bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphology of male genitalia and legs reveals the classification of Mesozoic Zoraptera (Insecta)
Authors: Kočárek Petr , Kočárková Ivona , Kundrata Robin 
Published: January 2025

AbstractZoraptera is a small insect order with less than 50 described species from mostly tropical and subtropical regions of the World. The current system of extant Zoraptera is based on the results of molecular phylogeny combined with the morphology of male genitalia, and supplemented by the characters on the male abdomen and a number of metatibial spurs. However, fossil representatives of Zoraptera have not yet been classified into the modern system and most of them remained in the collecting genusZorotypusSilvestri, 1913, because the genitalia were not observable or examined in detail. In this study, for the first time, we describe and critically evaluate the male genitalia and other principal diagnostic characters of all available Mesozoic Zoraptera. Our results lead to the first proposal of the generic classification of Mesozoic Zoraptera. We describe two new genera,Cretozorosgen. nov. andBurmazorosgen. nov., reinstatePaleospinosusKaddumi, 2005, stat. restit. from synonymy with the subgenusOctozorosEngel, 2003 (inZorotypus), and elevateOctozorosEngel, 2003 to a genus level.Cretozorosgen. nov.,Paleospinosusstat. restit. andOctozorosstat. nov. are classified in Spiralizoridae: Latinozorinae, whileBurmazorosgen. nov. andXenoburmiticusEngel & Grimaldi, 2002 are classified in Zorotypidae: Zorotypinae. Altogether, it was possible to classify nine out of the 11 currently recognized species of Mesozoic Zoraptera.Zorotypus hukawngiChen & Su 2019 is synonymized withCretozoros acanthothorax(Engel & Grimaldi, 2002), comb. nov. andZorotypus hirsutusMashimo, 2018 is synonymized withOctozoros robustus(Liu, Zhang, Cai & Li, 2018), stat. restit., comb. nov., which is simultaneously restituted from the synonymy withOctozoros cenomanianus(Yin, Cai & Huang, 2018), comb. nov. The classification of Mesozoic Zoraptera into the modern system enables us to better understand the diversity of their internal lineages during the early evolution of this enigmatic insect order.
Freshwater fish community assessment using eDNA metabarcoding vs. capture-based methods: differences in efficiency and resolution coupled to habitat and ecology
Authors: Curto Manuel , Batista Sofia , Santos Carlos D. , Ribeiro Filipe , Nogueira Sofia , Ribeiro Diogo , Prindle Benjamin , Licari Daniel , Riccioni Giulia , Dias Diogo , Pina-Martins Francisco , Jentoft Sissel , Veríssimo Ana , Alves Maria Judite , Gante Hugo F. 
Published: January 2025

AbstractEnvironmental DNA (eDNA) metabarcoding has revolutionized ecological and environmental research by describing communities without relying on direct observations, making it a powerful, non-invasive, and cost-effective tool in biodiversity monitoring. However, implementation of eDNA as a standard protocol in long-term monitoring programs, that have traditionally relied on capture-based methods, poses challenges in terms of data comparability. Here, we compared freshwater fish communities assessed through eDNA metabarcoding and electrofishing, across 35 sampling sites in the lower Tagus River basin, Portugal. For most species or species-groups analyzed individually (13 out of 17), there was a significant correspondence between electrofishing and eDNA metabarcoding detections. The correspondence was weaker when comparing the number of specimens captured by electrofishing with the number of eDNA metabarcoding reads, with seven out of 13 taxa showing significant relationships. Species richness estimates based on the two methods were very similar at the basin level. The methods yielded significantly different species compositions, although these differences were driven by samples collected in the Tagus main channel, which is wider and has higher flow rates than tributaries. Benthic and shoreline fish communities showed similar species composition in the two methods, but this was not the case for pelagic communities, probably due to the higher water turnover of the pelagic zone and electrofishing inefficiency. Our results highlight the high potential of eDNA metabarcoding as a complementary method to electrofishing for freshwater fish monitoring, though further validation is needed to assess biases related to site-specific hydrological conditions and the ecology of the target species.
Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters
Authors: da Silva Antunes Ricardo , Fajardo-Rosas Vicente , Yu Esther Dawen , Gálvez Rosa Isela , Abawi Adam , Alexandar Escarrega E. , Martínez-Pérez Amparo , Johansson Emil , Goodwin Benjamin , Frazier April , Dan Jennifer M. , Crotty Shane , Seumois Grégory , Weiskopf Daniela , Vijayanand Pandurangan , Sette Alessandro 
Published: January 2025

