bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemostat culturing reduces fecal eukaryotic virus load and delays diarrhea after virome transplantation
Authors: Offersen Simone Margaard , Adamberg Signe , Spiegelhauer Malene Roed , Mao Xiaotian , Rasmussen Torben Sølbeck , Larsen Frej , Zhong Jingren , Nguyen Duc Ninh , Nielsen Dennis Sandris , Aunsholt Lise , Thymann Thomas , Adamberg Kaarel , Brunse Anders 
Published: November 2024

AbstractFecal virome transfer (FVT) shows promise in reducing necrotizing enterocolitis (NEC), likely due to donor bacteriophages preventing the gut dysbiosis preceding disease. However, concurrent transfer of eukaryotic viruses may carry a risk of infection for the recipient. To increase safety, we investigated chemostat propagation as a method to eliminate eukaryotic viruses from donor feces while maintaining a diverse and reproducible bacteriophage community. Donor feces was collected from healthy suckling piglets and inoculated into a fermenter containing growth media supplemented with lactose and milk oligosaccharides (MOs). During continuous medium exchange (20% volume/h), dilution significantly reduced eukaryotic viruses. Viral richness was concurrently reduced although still preserving a stable community of 200-250 bacteriophages. Inclusion of MOs in the medium ensured higher bacterial richness and a bacterial community closer resembling donor feces. FecalLactobacillaceaebacteria were lost during cultivation but partially replaced by members of theBacteroidotaphylum in MO-supplemented cultures, accompanied by phages predicted to haveParabacteroidesas host. After cultivation, virus-like particles (VLPs) were isolated, and their ability to reduce NEC incidence testedin vivo. Preterm piglets were delivered by cesarean section and received either the lactose- or MO-propagated viromes by oral route (n= 14-15/group). These were compared with groups receiving the same dose of donor fecal virome (1010VLPs/kg) or vehicle control. The piglets were subsequently fed infant formula for 96 hours followed by euthanasia and tissue sampling. Both chemostat-propagated viromes effectively mitigated diarrhea compared to the donor virome. The donor virome partially engrafted in recipients and led to higher levels ofLactobacillaceaebacteria andLactobacillaceaetargeting phages. However, these signatures were lost in recipients of chemostat-propagated viromes, and only minor microbiome effects and no NEC prevention were observed. To conclude, we providein vivoproof-of-concept for chemostat propagation of fecal viruses as a means to deplete eukaryotic viruses and in turn reduce side effects in newborn virome recipients. However, chemostat culture conditions need further optimization to preserve the donor phageome.
Anillin tunes contractility and regulates barrier function during Rho flare-mediated tight junction remodeling
Authors: Craig Zie , Arnold Torey R. , Walworth Kelsey , Walkon Alexander , Miller Ann L. 
Published: November 2024

AbstractTo preserve barrier function, cell-cell junctions must dynamically remodel during cell shape changes. We have previously described a rapid tight junction repair pathway characterized by local, transient activation of RhoA, termed ‘Rho flares,’ which repair leaks in tight junctions via promoting local actomyosin-mediated junction remodeling. In this pathway, junction elongation is a mechanical trigger that initiates RhoA activation through an influx of intracellular calcium and recruitment of p115RhoGEF. However, mechanisms that tune the level of RhoA activation and Myosin II contractility during the process remain uncharacterized. Here, we show that the scaffolding protein Anillin localizes to Rho flares and regulates RhoA activity and actomyosin contraction at flares. Knocking down Anillin results in Rho flares with increased intensity but shorter duration. These changes in active RhoA dynamics weaken downstream F-actin and Myosin II accumulation at the site of Rho flares, resulting in decreased junction contraction. Consequently, tight junction breaks are not reinforced following Rho flares. We show that Anillin-driven RhoA regulation is necessary for successfully repairing tight junction leaks and protecting junctions from repeated barrier damage. Together, these results uncover a novel regulatory role for Anillin during tight junction repair and barrier function maintenance.Significance StatementBarrier function is critical for epithelial tissues. Epithelial cells maintain barrier function via tight junctions, which must be remodeled to allow for cell- and tissue-scale shape changes. How barrier function is maintained and remodeled as epithelial cells change shape remains unclear.The scaffolding protein Anillin is required for generating effective actomyosin contraction to reinforce damaged tight junctions; lack of reinforcement leads to repeated barrier leaks.These findings highlight a novel role for Anillin in tight junction remodeling and suggest that Anillin’s ability to tune the level and duration of local Rho activation affects the contractile output.
AI-directed voxel extraction and volume EM identify intrusions as sites of mitochondrial contact
Authors: Padman Benjamin S. , Lindblom Runa , Lazarou Michael 
Published: November 2024

