bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban effects on timing and variability of diel activity differ across passerine species and seasons
Authors: Capilla-Lasheras Pablo , Branston Claire J. , Baker Paul , Cochrane Cara , Helm Barbara , Dominoni Davide M. 
Published: January 2025

Abstract1. Life on Earth is adapted to rhythmic cycles in environmental conditions throughout the day and year via diel patterns of behavioural activity.2. Urban conditions can disrupt such behavioural rhythms of activity. However, most studies so far have investigated urban effects on patterns of activity of single species in a single season. Additionally, we know little about the level of between and within-individual variation in urban and non-urban populations, and whether they differ.3. Here, we use automated radio telemetry to record patterns of daily activity in six passerine species (blackbird, robin, great tit, blue tit, dunnock and chaffinch) across two urban and two forest populations during the pre-breeding and post-breeding season. We investigate urban effects on five activity-related traits: time of activity onset, time of activity end, duration of diurnal activity, level of diurnal activity and level of nocturnal activity. We employ statistical tools that allow us to estimate urban effects on mean phenotypic values, but also quantify urbanversusforest differences in between-individual and within-individual phenotypic variation.4. We found the strongest urban effects on time of activity onset in blackbirds and robins during the pre-breeding season: urban populations of blackbird and robin started their daily activity earlier than their forest counterparts. We did not find this effect in the other species. Urban populations of all species showed higher levels of nocturnal activity than forest populations, but this effect was not offset by lower diurnal activity, suggesting that urban birds may incur higher daily energetic demands.5. Lastly, our analysis revealed large and consistent differences in variation in the investigated timing traits. Urban birds were more variable between individuals, implying lower population synchronization, and more variable within individuals, implying less consistent behaviour than their forest counterparts. Conversely, activity levels were more variable in forest birds.6. We conclude that, for birds, urban life is associated with less rest, less consistency, and lower synchronicity, but that effect sizes depend on species and time of the year. Our results warn against generalising the effects of urbanisation on daily rhythms of birds, and call for future studies to understand the mechanisms behind species and seasonal differences.
TrimNN: Characterizing cellular community motifs for studying multicellular topological organization in complex tissues
Authors: Yu Yang , Wang Shuang , Li Jinpu , Yu Meichen , McCrocklin Kyle , Kang Jing-Qiong , Ma Anjun , Ma Qin , Xu Dong , Wang Juexin 
Published: January 2025

ABSTRACTThe spatial organization of cells plays a pivotal role in shaping tissue functions and phenotypes in various biological systems and diseased microenvironments. However, the topological principles governing interactions among cell types within spatial patterns remain poorly understood. Here, we present theTriangulation Cellular CommunityMotifNeuralNetwork (TrimNN), a graph-based deep learning framework designed to identify conserved spatial cell organization patterns, termed Cellular Community (CC) motifs, from spatial transcriptomics and proteomics data. TrimNN employs a semi-divide-and-conquer approach to efficiently detect over-represented topological motifs of varying sizes in a triangulated space. By uncovering CC motifs, TrimNN reveals key associations between spatially distributed cell-type patterns and diverse phenotypes. These insights provide a foundation for understanding biological and disease mechanisms and offer potential biomarkers for diagnosis and therapeutic interventions.
Gene regulatory networks and essential transcription factors for de novo originated genes
Authors: Peng Junhui , Wang Bing-Jun , Svetec Nicolas , Zhao Li 
Published: January 2025

AbstractThe regulation of gene expression is crucial for the functional integration of evolutionarily young genes, particularly those that emerge de novo. However, the regulatory programs governing the expression of de novo genes remain unknown. To address this, we applied computational methods to single-cell RNA sequencing data, identifying key transcription factors likely instrumental in regulating de novo genes. We found that transcription factors do not have the same propensity for regulating de novo genes; some transcription factors contain more de novo genes than others in their regulon. Leveraging genetic and genomic tools inDrosophila, we further examined the role of two key transcription factors and the regulatory architecture of novel genes. Our findings identify key transcription factors associated with the expression of de novo genes and provide new insights into how modifications in existing transcription factors enable the emergence, maintenance, and regulation of de novo genes.
Polyglutamine expansion induced dynamic misfolding of Androgen Receptor
Authors: Heling Laurens W.H.J. , Sheikhhassani Vahid , Ng Julian , van Vliet Morris , Jiménez-Panizo Alba , Alegre-Martí Andrea , Woodard Jaie , van Roon-Mom Willeke , McEwan Iain J , Estébanez-Perpiñá Eva , Mashaghi Alireza 
Published: January 2025

