bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic reprogramming induced by Acetyl-CoA and SAM depletion is an evolutionarily-ancient path to malignant growth
Authors: Chen Zhe , Zhang Xiaomeng , Deng Mingxi , Li Chongyang , Nguyen Thi Thuy , Liu Min , Dou Kun , Ishibashi Toyotaka , Wang Jiguang , Yan Yan 
Published: December 2024

AbstractDespite the vast diversity of life forms and living histories, it appears that all branches of Metazoa face the challenge of tumor growth. Contrary to human tumors, which take years to form, tumors in short-living species can arise within days without accumulating multiple mutations, raising the question whether the paths to tumorigenesis in diverse species have any commonalities.In a fly tumor model caused by loss of cell polarity genes, we first identified the rise of a glycolytic cell population over time, resembling the Wartburg effect observed in human tumors. We further identified two key metabolic changes in these fly tumors. First, a systemic depletion of acetyl-CoA leads to a reduction in histone acetylation levels and stochastic silencing of actively-transcribed genes. Second, defects in the methionine cycle cause a systemic depletion of S-Adenosyl methionine, which further reduces histone methylation levels and causes stochastic activation of transposons. Perturbation of the methionine metabolic process strongly inhibits tumor growth. Finally, to understand the evolutionary origin of tumorigenesis, we performed comparative studies of fly and human tumors, and identified human tumors that exhibit metabolic signatures similar to those of fly tumors. We found that human tumors with high metabolic similarity to fly tumors have a lower mutational load, younger patient age, and lower DNA methylation levels. This study suggests that tumorigenesis processes have a deep evolutionary origin and highlights that depletion of key metabolites is an evolutionarily-ancient driving force for tumorigenesis.
Mitochondrial adenine base editing of mouse somatic tissues via adeno-associated viral delivery
Authors: Mutti Christian D. , Van Haute Lindsey , Luengo-Gutierrez Lucia , Turner Keira , Silva-Pinheiro Pedro , Minczuk Michal 
Published: December 2024

AbstractThe development of adenine base editing in mitochondria, alongside cytidine base editing, has significantly expanded the genome engineering capabilities of the mitochondrial DNA. We tested the recent advancements in adenine base editing technology using optimised TALEs targeting genesMt-Cytb, Mt-CoIIandMt-Atp6in mouse cells, and observed successful A:T to G:C conversions within the target windows of each gene. Then, we used the best performing pairs targeting theMt-Atp6gene to inject mice using adeno-associated viral delivery to post-mitotic tissue. We observed limited efficiency of adenine edits in mouse somatic tissue after 4 weeks, suggesting the necessity of further optimisation of this technology.
Dopamine regulates the membrane potential and glycine release of AII amacrine cells via D1-like receptor modulation of gap junction coupling
Authors: Strazza Junior Paulo , Wakeham Colin M , von Gersdorff Henrique 
Published: December 2024

AbstractDopamine plays a pivotal role in adjusting the flow of information across the retina as luminance changes from night to day. Here we show, under dim photopic conditions, that both dopamine and a D1-like receptor (D1R) agonist hyperpolarized the resting membrane potential (Vm) of AII amacrine cells (AII-ACs). Surprisingly, in the presence of glutamatergic and GABAergic synaptic blockers that isolate glycinergic synapses, D1R agonists are without effect. However, a D1R antagonist depolarized Vmand reduced the input resistance of AII-ACs in wild type mice, but not inCx36−/−mice. Accordingly, D1R antagonists enhanced tonic glycinergic transmission to type-2 OFF-cone bipolar cells (OFF-CBCs). D1Rs thus adjust the Vmand excitability of AII-ACs and, thereby, the level of glycine release to OFF-CBCs by regulating gap junction coupling with ON cone bipolar cells. Our findings provide insights into how the retina may use dopamine to adapt crossover inhibitory microcircuits during changes in luminance.
The applying of immuno-RCA for the high-sensitivity detection of the ABO blood group antibodies on the printed glycoarray
Authors: Kornilova E.E. , Kutukov R.R. , Polyakova S.M. , Nokel A.Yu. , Zavriev S.K. , Ryazantsev D.Yu. 
Published: December 2024

AbstractDetecting small amounts of analytes, especially antibodies, presents a significant challenge in high-throughput methods. Fortunately, nucleic acid amplification techniques provide a promising solution. We have successfully developed and tested an innovative technology for detecting anti-glycan antibodies, utilizing a printed glycan array combined with a rolling circle amplification reaction based on the ABO blood group antibody model. This breakthrough has dramatically enhanced the sensitivity of our immunoassay, improving it by over an order of magnitude and allowing us to detect concentrations as low as 1 ng/ml. This advancement opens new approaches for research and clinical applications, making previously undetectable analytes accessible for study.
Chromosomal plasticity can drive rapid adaptation in bacteria
Authors: Vega-Cabrera Luis , Skovgaard Ole , Toll-Riera Macarena 
Published: December 2024