ABSTRACTMembrane contact sites (MCS) establish organelle interactomes in cells to enable communication and exchange of materials. Volume electron microscopy (vEM) is ideally suited for MCS analyses, but semantic segmentation of large vEM datasets remains challenging. Recent adoption of artificial intelligence (AI) for segmentation has greatly enhanced our analysis capabilities. However, we show that organelle boundaries, which are important for defining MCS, are the least confident predictions made by AI. We outline a segmentation strategy termed AI-directed Voxel Extraction (AIVE), that combines AI predictions with image electron signals to confidently segment membrane boundaries irrespective of the AI model used. We demonstrate the precision conferred by AIVE by applying it to the quantitative analysis of organelle interactomes from multiple FIB-SEM datasets. Through AIVE, we discover a previously unknown category of mitochondrial contact that we term the mitochondrial intrusion. We hypothesise that intrusions serve as anchors that stabilize MCS and promote organelle communication.
ConvCGP: A Convolutional Neural Network to Predict Genotypic Values of Rice Traits from Compressed Genome-Wide Polymorphisms
Authors: Islam Tanzila , Hae Kim Chyon , Shimono Hiroyuki , Kimura Akio , Iwata Hiroyoshi 
Published: November 2024

AbstractThe growing size of genome-wide polymorphism data in animal and plant breeding has raised concerns regarding computational load and time, particularly when predicting genotypic values for target traits using genomic prediction. Although several deep learning and conventional methods, including dimensionality reduction techniques, such as principal component analysis (PCA) and autoencoders, have been proposed to address these challenges by selecting subsets of polymorphisms or compressing high-dimensional data for predictive analysis. However, these methods are often computationally intensive and time-consuming. A major challenge in applying high-dimensional genomic data directly to deep-learning models is the substantial computational cost and time required for hyperparameter tuning and model training. To address these limitations, we propose a novel deep learning approach that combines convolutional neural networks (CNNs) to predict the genotypic data of target traits with autoencoders to compress high-dimensional genome-wide polymorphism data. We tested this framework on high-dimensional rice datasets, focusing on agronomic trait prediction. By combining CNNs with autoencoders, our framework outperformed other machine-learning methods and recently proposed compression methods, demonstrating its potential to efficiently address the computational challenges associated with high-dimensional genomic data.
A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model ofMycobacterium ulceransinfection
Authors: Boakye-Appiah Justice Kofi , Tran Andy C. , Paul Matthew J. , Hart Peter , Phillips Richard O. , Harrison Thomas S. , Wansbrough-Jones Mark , Reljic Rajko 
Published: November 2024

AbstractBuruli ulcer (BU) disease, a neglected necrotizing tropical skin infection caused byMycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. Infections mostly occur in remote, rural areas of Central and West Africa, but also in Australia, Japan and Papua New Guinea. There is currently no vaccine against Buruli ulcer disease and all previous attempts using closely related bacteria and subunit proteins have been partially successful only.Here, we tested in mice a composite subunit formulation incorporating theMycobacterium ulceranstoxin mycolactone as the immunomodulator, and the antigens Ag85A and Polyketide Synthase Enzyme Ketoreductase A (KRA), formulated with Quil-A adjuvant (‘Burulivac’). Burulivac induced Ag85A and KRA antigen-specific antibodies, T cells and a mixed pro- and anti-inflammatory cytokine responses, which conferred absolute protection against Buruli ulcer disease in the mouse footpad model over a 14-week period of observation. This was superior to both live attenuated mycobacterial vaccines, that is, BCG and an avirulentM. ulceransstrain that lacks the mycolactone toxin (MuΔ). Interleukin 10 was found to be strongly associated with protection. We suggest that Burulivac is a promising vaccine candidate against Buruli ulcer disease that warrants further exploration.Author summaryBuruli ulcer is a neglected tropical disease caused by skin infections byMycobacterium ulcerans, an organism related to causative pathogens of tuberculosis and leprosy. The disease is endemic to parts of Central and West Africa but is also found in Australia, Japan and some other countries. While mortality is low, morbidity caused by extensive and unsightly ulceration of the skin is high. There currently is no vaccine against Buruli ulcer and all previous attempts to develop one have been unsuccessful.Here we developed a vaccine formulation termed ‘Burulivac’ that incorporates threeM. ulceransantigens, two of which are proteins and the third the mycolactone toxin, much responsible for the pathology of the BU disease. Our rationale was that in a vaccine setting and using a controlled dose of the toxin, we could calibrate the immune responses to selected antigens, so that they mimic those induced during natural infection. Using an experimental mouse footpad model of infection, we demonstrate that immunisation with Burulivac completely prevented ulceration in the mouse footpad over an extended 14-weeks period of observation, and that this correlated with elevated levels of anti-inflammatory cytokine Interleukin-10. We propose that Burulivac is a promising vaccine candidate that merits further testing and development.
Identification of transcriptome-wide cobalt chloride-induced hypoxia-responsive long noncoding RNAs regulated by cytoplasmic mRNA capping enzyme
Authors: Ghosh Pinaki , Islam Safirul , Mukherjee Chandrama 
Published: November 2024

