Eng.16066032). In this study, we refined the method to accommodate repeated simulations with varying TMS coil position. Starting from a fast direct solver, streamlining the pre- and SPR-based post-calculation steps using weight matrices computed during initialization strongly improved the computational efficiency. Additional speedups were achieved through efficient multi-core and GPU acceleration, alongside the optimization of the volume conductor model of the head for TMS.Main ResultsFor an anatomically detailed head model with ∼4.4 million tetrahedra, the optimized implementation achieves update rates above 1 Hz for electric field calculations in bilateral gray matter, resulting in a 60-fold speedup over the previous method with identical accuracy. An optimized model without neck and with adaptive spatial resolution scaled in dependence to the distance to brain grey matter, resulting in ∼1.9 million tetrahedra, increased update rates up to 10 Hz, with ∼3% numerical error and ∼4% deviation from the standard model. Region-of-interest (ROI) optimized models focused on the left motor, premotor and dorsolateral prefrontal cortices reached update rates over 20 Hz, maintaining a difference of <4% from standard results. Our approach allows efficient switching between coil types and ROI during runtime which greatly enhances the flexibility.SignificanceThe optimized FEM enhances speed, accuracy and flexibility and benefits various applications. This includes the planning and optimization of coil positions, pre-calculation and training procedures for real-time electric field simulations based on surrogate models as well as targeting and dose control during neuronavigated TMS.
Functional traits of ectomycorrhizal trees influence their effects on surrounding soil organic matter properties
Authors: Edwards Joseph D. , Dalling James W. , Fraterrigo Jennifer M. , Eddy William C. , Yang Wendy H 
Published: December 2024

AbstractEctomycorrhizal (EM) effects on forest ecosystem carbon (C) and nitrogen (N) cycling are highly variable, which may be due to underappreciated functional differences among EM-associating trees. We hypothesize that differences in functional traits among EM tree genera will correspond to differences in soil organic matter (SOM) dynamics.We explored how differences among three genera of angiosperm EM trees (Quercus, Carya,andTilia) in functional traits associated with leaf litter quality, resource use and allocation patterns, and microbiome assembly related to overall soil biogeochemical properties.In support of our hypothesis, we found consistent differences among EM tree genera in function traits.Quercustrees had lower litter quality, lower δ13C in SOM, higher δ15N in leaf tissues, greater oxidative extracellular enzyme activities, and higher EM fungal diversity thanTiliatrees, whileCaryatrees were often intermediary. These functional traits corresponded to overall SOM C and N dynamics and soil fungal and bacterial community composition.Our findings suggest that trait variation among EM-associating tree species should be an important consideration in assessing plant-soil relationships such that EM trees cannot be categorized as a unified functional guild.
RasGRP1 Signalling Programs Developing γδ-Thymocytes towards the γδT17 Lineage Through Control of c-Maf Expression
Authors: Joannou K. , Golec D.P. , Henao-Caviedes L.M. , May J.F. , Kelly R.G. , Baldwin T.A. 
Published: December 2024

AbstractThe γδ TCR instructively directs both lineage specification and effector programming of developing γδ T cells. However, the manner in which different TCR signal strengths and other auxiliary signals coordinate downstream of the γδ TCR to regulate γδ T cell development remains unclear. In this study we characterized the role of Ras guanyl-releasing protein 1 (RasGRP1) in the development and effector programming of γδ T cells. While RasGRP1 was not necessary for bulk γδ T cell generation, we found it required for efficient generation of Vγ4+thymocytes, and lineage-committed CD73+γδ T cells in the thymus and periphery. Despite a decrease in immature CD73+γδ thymocytes, we report an expansion of the perinatal wave of CD8+IFNγ+γδ T cell population in the absence of RasGRP1. IL-17 producing γδ T cells were significantly reduced in RasGRP1 KO mice, with a specific loss of Vγ2+γδ T cells that corresponds to a loss of c-Maf expression as early as the DN1d thymocyte stage. Critically, these adult-programmed γδT17s could express c-Maf in response to CCR9 stimulation, with RasGRP1 being required for CCR9-induced c-Maf expression. Thus, RasGRP1 activation serves as an important signalling hub in the effector programming of γδ T cells, which integrates signals from both non-TCR and TCR inputs to direct differentiation.
A novel isoform of Tensin1 promotes actin filament assembly for efficient erythroblast enucleation
Authors: Ghosh Arit , Coffin Megan , Diaz Dimitri M. , Barndt Sarah , Schulz Vincent , Gallagher Patrick , Lo Su Hao , Fowler Velia M. 
Published: December 2024

AbstractMammalian red blood cells are generated via a terminal erythroid differentiation pathway culminating in cell polarization and enucleation. Actin filament polymerization is critical for enucleation, but the molecular regulatory mechanisms remain poorly understood. We utilized publicly available RNA-seq and proteomics datasets to mine for actin-binding proteins and actin- nucleation factors differentially expressed during human erythroid differentiation and discovered that a focal adhesion protein—Tensin-1—dramatically increases in expression late in differentiation. Remarkably, we found that differentiating human CD34+ cells express a novel truncated form of Tensin-1 (eTNS1; Mr ∼125 kDa) missing the N-terminal half of the protein, due to an internal mRNA translation start site resulting in a unique exon 1. eTNS1 localized to the cytoplasm during terminal erythroid differentiation, with no apparent membrane association or focal adhesion formation. Knocking out eTNS1 had no effect on assembly of the spectrin membrane skeleton but led to impaired enucleation and absent or mis-localized actin filament foci in enucleating erythroblasts. We conclude that eTNS1 is a novel regulator of actin filament assembly during human erythroid terminal differentiation required for efficient enucleation.
Macroevolutionary changes in gene expression response to an immune stimulus across the diversity of fishes
Authors: Flanagan Ben A. , Fuess Lauren E. , Vrtílek Milan , Roth-Monzón Andrea , Bolnick Daniel I. 
Published: December 2024

AbstractOur understanding of the vertebrate immune system is dominated by a few model organisms such as mice. This use of a few model systems is reasonable if major features of the immune systems evolve slowly and are conserved across most vertebrates, but may be problematic if there is substantial macroevolutionary change in immune responses. Here, we present a test of the macroevolutionary stability, across 15 species of jawed fishes, of the transcriptomic response to a standardized immune challenge. Intraperitoneal injection of an immune adjuvant (alum) induces a fibrosis response in nearly all jawed fishes, which in some species contributes to anti-helminth resistance. Despite this conserved phenotypic response, the underlying transcriptomic response is highly inconsistent across species. Although many gene orthogroups exhibit differential expression between saline versus alum-injected fish in at least one species, few orthogroups exhibit consistent differential expression across species. This result suggests that although the phenotypic response to alum (fibrosis) is highly conserved, the underlying gene regulatory architecture is very flexible and cannot readily be extrapolated from any one species to fishes (or vertebrates) more broadly. The vertebrate immune response is remarkably changeable over macroevolutionary time, requiring a diversity of model organisms to describe effectively.