bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLOWORM-META: Modelling gastrointestinal nematode metapopulation dynamics to inform cattle biosecurity research
Authors: Ingle Olivia K. , Melville Lynsey A. , Beechener Sam , Hardy Claire , Howell Alison , Hobbs Neil P. , Mahon Niamh , Morgan Eric R. , Bartley David , Vineer Hannah Rose 
Published: February 2025

AbstractGastrointestinal nematode (GIN) parasite infections in grazing livestock cause significant disease, and are responsible for estimated annual losses of over €1.8 billion in Europe alone. The management of GINs in cattle is threatened by anthelmintic drug resistance (AR). Immediate action is needed to slow the progression of AR in cattle GINs and avoid the increasingly common scenario of multiple drug resistance seen in sheep. Although AR can arise independently on multiple farms, it may also be spread between holdings via purchased cattle. Therefore, effective biosecurity measures on cattle enterprises could help to reduce the risk of establishment of AR populations. A metapopulation model was developed and validated for two GIN species infecting cattle,Ostertagia ostertagiandCooperia oncophora, incorporating the full parasite life cycle, weather- and immunity-dependent parasite life history traits and multiple pasture sub-populations. This allowed for complex grazing management strategies and weather influences to be simulated. The models successfully replicated the seasonal patterns and intensity of infections reported in multiple published longitudinal datasets. Global sensitivity analysis against four Quantities of Interest (QoIs) related to factors affecting the safety of the resident herd and of the purchased animals was used to quantify the influence of candidate biosecurity measures. The duration of quarantine, the date of purchase (weather/seasonal influences) and the intensity of infection on the day of purchase strongly influenced the QoIs. The outcomes for the UK were not significantly influenced by the geographic location of the purchasing farm, suggesting that the influence of weather patterns on GIN populations outweighs that of regional climate differences, and thus regional variations to GIN biosecurity recommendations are not warranted without alternative evidence to support this. The model presented here is the first full lifecycle GIN metapopulation model forO. ostertagiandC. oncophora, validated against longitudinal field data, and can be broadly used to evaluate the relative efficacy of a range of cattle GIN management strategies, as demonstrated here. These findings offer valuable insights to focus initial biosecurity recommendations for cattle enterprises, and are being used to direct qualitative and quantitative research to refine recommendations.HighlightsA metapopulation model for cattle GINs was developedThe model includes weather-dependence and complex grazingThe model replicated seasonal infection patterns from multiple datasetsSensitivity analysis explored influential biosecurity measuresThe influence of weather outweighed that of geographic location (climate)Initial recommendations for biosecurity and further research are made
Coding of the basic components of subjective value in primate dopamine neurons: subjectively weighted reward amount and probability
Authors: Ferrari-Toniolo Simone , Seak Leo Chi U , Schultz Wolfram 
Published: February 2025

ABSTRACTBehavioral choices of uncertain rewards suggest that agents construct subjective reward value by combining the basic value components of utility and weighted probability. Despite the general acceptance of this evaluation mechanism for explaining economic choice, knowledge about its neuronal implementation is fractionated and remains essentially unknown. We investigated in monkeys whether reward signals in dopamine neurons might represent subjective reward value based on these two fundamental value components. Despite some heterogeneity across individual neurons, the dopamine population signal reliably represented the axiomatically defined integration of utility and weighted probability into subjective value in a way that closely matched the animal-specific choice behavior. In particular, we identified a crucial contribution of subjectively weighted probability to the dopamine signal of subjective reward value. These data demonstrate a neuronal implementation of subjective value constructed from the two most basic subjective reward components.Preprint ServerAn earlier version of this manuscript has been uploaded to bioRxiv in February 2025 (CC-BY).
Caspase-dependent ablation of indirect medium spiny neurons projecting to external globus pallidus promotes compulsive ethanol-seeking and drinking behaviors
Authors: Haroon Humza , Baker Matthew , Choi Doo-Sup 
Published: February 2025