AbstractLong non-coding RNAs (lncRNAs) are key regulators of gene expression in human cancers, influencing tumor microenvironment (TME). Hypoxia, a hallmark of solid tumors, elevates hypoxia-inducible factor 1α (HIF-1α), which regulates hypoxia-responsive lncRNAs (HRLs). These HRLs are essential in regulating gene expression under hypoxic conditions at both transcriptional and post-transcriptional levels. However, the mechanisms governing the post-transcriptional regulation of lncRNAs are not fully understood. It has been shown that the cytoplasmic pool of mRNA capping enzyme (cCE) can post-transcriptionally regulate its substrate uncapped mRNAs and lncRNAs in the cytoplasm, thereby preventing their degradation. Our previous study showed elevated expression of cCE under hypoxic conditions. This study aimed to determine whether cCE influences the transcriptome-wide HRLs in CoCl2-induced hypoxia in osteosarcoma U2OS cells. We identified 306 known lncRNAs with significant differential expression under hypoxic conditions, including 137 upregulated and 169 downregulated by RNA sequencing. Gene Ontology enrichment analysis revealed their distinct association with various cancers. Our investigation aimed to ascertain whether the cCE post-transcriptionally regulates these HRLs. Overexpression of a dominant negative form of cCE suggested cCE might post-transcriptionally regulate these HRLs. Future research should focus on understanding how cCE influences substrate HRLs, which play a crucial role in the bidirectional signaling circuit between TME and cancer cells under hypoxic stress as well as establishing cCE as a key factor that may alter cellular responses to hypoxia by stabilizing cCE-targeted lncRNAs.
Identifying spatially variable genes by projecting to morphologically relevant curves
Authors: Nicol Phillip B. , Ma Rong , Xu Rosalind J. , Moffitt Jeffrey R. , Irizarry Rafael A. 
Published: November 2024

AbstractSpatial transcriptomics enables high-resolution gene expression measurements while preserving the two-dimensional spatial organization of the sample. A common objective in spatial transcriptomics data analysis is to identify spatially variable genes within predefined cell types or regions within the tissue. However, these regions are often implicitly one-dimensional, making standard two-dimensional coordinate-based methods less effective as they overlook the underlying tissue organization. Here we introduce a methodology grounded in spectral graph theory to elucidate a one-dimensional curve that effectively approximates the spatial coordinates of the examined sample. This curve is then used to establish a new coordinate system that better reflects tissue morphology. We then develop a generalized additive model (GAM) to detect genes with variable expression in the newmorphologically relevantcoordinate system. Our approach directly models gene counts, thereby eliminating the need for normalization or transformations to satisfy normality assumptions. We demonstrate improved performance relative to current methods based on hypothesis testing, while also accurately estimating gene expression patterns and precisely identifying spatial loci where deviations from constant expression are observed. We validate our approach through extensive simulations and by analyzing experimental data from multiple platforms such as Slide-seq and MERFISH.
Spatial organization of mediated-macrophage chemoprotective niches in solid tumors: A mathematical analysis
Authors: Dangelser William , Stéphanou Angélique , Millet Arnaud 
Published: November 2024