ABSTRACTUnderstanding the molecular mechanisms underlying rapid adaptation to stress is a fundamental question in evolutionary biology. A common mechanism is copy number changes, which can affect single genes, larger genomic regions, or even entire chromosomes in the case of eukaryotes (aneuploidy). Bacterial species with genomes comprising more than one chromosome are common, yet the role of adaptive copy number changes affecting entire chromosomes is unknown. Here, by using a bacterium with two chromosomes (chrI and chrII) as model system and combining evolution experiments in the presence of severe nutrient stress with whole-genome sequencing, we show that chromosomal copy number changes can drive rapid adaptation. We detected increased copy number of the entire chrII in almost half of the sequenced clones, isolated from twelve independent populations. In most cases, copy number increases were driven by mutations in the replication protein of chrII. A higher chrII copy number is likely to be beneficial because chrII codes for the operon responsible for metabolizing D-gluconic acid, the only carbon source present in the medium. Our results revealed a novel mechanism for rapid adaptation in bacteria. Given the prevalence of bacteria with secondary chromosomes, and the enrichment of secondary chromosomes in genes associated with interaction with the environment, this may be an important mechanism for adapting to novel environments that has been overlooked.
High cumulative viral titers of influenza virus in animals with significant disease fatality rates indicate a potential trade-off between fatality and transmissibility
Authors: Gouveia Ayrton S. , Mata Leonardo G. , Villela Daniel A.M. 
Published: December 2024

AbstractEvaluating the trade-off hypothesis for the evolution of virulence using empirical data poses significant challenges. The hypothesis suggests that pathogens evolve to maximize transmissibility, but fatality imposes limits as there are diminishing gains in transmissibility. In this study, we analyzed a secondary dataset of influenza virus infections in ferrets (Mustela putorius furo), categorized by Hemagglutinin (HA) and Neuraminidase (NA) subtypes. Subgroups defined by the H7/N9 and H7/N7 combinations exhibited fatality rates of approximately 30% and reached cumulative viral titers close to 7.5 (log10titer/mL). These levels represent intermediate fatality rates, as the H5/N6 and H5/N1 subgroups had higher fatality rates but reached lower cumulative viral titers. Using cumulative viral titer as a proxy for potential secondary transmissions, the analysis suggests that intermediate fatality rates are associated with higher numbers of secondary transmissions. However, there are significant uncertainties in subgroups with lower or no fatalities. Additionally, subgroups without fatalities showed substantial variability in cumulative viral titers.
Comprehensive expression data for two honey bee species,Apis melliferaandApis cerana japonica
Authors: Yokoi Kakeru , Hatakeyama Masatsugu , Kuwazaki Seigo , Maeda Taro , Yoshiyama Mikio , Horigane-Ogihara Mari , Matsuyama Shigeru , Jouraku Akiya , Bono Hidemasa , Kimura Kiyoshi 
Published: December 2024

AbstractComprehensive expression datasets were constructed forApis melliferaandApis cerana japonica. Post-oviposition day 6 to day 58 samples ofA. melliferaworkers (larva to adult); day 9, 10, 12, and 13 samples ofA. melliferaqueen (larva to pupa); and day 9 to day 18 samples ofA. cerana japonicaworkers (larva to adult) were prepared, and RNA-Seq data were obtained. ForA. cerana japonica, reference transcript sequence data, predicted amino acid sequence data, and functional annotation data were generated based on the genome sequence and RNA-Seq data. Using the transcript sequence and RNA-Seq data, comprehensive expression data for all transcripts ofA. mellifera and A. cerana japonicawere prepared. Hierarchical clustering analyses and the used sample preparation method ensured that both sets of expression data were reliable for use as comprehensive reference expression datasets. Therefore, these data are applicable for honey bee research or for comparative or evolutionary studies on insect species or social insect species at the genetic and molecular levels.
Classification of Visual Imagery and Imagined Speech EEG based Brain Computer Interfaces using 1D Convolutional Neural Network
Authors: Le Diane 
Published: December 2024