AbstractSpinal bulbar muscular atrophy (SBMA) is caused by a polyglutamine expansion (pQe) in the N-terminal transactivation domain of human androgen receptor (AR-NTD), resulting in a combination of toxic gain- and loss-of-function mechanisms. The structural basis of these processes has not been resolved due to the disordered nature of the NTD, which hinders experimental analyses of its detailed conformations. Here, using extensive computational modelling, we show that AR-NTD forms dynamic compact regions, which upon pQe re-organize dynamically, mediated partly by direct pQ interaction with the Androgen N-Terminal Signature (ANTS) motif. The altered dynamics of the NTD result in a perturbation of interdomain interactions, with potential implications for binding of the receptor protein to its response element. Oligomeric aggregation of the dynamic misfolded NTD exposes pQe, but blocks tau-5 and the FQNLF motif, which could lead to aberrant receptor transcriptional activity. These observations suggest a structural mechanism for AR dysfunction in SBMA.
T505A variant of ETV5 promotes proliferation of precursor B cells in a mouse model of acute lymphoblastic leukemia
Authors: Yi Joshua , Wu Michael , Dowling Michaela L. , MacKenzie Allanna C. E. , Iansavitchous James , DeKoter Rodney P. 
Published: January 2025

AbstractPrecursor B cell acute lymphoblastic leukemia (pre-B-ALL) arises as a result of precursor B cells acquiring driver mutations that lead to arrested differentiation and increased proliferation. Identification of driver mutations and understanding their biological function is critical to understanding pre-B-ALL development and advancing disease treatment. Using a mouse model of pre-B-ALL driven by deletion of genes encoding the related E26-transformation-specific (ETS) transcription factors PU.1 and Spi-B, we performed whole exome sequencing to identify secondary driver mutations. We identified recurrent variants in E26 transformation-specific transcription variant 5 (ETV5) resulting in R392P, V444I, and T505A amino acid changes. We found that the R392P and V444I variants altered the ability of ETV5 to bind to DNA using electrophoretic mobility shift assay. R392P and V444I variants did not activate a Dual-Specificity-Phosphatase 6 (DUSP6) reporter. In contrast, T505A ETV5 could interact with DNA and activate the DUSP6 promoter. To determine biological function, we forced expression of wild type, R392P, V444I, or T505A ETV5 in an interleukin-7-dependent pre-B cell line. Proliferation and apoptosis assays showed that T505A ETV5 conferred a proliferative advantage to pre-B cells. RNA sequencing showed that expression of ETV5 variants significantly altered gene expression in cultured cells. Through gene set enrichment analysis, T505A was suggested to downregulate the p53 pathway and the anti-proliferative protein, B cell translocation gene 2 (encoded byBtg2). In summary, these data suggest that ETV5 mutations play a role in pre-B-ALL by affecting proliferation and cell survival.
The relationship between auditory brainstem responses, cognitive ability, and speech-in-noise perception among young adults with normal hearing thresholds
Authors: DiNino Mishaela , Crowell Jenna , Kloiber Ilsa , Polonenko Melissa J. 
Published: January 2025

AbstractPurposeThe goal of this research was to determine the contributions of auditory neural processing and cognitive abilities to predict performance on a competing talker task in young, normal hearing adults.MethodsTwo experiments were performed, each with separate cohorts of ∼30 young adults with normal hearing who performed a competing talker task which included a high-pass filtered condition that was designed to be more sensitive to auditory nerve functioning than are commonly used speech-in-noise perception tests. Predictors of performance on this speech-in-speech task included ABR waves I and V metrics and cognitive task performance. Experiment one included click ABRs at a moderate level commensurate with the level of the competing talker task, as well as the cognitive digit span working memory task. Experiment two included high-intensity click clinical ABRs and three cognitive tasks from the NIH Toolbox V3 that assessed working memory, cognitive flexibility and attention, and inhibitory control: List Sorting Working Memory, Dimensional Change Card Sort, and Flanker Inhibitory Control and Attention tests, respectively.ResultsPerformance on the high-pass competing talker task varied across participants in both experiments. This variability was predicted by performance on the inhibitory control task, but not the tasks involving working memory or cognitive flexibility, nor by any of the auditory processing metrics from moderate or high-intensity click ABRs.ConclusionsAmong two groups of young adults with normal hearing, cognitive factors with very similar demands to the competing talker task seem to play the greatest role in speech-in-noise perception.
Dietary iron deficiency in the adult mouse increases brain endothelial uptake and blood-brain barrier transport of a high-affinity, anti-transferrin receptor antibody
Authors: Kostrikov Serhii , Johnsen Kasper Bendix , Burkhart Annette , Andresen Thomas Lars , Moos Torben 
Published: January 2025