SUMMARYThe long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics in Spike-specific humoral and cellular immune responses across multiple vaccine doses. While antibody titers incrementally increased and stabilized with each booster, T cell responses rapidly plateaued, maintaining remarkable stability across CD4+ and CD8+ subsets. Notably, approximately 30% of participants showed CD4+ T cell reactivity to non-Spike antigens, consistent with asymptomatic infections. Single-cell RNA sequencing revealed a diverse landscape of Spike-specific T cell phenotypes, with no evidence of increased exhaustion or significant functional impairment. However, qualitative changes were observed in individuals with evidence of asymptomatic infection, exhibiting unique immunological characteristics, including increased frequencies of Th17-like CD4+ T cells and GZMKhi/IFNR CD8+ T cell subsets. Remarkably, repeated vaccinations in this group were associated with a progressive increase in regulatory T cells, potentially indicating a balanced immune response that may mitigate immunopathology. By regularly stimulating T cell memory, boosters contribute to a stable and enhanced immune response, which may provide better protection against symptomatic infections.
A dietary intervention following incretin analog treatment restores adipose tissue functions in diet-induced obese mice
Authors: Seuntjens Joke , De Gols Jente , Davies Bethan K , Van Looy Fien , Stockmans Ingrid , Moermans Karen , Carmeliet Geert , Matthys Christophe , Vangoitsenhoven Roman , Van der Schueren Bart , Stegen Steve , Shimobayashi Mitsugu 
Published: January 2025

ABSTRACTObesity affects more than 15% of the world population and is associated with the development of glucose intolerance and type 2 diabetes. In recent years, incretin analogs are prescribed at a high rate for treatment of obesity and diabetes due to their potent effects on lowering bodyweight and improving glucose homeostasis. However, recent studies suggest that many patients do not stay on incretin analog therapy and thereby rapidly regain bodyweight. The non-compliance of patients to incretin analog therapy is not only due to drug shortage but also insufficient knowledge on the long-term effects of the therapy. To address this knowledge gap and provide a long-term therapy strategy for obesity, we examined the effects of incretin analog treatment and withdrawal on adipose tissue functions in diet-induced obese mice. Our transcriptome data suggest that incretin analog treatment restored most of obesity-mediated deregulated gene expression in adipose tissue. However, genes encoding lipogenic enzymes, downregulated by diet-induced obesity, were not restored by incretin analog treatment. Upon therapy withdrawal, mice displayed rapid bodyweight regain, impaired adipose tissue function, and glucose intolerance. In contrast, a dietary intervention following incretin analog therapy withdrawal restored lipogenic gene expression in adipose tissue, maintained glucose homeostasis, increased lean mass and minimized body weight regain. Our findings revealed the effects of incretin analog therapy and therapy withdrawal on adipose tissue and highlight the importance of a dietary intervention following incretin analog therapy, which may contribute to the development of long-term therapy guidelines of incretin analog therapy for patients with obesity.
Molecular mechanisms of sexual dimorphism in cancer through improved miRNA regulation-level network-based approach: MIRROR2
Authors: Alfano Caterina , Filetti Marco , Farina Lorenzo , Petti Manuela 
Published: January 2025