AbstractNon-invasive brain-computer interfaces (BCI) utilising electroencephalogram (EEG) signals are a current popular, affordable and accessible method for establishing communication paths between the mind and external devices. However, the challenges faced are inter-subject variability, BCI illiteracy and poor machine learning decoding performance. Two emerging intuitive mental paradigms, Visual Imagery (VI) and Imagined Speech (IS) show promise to optimise the development of non-invasive BCIs, which involves the extraction of corresponding neural patterns during the imagined tasks. This study took a comprehensive user-centric approach to build on the current foundation of knowledge on VI and IS EEG-BCIs utilising an adapted 1D-CNN to optimise the classification decoding performance. Twenty healthy participants were assessed for their ability to visualise imagery in their minds and performed the VI and IS mental paradigms in two class conditions “push” and “relax”. It was shown that alpha and beta suppression was observed during the “push” condition of VI compared to the “relax” condition, and those that scored higher in the VVIQ had better VI classification accuracy than those who did not. The adapted 1D-CNN model performed well for classification between the two classes “push” and “relax” at 89.3% and 77.87% performance accuracy for VI and IS, respectively. These findings contribute to the current body of work on VI BCI, that it is a dynamic and plausible option compared to standard BCI paradigms, and VI BCI illiteracy could potentially be controlled by VVIQ. It also demonstrated the potential of the 1D-CNN model in classification of VI and IS EEG-BCIs.
CRISPR-Edited DPSCs, Constitutively Expressing BDNF Enhance Dentin Regeneration in Injured Teeth
Authors: Kim Ji Hyun , Irfan Muhammad , Sreekumar Sreelekshmi , Kim Stephanie , Phimon Atsawasuwan , Chung Seung 
Published: December 2024

AbstractDental caries is one of the most common health issues worldwide arising from the complex interactions of bacteria. In response to harmful stimuli, desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associated with significant inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs). Previously, we have shown that brain-derived neurotrophic factor (BDNF) and its receptor TrkB, key mediators of neural functions, are activated during the DPSC-mediated dentin regeneration process. In this study, we further define the role of inflammation in this process and apply stem cell engineering to enhance dentin regeneration in injured teeth. Our data show that TrkB expression and activation in DPSCs rapidly increase during odontogenic differentiation, further amplified by inflammatory inducers and mediators such as TNFα, LTA, and LPS. An in vivo dentin formation assessment was conducted using a mouse pulp-capping/caries model, where CRISPR-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. This transplantation significantly enhanced dentin regeneration in injured teeth. To further explore potential downstream pathways, we conducted transcriptomic profiling of TNFα-treated DPSCs, both with and without TrkB antagonist CTX-B. The results revealed significant changes in gene expression related to immune response, cytokine signaling, and extracellular matrix interactions. Taken together, our study advances our understanding of the role of BDNF in dental tissue engineering using DPSCs and identifies potential therapeutic avenues for improving dental tissue repair and regeneration strategies.
Universal Study Design for Instrument Changes in Pharmaceutical Release Analytics
Authors: Ries Anne B. , Merkel Maximilian N. , Coßmann Kristina , Paul Marina , Grunwald Robin , Klemmer Daniel , Hübner Franziska , Eggensperger Sabine , Weiß Frederik T. 
Published: December 2024

AbstractInstrument changes in analytical methods of pharmaceutical quality control are required to maintain release analytics over decades, yet typically pose a challenge.We designed an efficient instrument comparability study to gain a comprehensive understanding of potential performance differences between instruments and therefore rationalize the risk assessment and decision process for a path forward. The results may either point out whether a full or partial re-validation is necessary or whether a science-based bridging can be pursued based on the data generated in the study. The study design is universally applicable to a substantial range of release analytical methods. In a straightforward setup of two experiments with the new instrument, a statistically meaningful data set is generated for comparison with available historical or validation data of the original instrument.In a Good Manufacturing Practice (GMP) environment, we realized the study design a first benchmark in imaged capillary isoelectric focusing (icIEF) analytics, comparing the ICE3 and Maurice C instruments. The core-study confirmed equal or better performance of Maurice C in all parameters and serves as a basis for seamless continuation of release measurements on Maurice C.
14-3-3ε inhibits premature centriole disengagement by inhibiting the activity of Plk1 and Separase
Authors: Jaiswal Monika A. , Karn Akshay , Das Aparna , Kumari Anisha , Tiwari Shilu , Dalal Sorab N. 
Published: December 2024