AbstractThe dorsomedial striatum (DMS) is primarily recognized for regulating goal-directed reward-seeking behaviors, while the dorsolateral striatum (DLS) is predominantly associated with movement and habitual behaviors. In this study, we sought to investigate two pathways, direct medium spiny neuron (dMSN) and indirect medium spiny neuron (iMSN) in the two dorsal striatal subregions (DMS and DLS) in ethanol-seeking and drinking behaviors. Here, we selectively ablated iMSNDMS→GPeand iMSNDLS→GPeand trained mice to exhibit goal-directed and habitual reward-seeking behaviors using random ratio (RR) and random interval (RI) operant conditioning, respectively. We found that partial ablation of iMSNDLS→GPeexhibited increased resilience to bitter-tasting ethanol solution when subjected to quinine adulterated reward in operant conditioning paradigms, suggesting compulsive-like seeking behavior. Consistently, in a separate cohort of mice, we found that the iMSNDLS→GPeablated mice show higher preference and consumption of quinine adulterated ethanol solution than control mice in two-bottle choice continuous access drinking, with increasing quinine concentration and exhibit more compulsive-like behavior. On the other hand, ablation of iMSNDMS→GPeresulted in insensitivity to satiety-based reward devaluation in RR-trained mice, consistent with a shift toward habitual behavior but no change in compulsive ethanol-seeking and drinking behavior. Together, our findings demonstrate that DLS iMSN function is essential in inhibiting compulsive-like behavior.
Satiety, TAX-4, and OSM-9 Tune the Attraction ofC. elegansNematodes to Microbial Fermentation Products
Authors: Logan-Garbisch Theresa , Fryer Emily , Seyahi Lara Selin , Rogel-Hernandez Lucero , Rhee Seung Y. , Goodman Miriam B. 
Published: February 2025

AbstractAnimals are sensitive to selective pressures associated with nutrient acquisition, underscoring the evolutionary significance of chemosensation in foraging and its intersection with satiety. For the model nematodeCaenorhabditis elegans, isoamyl alcohol (3-methyl-1-butanol) and 2-methyl-1-butanol are produced by microbial fermentation and present in bacterial food sources collected from the natural environments. Both compounds, which are structural isomers of one another, elicit strong attraction in laboratory settings. Using laboratory chemotaxis assays, we show that starvation attenuates attraction to both compounds. Well-fedC. elegansis largely insensitive to the biosynthetic precursors of both alcohols, with the exception of 4-methyl-2-oxovaleric acid, which is a mild repellent.C. eleganschemosensation relies on expression oftax-4cyclic nucleotide-gated (CNG) andosm-9transient receptor potential, vanilloid (TRPV) ion channels and animals lacking both genes are taste- and smell-blind. Animals lackingtax-4fail to attract isoamyl alcohol and 2-methyl-1-butanol and those lackingosm-9exhibit stronger attraction than the wild-type. Starvation not only attenuates attraction, but also enhances repulsion to 4-methyl-2-oxovaleric acid and uncovers repulsion intax-4mutants absent in their well-fed counterparts. Collectively, these findings implicate satiety in regulating response strength,tax-4-dependent chemotaxis in attraction to isoamyl alcohol and 2-methyl-1-butanol, andosm-9-dependent chemotaxis in suppressing responses to biosynthetic precursors.
Context-Dependent and Gene-Specific Role of Chromatin Architecture Mediated by Histone Modifiers and Loop-extrusion Machinery
Authors: Tastemel Melodi , Jussila Adam , Saravanan Bharath , Huang Hui , Xie Yang , Zhu Quan , Jiang Yifan , Armand Ethan , Ren Bing 
Published: February 2025

AbstractLoop-extrusion machinery, comprising the cohesin complex and CCCTC-binding factor CTCF, organizes the interphase chromosomes into topologically associating domains (TADs) and loops, but acute depletion of components of this machinery results in variable transcriptional changes in different cell types, highlighting the complex relationship between chromatin organization and gene regulation. Here, we systematically investigated the role of 3D genome architecture in gene regulation in mouse embryonic stem cells under various perturbation conditions. We found that acute depletion of cohesin or CTCF disrupts the formation of TADs, but affects gene regulation in a gene-specific and context-dependent manner. Furthermore, the loop extrusion machinery was dispensable for transcription from most genes in steady state, consistent with prior results, but became critical for a large number of genes during transition of cellular states. Through a genome-wide CRISPR screen, we uncovered multiple factors that can modulate the role of loop extrusion machinery in gene regulation in a gene-specific manner. Among them were the MORF acetyltransferase complex members (Kat6b, Ing5, Brpf1), which could antagonize the transcriptional insulation mediated by CTCF and cohesin complex at developmental genes. Interestingly, inhibition of Kat6b partially rescues the insulator defects in cells lacking the cohesin loader Nipbl, mutations of which are responsible for the developmental disorder Cornelia de Lange syndrome. Taken together, our findings uncovered interplays between the loop extrusion machinery and histone modifying complex that underscore the context-dependent and gene-specific role of the 3D genome.
First Successful Targeted Mutagenesis Using CRISPR/Cas9 in Stably Transformed Grain Amaranth Tissue
Authors: Vollmer Susanne K , Stetter Markus G , Hensel Götz 
Published: February 2025