AbstractA current open challenge in precision medicine is sex-specific medicine: the study of how sex-based biological differences influence people’s health. With recent advancements in high-throughput technologies, large-scale molecular data are being generated for individual cancer patients, however, extracting meaningful insights from these complex datasets remains a challenge. Network-based approaches, being inherently holistic, can lead to a better understanding of the molecular mechanisms underlying a disease. For this reason, this study focuses on the development of a network-based method to investigate sexual dimorphism in cancer using transcriptomic data. Previous studies have already shown how miRNAs are involved in differentiating patients by sex in different types of cancer; however, they focused only on evaluating changes in the expression level, without conducting a more comprehensive analysis of miRNA expression or investigating miRNAs’ targets. The aim of this study is therefore to carry out a multi-layer study involving both miRNAs and their target genes’ expression data. In particular, we developed a generalizable algorithm (MIRROR2), which can be used on cancer patients to help identify key regulatory mechanisms and molecules that act as differentiators between males and females. Here we implemented and tested MIRROR2 on three different cancers (colon adenocarcinoma, hepatocellular carcinoma, and low-grade gliomas) and assessed its performance by comparing it to state-of-the-art approaches. This revealed MIRROR2’s efficacy in identifying sex-specific key genes (and how to integrate them with clinical features), presenting it as a viable alternative to state-of-the-art methods which fail to capture these differences.
High-precision cell-type mapping and annotation of single-cell spatial transcriptomics with STAMapper
Authors: Shen Qunlun , Dong Kangning , Zhang Shuqin , Zhang Shihua 
Published: January 2025

AbstractRecent advances in single-cell spatial transcriptomics (scST) have enabled the analysis of gene transcription levels in individual cells while preserving their spatial positions. Cell-type mapping and annotation are crucial in understanding the complex interactions between cells and their microenvironments within a spatial context. To this end, we develop a heterogeneous graph neural network, STAMapper, to transfer the cell-type labels from single-cell RNA-seq data to scST data. STAMapper captures both the expression similarity among cells and the expression relationships between cells and genes and adopts a graph attention classifier to conduct semi-supervised learning for more accurate cell-type prediction. We collected 81 scST datasets consisting of 344 slices and 16 paired scRNA-seq datasets from eight technologies and five tissues to validate the efficiency of STAMapper. STAMapper achieved the best performance on 75 out of 81 datasets compared to competing methods in accuracy. STAMapper demonstrated enhanced performance over manual annotations, particularly at the boundaries of cell clusters, enabled the unknown cell-type detection in scST data, and exhibited precise cell subtype annotations. Additionally, STAMapper provided biologically meaningful gene embeddings, facilitating the identification of shared or unique gene modules across datasets.
Phylogenomic synteny analysis tracks conserved ancient polyploid-derived triplicated genomic blocks across Asteraceae genomes
Authors: Feng Tao , McKibben Michael , Lovell John , Michelmore Richard , Rieseberg Loren H. , Barker Michael , Schranz Eric M. 
Published: January 2025

AbstractThe Asteraceae (Compositae) is the largest flowering plant family, ubiquitous in most terrestrial communities, and morphologically hyper-diverse. An ancient whole genome triplication (paleo-hexaploidization) occurred at approximately the same time as the evolutionary innovation and adaptive radiation of the family during the middle Eocene. Despite its importance, the genomic contents arising from this triplication have yet to be tracked in context of the Asteraceae genome evolution. We applied a synteny oriented phylogenomic analysis of 21 Asterales genomes and to study the paleo-hexaploidization and its consequences to gene, trait, and genome evolution. We identified 15 ancestral linkage groups (ALGs) that date back to the common diploid ancestor of all Asteraceae. Each of these groups was triplicated, resulting in 45 genomic blocks (3×15), which serve as the foundation for cross-family analyses. We demonstrate the complex evolutionary dynamics of the 45 genomic blocks across the Asteraceae phylogeny. We found that modern genomes are genetic mosaics of three progenitor genomes by extensive genomic exchange, chromosomal shuffling and gene fractionation. 157 genes retained three paleo-hexaploid derived syntenic paralogs across most Asteraceae species. Transcription factors (TFs) and auxin-related genes are significantly overrepresented in the conserved triplets, and expression of the paleo-hexaploidy paralogs is spatiotemporally differentiated. These genes are involved in the development of floral capitulum, a remarkable morphological innovation of the family. The discovery of conserved triplicated genes can direct further study to understand the evolutionary innovation, and the synteny-phylogenomic framework and ALGs provide a comparative framework to characterize newly sequenced Asteraceae genomes.
Impaired Myelination in Multiple Sclerosis Organoids: p21 Links Oligodendrocyte Dysfunction to Disease Subtype
Authors: Daviaud Nicolas , Mehta Tanmay , Holzman William , McDermott Annie , Sadiq Saud A 
Published: January 2025

ABSTRACTMultiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are strongly implicated in its pathogenesis. We derived cerebral and spinal cord organoids from induced pluripotent stem cells (iPSC) from healthy controls as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients to investigate and compare oligodendrocyte differentiation and myelination capacity in healthy subjects and MS subtypes. In MS organoids, particularly in PPMS, we observed a decrease in p21 expression associated with a dysregulation of PAK1 and E2F1 expression. In parallel, a decrease in oligodendrocyte maturation was detected in long-term cultured cerebral and spinal cord organoids, especially in PPMS, leading to a reduced myelination capacity. Disruption of astrocyte and neuronal populations was also observed. Our findings demonstrate that in MS, inherent deficits in the p21 pathway may alter glial and neuronal cell populations and may contribute to the disease pathogenesis by reducing the capacity for myelin repair.Summary StatementUsing cerebral and spinal cord organoids derived from multiple sclerosis patients, we found an innate disruption of oligodendrocyte differentiation and myelination capacity as well as excitotoxicity, associated with PAK1 and E2F1-induced p21 dysregulation.
Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures
Authors: Periyakoil Preethi K. , Smith Melanie H. , Kshirsagar Meghana , Ramirez Daniel , DiCarlo Edward F. , Goodman Susan M. , Rudensky Alexander Y. , Donlin Laura T. , Leslie Christina S. 
Published: January 2025

AbstractSingle-cell RNA sequencing studies have revealed the heterogeneity of cell states present in the rheumatoid arthritis (RA) synovium. However, it remains unclear how these cell types interact with one anotherin situand how synovial microenvironments shape observed cell states. Here, we use spatial transcriptomics (ST) to define stable microenvironments across eight synovial tissue samples from six RA patients and characterize the cellular composition of ectopic lymphoid structures (ELS). To identify disease-relevant cellular communities, we developed DeepTopics, a scalable reference-free deconvolution method based on a Dirichlet variational autoencoder architecture. DeepTopics identified 22 topics across tissue samples that were defined by specific cell types, activation states, and/or biological processes. Some topics were defined by multiple colocalizing cell types, such as CD34+fibroblasts and LYVE1+macrophages, suggesting functional interactions. Within ELS, we discovered two divergent cellular patterns that were stable across ELS in each patient and typified by the presence or absence of a “germinal-center-like” topic. DeepTopics is a versatile and computationally efficient method for identifying disease-relevant microenvironments from ST data, and our results highlight divergent cellular architectures in histologically similar RA synovial samples that have implications for disease pathogenesis.
Escherichia coliouter membrane vesicles encapsulating small molecule antibiotics improve drug function by facilitating transport
Authors: Wu Meishan , Harrower Rachael M. , Li Ziang , Brown Angela C. 
Published: January 2025

AbstractThe development of novel antimicrobial agents that are effective against Gram-negative bacteria is hindered by the dual membrane cell wall structure of these bacteria. To reach their intracellular targets, most antibiotics must therefore pass through protein channels called porins; however, a common mechanism of acquired resistance is decreased expression of these proteins. Inspired by the ability of outer membrane vesicles (OMVs) to deliver cargo to the bacterial cytosol, we hypothesized that encapsulation of small molecule antibiotics within OMVs would improve the activity of the drugs by facilitating uptake. To test this, we investigated the ability of antibiotic- encapsulated OMVs to inhibit the growth of both Gram-negative and Gram-positive bacteria, including multidrug-resistant clinical isolates. We also demonstrated that this mechanism of delivery does not require porin expression. Together, our results demonstrate the potential of OMVs as novel antibiotic delivery vehicles to treat antibiotic-resistant bacterial infections.
C12ORF57: a novel principal regulator of synaptic AMPA currents and excitatory neuronal homeostasis
Authors: Jiang Ruiji , Chouchane Malek , Moey Ching , Bunt Jens , Li Jiang , Alkuraya Fowzan , Alobeid Eman , Richards Linda , Ullian Erik , Sherr Elliott 
Published: January 2025