AbstractBackground and objectivesBrain capillary endothelial cells (BCECs) express transferrin receptor 1 (TfR1) to ensure sufficient iron transport into the brain across the blood-brain barrier (BBB). Our main objective was to examine adult mice subjected to dietary iron deficiency (ID) for possible changes in the content of TfR1 in BCECs and the influence thereof on the uptake and transport of high-affinity anti-transferrin receptor IgG1 antibodies (clone Ri7217).Material and methodsWe subjected adult, female mice to dietary ID for 8 weeks. Iron and copper were measured using inductively coupled plasma mass spectrometry (ICP-MS) in various tissues, including total brain and isolated brain capillaries. Possible effects of ID on cerebral angioarchitecture were estimated using 3D confocal microscopy of optically cleared brain samples with endothelium labelled using intravenous injection of wheat germ agglutinin with subsequent machine learning-based segmentation and vascular tracing. TfR1 was quantified using ELISA. Ri7217 antibodies were conjugated with 1 nm nanogold and brain uptake quantified using ICP-MS.ResultsID significantly reduced the iron content in isolated brain capillaries, liver, spleen, kidney, heart and skeletal muscles. ID increased the copper content in the brain. Analysis of cerebral cortex angioarchitecture revealed no changes following dietary ID except for a minor increase in tortuosity of small-caliber vessels. TfR1 protein was unchanged in the total brain and isolated brain capillaries. In contrast, uptake of nanogold-conjugated Ri7217 increased in the total brain, the supernatant fraction of isolated brain capillaries representing the post-vascular compartment, liver, spleen, and dissected retinae.ConclusionsTargeting TfR1 in ID revealed increased uptake and transport across the BBB of Ri7217 antibodies. Possibly the elevated transport of transferrin receptors through BCECs is due to the increased trafficking of transferrin receptor-containing vesicles in ID, which appeared to have no major effects on the brain angioarchitecture.
Balancing Stability and Recovery: Impact of Spinal Fusion Length on Surgical Site Infections and Functional Outcomes in Traumatic Thoracic and Thoracolumbar Spinal Cord Injuries
Authors: Leister Iris , Katzensteiner Moritz , Wutte Christof , Mach Orpheus , Maier Doris , Vogel Matthias 
Published: January 2025

AbstractBackgroundSpinal surgeries after traumatic thoracic or thoracolumbar spinal cord injuries (SCI) often involve extensive instrumentation, leading to an increased risk of surgical site infections (SSIs) and complications. This study investigates whether the number of spinal levels fused impacts functional recovery and the frequency of SSIs in individuals with vertebral fractures in the thoracic and/or lumbar spine and SCI.MethodsIn this retrospective analysis of 282 patients with traumatic thoracic or thoracolumbar SCI, data across two periods (2005–2009 vs. 2018–2022) were compared, including variables such as demographics, setting of the initial surgery (specialized SCI center or general trauma center), SCI severity, number of levels fused, fracture classification, the need for revision surgery, the presence of polytrauma and/or traumatic brain injury (TBI), and the occurrence of SSIs during hospitalization. Functional independence was assessed using the Spinal Cord Independence Measure (SCIM III). Unbiased recursive partitioning (URP-CTREE) was used to identify predictors of SSIs and functional outcomes.ResultsPatients undergoing longer fusions had a significantly higher rate of SSIs (median fusion length: 5 vs. 3 levels, p = 0.02). Revision surgery and age over 57 were identified as key predictors of SSIs. Shorter fusions (two spinal segments or less) were associated with better functional recovery, particularly in more severe SCI (AIS A, B, or C).ConclusionLonger fusion lengths increase the risk of SSIs and are linked to poorer functional outcomes in patients with thoracic and thoracolumbar SCI. Minimizing fusion length might optimize surgical outcomes and reduce complications. Future research should refine surgical strategies to balance stability with functional recovery.
Umbilical cord blood pTau217 and BD-tau are associated with markers of neonatal hypoxia: a prospective cohort study
Authors: Payne Emma , Gonzalez-Ortiz Fernando , Kramer Kaitlin , Payne Thomas , Marathe Shreeya , Mahajan Neha , Liu Ashly , Barry Jessica , Duckworth Andrew , Brookes Mitchell , de Vries Bradley , Moran Benjamin , Manning Helen , Blennow Kaj , Zetterberg Henrik , Zalcberg David , Sanders Robert D. 
Published: January 2025