SummaryGenome editing using CRISPR/Cas is a key technology for speeding up breeding for climate-resilient, high-yielding crops (Schebenet al., 2017). However, efficient targeted mutagenesis requires implementing stable transformation methods and establishing a CRISPR/Cas setup suitable for the species of interest (Shanet al., 2020). The availability of such methods is a significant bottleneck to advancing many promising, albeit under-researched, crops. Testing and establishing vectors for efficient application of CRISPR/Cas in non-model crops could boost research and breeding of new valuable crops (Ye and Fan, 2021).We edited key pathway genes in the betalain biosynthesis pathway of grain amaranth, i.e.,A. hypochondriacus L., to prove how targeted mutagenesis can be implemented in an orphan crop using the CasCADE modular cloning system (Hoffie, 2022). Grain amaranth is a resilient C4dicot orphan crop with excellent nutritional composition. These properties make amaranth a well-suited candidate to be bred as a climate-resilient crop (Joshiet al., 2018). However, no efficient and reproducible protocol for successful application of CRISPR/Cas9 or stable transformation and regeneration, has been demonstrated inA. hypochondriacus(Castellanos-Arévaloet al., 2020).
Dynamic reconfiguration of brain coactivation states associated with active and lecture-based learning of university physics
Authors: Smith Donisha D. , Bartley Jessica E. , Peraza Julio A. , Bottenhorn Katherine L. , Nomi Jason S. , Uddin Lucina Q. , Riedel Michael C. , Salo Taylor , Laird Robert W. , Pruden Shannon M. , Sutherland Matthew T. , Brewe Eric , Laird Angela R. 
Published: February 2025

AbstractAcademic institutions are increasingly adopting active learning methods to enhance educational outcomes. Using functional magnetic resonance imaging (fMRI), we investigated neurobiological differences between active learning and traditional lecture-based approaches in university physics education. Undergraduate students enrolled in an introductory physics course underwent an fMRI session before and after a 15-week semester. Coactivation pattern (CAP) analysis was used to examine the temporal dynamics of brain states across different cognitive contexts, including physics conceptual reasoning, physics knowledge retrieval, and rest. CAP results identified seven distinct brain states, with contributions from frontoparietal, somatomotor, and visuospatial networks. Among active learning students, physics learning was associated with increased engagement of a somatomotor network, supporting an embodied cognition framework, while lecture-based students demonstrated stronger engagement of a visuospatial network, consistent with observational learning. These findings suggest significant neural restructuring over a semester of physics learning, with different instructional approaches preferentially modulating distinct patterns of brain dynamics.
Triosephosphate Isomerase as a Quantum Logic Gate: Could quantum decoherence be toxic?
Authors: Romanello Daniele , Romanello Andrea 
Published: February 2025

AbstractThis study presents the hypothesis that triosephosphate isomerase (TIM), a pivotal enzyme in glycolysis, functions as a quantum logic gate. Utilizing quantum mechanics, we model TIM’s catalytic conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P) as a quantum operation involving precise proton transfer. To explore the broader implications of this quantum behavior, we developed a quantum model to assess the impact of Sodium-glucose co-transporter 2 inhibitors (SGLT2i) on methylglyoxal formation, a toxic byproduct linked to advanced glycation end products (AGEs). Our model predicts that SGLT2i could reduce methylglyoxal by decreasing the likelihood of intermediate formation, providing a potential mechanism for their protective effects observed in clinical contexts, including vascular and renal protection in diabetes, nephropathy, and heart failure. By reframing TIM as a quantum logic gate, this study not only challenges traditional views of enzymatic function but also opens new avenues for quantum biology, offering profound implications for the future of metabolic disease research and drug development. Moreover considering methylglyoxal as a result of a quantum tunnel inefficiency, it’s possible to hypothesize a new “noxa patogena” explicating it’s action as quantum interference.
SARS-CoV-2 nucleocapsid uniquely disrupts chromatin over pathophysiologically relevant gene promoters
Authors: Benoit Jane M , Dennis Jonathan H 
Published: February 2025