AbstractBiallelic recurrent loss of function mutations inC12ORF57, a novel open reading frame, underlie Temtamy syndrome (TS)—a neurodevelopmental disorder characterized by dysgenesis of the corpus callosum, epilepsy, and severe intellectual disability. Investigate the function of this gene, we used a knockout (KO) mouse model of its murine ortholog,Grcc10.Grcc10KO mice exhibit the characteristic phenotypic features seen in human TS patients, including increased epileptiform activity. Corresponding with this seizure susceptibility, hippocampal neurons in these mice exhibited significantly increased AMPA receptor expression levels and higher amplitude of miniature excitatory postsynaptic currents (mEPSCs). We also find that GRCC10/C12ORF57 modulates the activity of calcium/calmodulin dependent kinase 4 (CAMK4) and regulates the expression of CREB and ARC, which are involved in the synaptic scaling of AMPA receptors. Through multiple lines of inquiry, we establish that C12ORF57/GRCC10 plays a central modulatory role in synaptic homeostasis and uncover a novel mechanism for neuronal excitatory tuning.
Replay builds an efficient cognitive map offline to avoid computation online
Authors: Ou Jianxin , Qu Yukun , Xu Yue , Xiao Zhibing , Behrens Tim , Liu Yunzhe 
Published: January 2025

AbstractHow do humans integrate fragmented experiences into a coherent structure for novel inferences? Although offline replay is proposed to reorganize memories, whether it constructs an integrated cognitive map remains unclear. Using magnetoencephalography, we tracked neural activity as participants learned one-dimensional, pairwise rank relationships that together formed a two-dimensional (2D) conceptual map, and then inferred unobserved relationships. Offline replay during rest integrated piecemeal memories into a 2D representation, predicting future inference accuracy. This offline replay and fast on-task replay during inference correlated with grid-cell-like code, representing a generalizable schema that minimized effortful online computations. In contrast, slow on-task replay focusing on trial-specific details, negatively correlated with grid-like codes and inference performance. Together, replay builds an efficient cognitive map offline, reducing reliance on deliberate computations online.
Social dysfunction relates to altered default mode network functional integrity across neuropsychiatric disorders: A replication and generalization study
Authors: Braak Simon , Mennes Maarten , Su Tanja , Pijnenburg Yolande , Bakker Geor , Arango Celso , van der Wee Nic , Bauduin Stéphanie , Moya Ana Ortiz-Tallo , Lopez-Morinigo Javier-David , Dawson Gerard R. , Abrahams Abigail B. , Beckenstrom Amy Christine , Beckmann Christian F. , Marston Hugh M. , Penninx Brenda W.J.H. , Kas Martien J. H. 
Published: January 2025

AbstractBackgroundSocial dysfunction is an early manifestation of neuropsychiatric disorders that may relate to altered Default Mode Network (DMN) integrity. This study aimed to replicate previous findings linking social dysfunction with diminished resting-state DMN functional connectivity and altered task-based DMN functional activation in response to emotional faces across schizophrenia (SZ), Alzheimer’s disease (AD), and healthy controls (HC), and to extend these findings to major depressive disorder (MDD).MethodsResting-state fMRI and task-based fMRI data on implicit facial emotional processing were acquired in an overlapping cohort (resting-state fMRI: N=167; SZ=32, MDD=44, AD=29, HC=62. Task-based fMRI: N=152; SZ=30, MDD=42, AD=26, HC=54). Additionally, mega-analyses (N=317 for resting-state fMRI; N=291 for task-based fMRI) of the current and a prior independent sample were conducted. Social dysfunction was indexed with the Social Functioning Scale (SFS) and the De Jong-Gierveld Loneliness (LON) scale.ResultsThe association between higher mean SFS+LON social dysfunction scores and diminished DMN connectivity within the dorsomedial prefrontal cortex across SZ/AD/HC participants was replicated, and extended to MDD patients. Similar observations within the dorsomedial and rostromedial prefrontal cortex were found in the mega-analysis. Associations between social dysfunction and DMN activation in response to sad and happy faces were not replicated or found in the mega-analysis.ConclusionsDiminished dorsomedial prefrontal cortex DMN connectivity emerged as a transdiagnostic neurobiological marker for social dysfunction, suggesting a potential treatment target for precision medicine approaches. DMN functional responses to emotional faces may not be a sensitive biomarker for social dysfunction.