AbstractObjectiveCurrent methods for early detection of hypoxic–ischemic encephalopathy (HIE) are limited by lack of specificity, cost, and time constraints. Blood tau protein concentrations reflect neuropathology in adults. This study examines tau as a potential HIE biomarker in neonates by relating cord blood levels to short-term fetomaternal outcomes.DesignProspective cohort study.SettingRoyal Prince Alfred Hospital—a large Australian tertiary referral centre. Population: 107 maternal participants.MethodsSimoa analysis of umbilical cord blood pTau217 and brain-derived (BD)-tau.Main Outcome MeasuresPrimary: association of BD-tau with non-reassuring fetal status. Secondary: 1) correlations between cord blood tau and other biomarkers; 2) associations between tau levels and risk factors for fetomaternal morbidity; 3) associations between tau levels and short-term fetomaternal outcome.ResultsOf 509 deliveries, cord blood was analysed in 107/110 recruited maternal participants. BD-tau correlated with non-reassuring fetal status (OR=3.0;95%CI=1.6– 5.7;p=0.001), though not when adjusting for mode of delivery and gestational age. BD-tau was higher in vaginal deliveries, and positively associated with pTau217, NfL, and lactate (p<0.001), and negatively associated with pH and base excess. pTau217 was higher in preterm neonates and was associated with neurofilament light chain (Spearman’s rho=0.44,p<0.001). BD-tau and pTau217 were associated with maternal hypertension and placental abnormalities.ConclusionsCord blood BD-tau correlates with markers of fetal hypoxia, whilst pTau217 levels may indicate broader neurodevelopmental vulnerability. Further studies could explore whether these findings translate to clinical use of tau as an HIE biomarker.FundingUS National Institutes of Health (grant:R01AG063849-01).
Type-2 diabetes biomarker discovery and risk assessment through saliva DNA methylome
Authors: Guo Wenbin , Morselli Marco , Paul Kimberly C. , Thompson Michael , Ritz Beate , Pellegrini Matteo 
Published: January 2025

AbstractThe rising prevalence of type 2 diabetes (T2D) motivates innovative strategies to deepen disease understanding and enhance diagnostic capabilities. This study measures diabetes-specific epigenetic signals in saliva, establishing saliva DNA methylome as a promising medium for T2D screening and study. By integrating comprehensive whole-genome bisulfite sequencing (WGBS) and high-depth targeted bisulfite sequencing (TBS), we developed a cost-efficient two-step approach to profiling DNA methylation at regions of interest. WGBS analysis confirmed T2D-specific methylation signatures in saliva, revealing their enrichment in immune and metabolic regulation pathways. TBS enabled accurate cell type deconvolution, revealing minimal differences in cellular composition between diabetic and non-diabetic samples, suggesting intrinsic molecular changes drive the observed methylation changes. Epigenome-wide association studies further identified significant CpG sites, notably in theABCG1region, with strong potential for T2D status prediction. These findings validate the saliva DNA methylome as a scalable, non-invasive resource for T2D biomarker discovery, advancing opportunities in T2D screening, risk assessment, and personalized medicine.
Whole-genome evaluation of genetic rescue: the case of a curiously isolated and endangered butterfly
Authors: MacDonald Zachary G. , Dupuis Julian R. , Glasier James R. N. , Sissons Robert , Moehrenschlager Axel , Bradley Shaffer H. , Sperling Felix A. H. 
Published: January 2025