AbstractSARS-CoV-2, the causative agent of COVID-19, is a positive-sense, single-stranded RNA virus that causes a spectrum of disease severity, from asymptomatic infection to severe illness to long-term sequelae. Similar to other human coronaviruses, SARS-CoV-2 proteins modulate host genomic responses through epigenomic modifications, facilitating viral replication and immune evasion. While the nucleocapsid protein is well known for its role in RNA stability and immune modulation, its impact on host chromatin organization remains unclear. To investigate this, we generated stable human alveolar cell lines expressing nucleocapsid proteins from endemic and pandemic human coronaviruses. Our analysis revealed that nucleocapsid proteins from all tested coronaviruses induced changes in nucleosome positioning and occupancy at specific gene promoters involved in coagulation pathways, hormone signaling, and innate immune responses. Additionally, SARS-CoV-2-specific alterations were identified in genes dysregulated in severe infections, suggesting a direct role for epigenomic modifications in disease pathophysiology. We also observed extensive changes in nucleosome susceptibility to nuclease digestion in SARS-CoV and SARS-CoV-2 samples that were not observed in common cold cell lines. Promoters with altered sensitivity and resistance to nuclease were linked to innate immune, metabolic, olfactory, and signaling pathways known to be dysregulated in severe COVID-19 and post-acute sequelae (PASC). These findings demonstrate that nucleocapsid protein expression alters chromatin structure at specific loci, implicating viral proteins in host genome dysregulation. Furthermore, we identified both shared and unique chromatin targets of SARS-CoV-2 and common cold coronaviruses, highlighting pathways for further investigation and potential therapeutic intervention.ImportanceHost chromatin is known to be modulated by coronaviruses during infections. However, the role of the nucleocapsid protein in these alterations are unknown. Here, we show that nucleocapsids from seven human coronaviruses alter nucleosome distribution and susceptibility to enzymatic digestion over specific gene promoters in a human lung cell line. Nucleocapsids from SARS-CoV and SARS-CoV-2 have the most prominent effects which are seen over genes involved in immune responses, metabolism, hormone signaling, and other pathways that are known to be dysregulated in severe COVID-19 and post-acute sequelae of COVID-19.Graphical abstract
Knowledge Connector: Decision support system for multiomics-based precision oncology
Authors: Hübschmann Daniel , Kreutzfeldt Simon , Roth Benjamin , Glocker Katrin , Schoop Janine , Oeser Lena , Hausmann Steffen , Koch Christian , Uhrig Sebastian , Hüllein Jennifer , Hutter Barbara , Fröhlich Martina , Heilig Christoph E. , Teleanu Maria-Veronica , Lipka Daniel B. , Kerle Irina A. , Baude Annika , Beck Katja , Heining Christoph , Glimm Hanno , Ückert Frank , Knurr Alexander , Fröhling Stefan , Horak Peter 
Published: February 2025

AbstractPrecision cancer medicine aims to improve patient outcomes by providing individually tailored recommendations for clinical management based on the evaluation of biological disease profiles in multidisciplinary molecular tumor boards (MTBs). The quality of MTB decisions depends on the comprehensive, reliable, and reproducible interpretation of increasingly complex molecular data. We developed and implemented, as part of a multicenter precision oncology program, the Knowledge Connector (KC), a decision support system that integrates individual patients’ molecular and clinical data with world knowledge to generate and document MTB recommendations. The KC supports data curation, database integration, and discussion based on multiomics data and provides an interface for creating a cross-institutional knowledge base. Furthermore, it extracts relevant biomarker-drug associations and increases the efficacy of data interpretation in a clinically relevant manner by reducing reliance on external sources and optimizing inter-curator concordance. Our results demonstrate that the KC is a versatile tool that supports medical decision-making in MTBs, thus enabling the scalability of precision cancer medicine.
Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing
Authors: Vera Axel O. , Truex Nicholas L. , Sreekanth Vedagopuram , Pentelute Bradley L. , Choudhary Amit , Raines Ronald T. 
Published: February 2025