ABSTRACTThe 14-3-3 protein family regulates several pathways in mammalian cells, including centrosome duplication. However, the precise mechanisms by which 14-3-3 paralogs regulate the centrosome cycle remain unclear. To identify the mechanisms by which 14-3-3ε regulates centrosome duplication, we altered two conserved acidic residues in the 14-3-3ε phospho-peptide-binding pocket that regulate complex formation and dissociation with the associated ligands, D127 and E134, to Alanine. Altering these residues to Alanine led to opposing effects on centrosome duplication; the D127A mutant inhibited centrosome duplication, while cells expressing the E134A mutant showed the presence of supernumerary centrosomes. We demonstrate that 14-3-3ε does not inhibit centriole duplication, as reported for 14-3-3γ, but inhibits centriole disengagement. Using a combination of pharmacological and genetic approaches, we demonstrate that 14-3-3ε inhibits the activity of Plk1 and Separase, leading to disengagement defects that ultimately lead to decreased proliferation and cell death. Our work demonstrates that different 14-3-3 paralogs regulate different steps in the centrosome cycle, and disrupting complex formation between 14-3-3ε and Plk1 or Separase could be a novel therapeutic strategy in tumor cells.
Pan-cancerN-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers
Authors: Govindarajan Meinusha , Mejia-Guerrero Salvador , Chafe Shawn C , Khan Shahbaz , Shi Wei , Waas Matthew , Khoo Amanda , Liu Lydia Y , Ignatchenko Vladimir , Principe Simona , Sepiashvili Lusia , Tatari Nazanin , Venugopal Chitra , Miletic Petar , Topley Maxwell , Grewal Shan , McKenna Dillon , Sandi Maria-Jose , Pham Nhu-An , Casey Alison , Kim Hyeyeon , Karamboulas Christina , Meens Jalna , Bergqvist Peter , Silva Begonia , Chan Patrick , Cerna-Portillo Liza , Chin Jasmine , Rao-Bhatia Abilasha , Tsao Ming-Sound , Khokha Rama , Su Susie , Xu Wei , Goldstein David , Ailles Laurie , Stambolic Vuk , Liu Fei-Fei , Cummins Emma , Samudio Ismael , Singh Sheila K , Kislinger Thomas 
Published: December 2024

SUMMARYCell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central role in cellular signaling. Despite this, their promise remains largely untapped due to the technical challenges inherent to profiling cell surface proteins. Here, we employedN-glycoproteomics to analyze 85 patient-derived xenografts (PDX), constructing Glyco PDXplorer – anin vivopan-cancer atlas of cancer-derived cell surface proteins. We developed a target discovery pipeline to prioritize proteins with favorable expression profiles for immunotherapeutic targeting and validated FAT2 as a head and neck squamous cancer (HNSC) enriched surface protein with limited expression in normal tissue. Functional studies revealed that FAT2 is essential for HNSC growth and adhesion through regulation of surface architecture and integrin-PI3K signaling. Chimeric antigen receptor (CAR) T cells targeting FAT2 demonstrated potent anti-tumor activity in HNSC models. This work lays the foundation for developing FAT2-targeted therapies and represents a pivotal resource to inform therapeutic target discovery for multiple cancers.HIGHLIGHTSPan-cancer landscape of cancer-derived cell surface proteins detectedin vivoDevelopment of a multi-omic discovery pipeline to prioritize proteins with optimal expression profiles as immunotherapy targetsIdentification and validation of FAT2 as a head and neck squamous cancer enriched surface protein with minimal expression in normal tissuesFAT2 coordinates cell surface organization, adhesion, growth and survival through the integrin-PI3K-AKT pathwayFAT2 CAR T cells demonstrate anti-tumour activity in pre-clinical models
Long-read Transcriptomics of Caviid Gammaherpesvirus 1: Compiling a Comprehensive RNA Atlas
Authors: Torma Gábor , Dörmő Ákos , Fülöp Ádám , Tombácz Dóra , Mizik Máté , Pretory Amanda M. , Lee See-Chi , Toth Zsolt , Boldogkői Zsolt 
Published: December 2024

ABSTRACTCaviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to KSHV, and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis.IMPORTANCEThe molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.
Data-driven synapse classification reveals a logic of glutamate receptor diversity
Authors: Micheva Kristina D. , Simhal Anish K. , Schardt Jenna , Smith Stephen J , Weinberg Richard J. , Owen Scott F. 
Published: December 2024

AbstractThe rich diversity of synapses facilitates the capacity of neural circuits to transmit, process and store information. We used multiplex super-resolution proteometric imaging through array tomography to define features of single synapses in mouse neocortex. We find that glutamatergic synapses cluster into subclasses that parallel the distinct biochemical and functional categories of receptor subunits: GluA1/4, GluA2/3 and GluN1/GluN2B. Two of these subclasses align with physiological expectations based on synaptic plasticity: large AMPAR-rich synapses may represent potentiated synapses, whereas small NMDAR-rich synapses suggest “silent” synapses. The NMDA receptor content of large synapses correlates with spine neck diameter, and thus the potential for coupling to the parent dendrite. Overall, ultrastructural features predict receptor content of synapses better than parent neuron identity does, suggesting synapse subclasses act as fundamental elements of neuronal circuits. No barriers prevent future generalization of this approach to other species, or to study of human disorders and therapeutics.