AbstractGenetic rescue, or the translocation of individuals among populations to augment gene flow, can help ameliorate inbreeding depression and loss of adaptive potential in small and isolated populations. Genetic rescue is currently under consideration for an endangered butterfly in Canada, the half-moon hairstreak (Satyrium semiluna). A small, unique population persists in Waterton Lakes National Park, Alberta, isolated from other populations by >350km. However, whether genetic rescue would actually be helpful has not been evaluated. Here, we generate the first chromosome-level genome assembly and whole-genome resequence data for the species. We find that the Alberta population’s genetic diversity is extremely low and very divergent from the nearest populations in British Columbia and Montana. Runs of homozygosity suggest this is due to a long history of inbreeding, and coalescent analyses show that the population has been small and isolated, yet stable for up to 40k years. When a population maintains its viability despite inbreeding and low genetic diversity, it has likely undergone purging of deleterious recessive alleles and could be threatened by their reintroduction via genetic rescue. Ecological niche modelling indicates that the Alberta population also exhibits environmental associations that are atypical of the species. Together, these results suggest that population crosses are likely to result in outbreeding depression. We infer that, in this case, genetic rescue has a relatively unique potential to be harmful rather than helpful at present. However, due to reduced adaptive potential, the Alberta may still benefit from future genetic rescue as climate conditions change. Proactive experimental population crosses should be completed to assess reproductive compatibility and offspring fitness.
Cerebellar organoids model cell type-specificFOXP2expression during human cerebellar development
Authors: Apsley Elizabeth J. , Riepsaame Joey , Cowley Sally A. , Becker Esther B. E. 
Published: January 2025

AbstractIn this study, we demonstrate the potential of cerebellar organoids for studying features of early human cerebellar development. Forkhead box protein P2 (FOXP2) is a transcription factor associated with speech and language development that is highly expressed in the developing brain. However, little attention has been directed to the study of FOXP2 in the early developing cerebellum. We used CRISPR gene editing in human iPSCs to generate a fluorescent FOXP2-reporter line. By combining transcriptomic analysis of iPSC-derived cerebellar organoids with published cerebellar datasets, we describe the expression and identify potential downstream targets of FOXP2 in the early developing human cerebellum. Our results highlight expression ofFOXP2in early human Purkinje cells and cerebellar nuclei neurons, and the vulnerability of these cell populations to neurodevelopmental disorders. Our study demonstrates the power of cerebellar organoids to model early human developmental processes and disorders.
A deep-learning tool for species-agnostic integration of cancer cell states
Authors: Rub Jonathan , Chan Jason E , Sussman Carleigh , Tap William D. , Singer Samuel , Tammela Tuomas , Betel Doron 
Published: January 2025

AbstractGenetically engineered mouse models (GEMM) of cancer are a useful tool for exploring the development and biological composition of human tumors and, when combined with single-cell RNA-sequencing (scRNA-seq), provide a transcriptomic snapshot of cancer data to explore heterogeneity of cell states in an immunocompetent context. However, cross-species comparison often suffers from biological batch effect and inherent differences between mice and humans decreases the signal of biological insights that can be gleaned from these models. Here, we develop scVital, a computational tool that uses a variational autoencoder and discriminator to embed scRNA-seq data into a species-agnosticlatent spaceto overcome batch effect and identify cell states shared between species. We introduce the latent space similarity (LSS) score, a new metric designed to evaluate batch correction accuracy by leveraging pre-labeled clusters for scoring instead of the current method of creating new clusters. Using this new metric, we demonstrate scVital performs comparably well relative to other deep learning algorithms and rapidly integrates scRNA-seq data of normal tissues across species with high fidelity. When applying scVital to pancreatic ductal adenocarcinoma or lung adenocarcinoma data from GEMMs and primary patient samples, scVital accurately aligns biologically similar cell states. In undifferentiated pleomorphic sarcoma, a test case with noa prioriknowledge of cell state concordance between mouse and human, scVital identifies a previously unknown cell state that persists after chemotherapy and is shared by a GEMM and human patient-derived xenografts. These findings establish the utility of scVital in identifying conserved cell states across species to enhance the translational capabilities of mouse models.