AbstractPrecise control over the dosage of Cas9-based technologies is essential because off-target effects, mosaicism, chromosomal aberrations, immunogenicity, and genotoxicity can arise with prolonged Cas9 activity. Type II anti-CRISPR proteins (Acrs) inhibit and control Cas9 but are generally impermeable to the cell membrane due to their size (6–54 kDa) and anionic charge. Moreover, existing Acr delivery methods are long-lived and operate within hours (e.g., viral and non-viral vectors) or are not applicable in vivo (e.g., nucleofection), limiting therapeutic applications. To address these problems, we developed the first protein-based anti-CRISPR delivery platform, LFN-Acr/PA, which delivers Acrs into cells within minutes. LFN-Acr/PA is a nontoxic, two-component protein system derived from anthrax toxin, where protective antigen proteins bind receptors widespread in human cells, forming a pH-triggered endosomal pore that LFN-Acr binds and uses to enter the cell. In the presence of PA, LFN-Acr enters human cells at concentrations as low as 2.5 pM to inhibit up to 95% of Cas9-mediated knockout, knock-in, transcriptional activation, and base editing. Timing LFN-Acr delivery reduces off-target base editing and increases Cas9 specificity by 41%. LFN-Acr/PA is the most potent known cell-permeable CRISPR-Cas inhibition system, significantly improving the utility of CRISPR for genome editing.
Increasing dengue outbreaks in temperate Brazil is linked toAedes aegyptiinvasion and infestation level driving widespread virus transmission
Authors: Bermann Thales , Gregianini Tatiana Schaffer , Godinho Fernanda Marques , Baethgen Ludmila Fiorenzano , Martiny Fernanda Letícia , Möllmann Erica Bortoli , Ruivo Amanda Pellenz , dos Santos Franciellen Machado , do Nascimento Ferreira Caroline , de Lima Gustavo Barbosa , Barbosa Danielly Alves Mendes , Dezordi Filipe Zimmer , Bauermann Milena , Selayaran Taina Machado , da Silva Loreto Elgion Lucio , Naveca Felipe Gomes , de Oliveira André Luiz Sá , da Veiga Ana Beatriz Gorini , Santos Paiva Marcelo Henrique , Campos de Lima Tulio , Bello Gonzalo , Bezerra Matheus Filgueira , de Oliveira Felipe Valter , Maciel-de-Freitas Rafael , Gräf Tiago , Salvato Richard Steiner , Wallau Gabriel Luz 
Published: February 2025

AbstractDengue fever, caused by the dengue virus (DENV), is the most important mosquito-borne disease impacting human health globally, it is particularly prevalent in tropical regions whereAedesvectors thrive. However, due to a recent expansion of the main dengue vectors to subtropical and temperate zones in the last decades there is an increasing human population at risk. Brazil is a global hotspot for dengue, accounting for 70% of all dengue cases reported worldwide in 2024. Noteworthy, dengue became endemic even in the southernmost Brazilian state of Rio Grande do Sul, which until recently had only imported cases. In this study, we integrated entomological, epidemiological, and high-resolution genomic data to investigate DENV transmission dynamics in Southern Brazil over nine years. From 2015 to 2023, we detected a partial to full invasion of the state municipalities byAedes aegypti, with dengue cases increasing substantially from 2020 onwards. The suitability index for transmission effectively predict the intensity of the outbreaks in the region, providing a two-month lead time before the surge in cases, representing an interesting proxy to forecast the outbreak size in the next few years. Invaded municipalities that surpassed a given case incidence level also increased, and by 2023, nearly half of the municipalities of the state surpassed that threshold, suggesting that dengue became endemic in the region. By analyzing 665 newly generated DENV genomes, we observed persistent overwintering lineages driving seasonal outbreaks, with the Northwest and Metropolitan regions serving as the main transmission hubs for dengue spread in the state. These regions were also the first to experience the endemic establishment of dengue lineages, making them key areas for targeted control efforts to mitigate further local outbreaks and the virus spread to other regions. These findings underscore the expansion of DENV-affected areas and increasing outbreaks into temperate zones, likely driven by the spread of the vector, associated with increased infestation level of the vector and widespread viral transmission in an immunologically naive population. In this context, enhanced control efforts are critical to mitigate the dengue burden in previously non-endemic areas.