AbstractAcquired resistance is one of the major causes of failure of standard therapies in cancer patients. Chemotherapeutic agents are still widely used and the understanding of the mechanisms leading to secondary resistance to these molecules are still puzzling. Recently, the role of the tumor immune microenvironment has been recognized. Among the cells potentially involved, macrophages seem to be the perfect culprits. In a previous work, we have shown that hypoxic macrophages are able to provide strong protection against 5-fluorouracil, a first-line chemotherapeutic agent in digestive cancers. In the present work, we use mathematical modeling to explore the spatiotemporal aspects of the treatment-induced organization of the tumor environment. Based on analytical and numerical analysis, we propose that macrophage-driven protection against chemotherapy under treatment does not rely solely on biochemical degradation, but is enhanced by the emergence of spatially structured chemotherapeutic protective niches. This work paves the way for the development of new therapeutic strategies that rely on targeting the spatial organization of tumors as a way to control treatment resistance.
Conserved moiety fluxomics
Authors: Fleming Ronan M.T. , Haraldsdottir Hulda S. , Preciat German , Huang Luojiao , Thiele Ines , Harms Amy , Hankemeier Thomas 
Published: November 2024

AbstractFluxomics seeks to infer reaction fluxes at genome-scale by introducing isotopically labelled metabolites into a living system and measuring the enrichment of isotopic tracers in downstream metabolites. This approach has the potential to quantify fluxes at genome-scale but current approaches to infer steady-state metabolic reaction fluxes are either not tractable or not efficient at genome-scale as the corresponding computational models are high-dimensional, involve nonlinear constraints and lack mathematical guarantees of convergence to a global optimum. Herein, we introduce conserved moiety fluxomics, which is a novel, efficient, mathematically transparent, and computationally efficient method to infer metabolic reaction flux at genome-scale. We demonstrate how identification of the set of conserved moieties for a given metabolic network leads to a novel moiety graph decomposition of a stoichiometric matrix that can be used to linearly relate metabolic reaction fluxes to the rate at which conserved moieties transition between metabolites. This linear formulation avoids combinatorial explosion because the number of conserved moieties is bounded, most reactions correspond to a small number of conserved moiety transitions, it is sufficient to represent the flow of moieties that have the potential to be labelled, and it is sufficient to represent constraints from those isotopologues that are actually measured. A non-linear yet strictly convex objective is used to ensure that inferred fluxes satisfy energy conservation and the second law of thermodynamics. Numerical results demonstrate the computational tractability of conserved moiety fluxomics at genome-scale, given liquid chromatography-mass spectrometry derived stationary mass isotopologue distribution data from an in vitro dopaminergic neuronal culture fed13Clabelled glucose. Conserved moiety fluxomics unites the strengths of constraint-based modelling and metabolic flux analysis and has the potential to be further enhanced to enable inference of fluxes in whole-body metabolic models, including from non-stationary isotopic labelling data.
Full quantum determination of the quasiequilibrium constant involved in the formation of ozone
Authors: Guillon G. , Honvault P. 
Published: November 2024

Forty years ago, measurements of enrichments in O18 in stratospheric ozone O3 revealed a value significantly greater than statistically expected and roughly equal in heavy isotopes O17 and O18. Despite numerous experimental and theoretical studies, this mass-independent fractionation (MIF) still remains unexplained. However, it is now accepted that its origin comes from isotopic effects found in the recombination reaction O+O2+M→O3 + M where M is a stabilizer, even if the theoretical origin of the isotope effects found in this reaction is still not known. Here we study the first of the two steps involved in this reaction, namely, the rapid quasiequilibrium O+O2 ⇌ O3* process where O3* is metastable ozone. The quasiequilibrium constant for this process is obtained from a full quantum dynamical approach. These high-level calculations yield the most accurate value of this quantity to date for O348 and O350. These reference results constitute a crucial stage for a better understanding of the ozone formation reaction, and could therefore help to unravel the mystery of MIF.

Published by the American Physical Society
2024
Understanding strategies employed by seniors in identifying deepfakes
Authors: Tang Zhong , Goh Dion Hoe-Lian , Lee Chei Sian , Yang Yihao 
Published: November 2024

PurposeThis paper aims to confront the rising threat of deepfake videos, focusing on the limited research on deepfake detection strategies among seniors. The study thus investigates seniors’ video credibility conceptualizations and identifies their deepfake detection strategies.Design/methodology/approachThis study employed semi-structured interviews with 20 seniors aged 55 to 70. Areas covered include their perceptions of video information credibility and identification strategies undertaken. Qualitative content analysis was conducted to interpret interview responses.FindingsSeniors emphasized the importance of objectivity, trustworthiness, believability, reliability and truthfulness in terms of video credibility. Regarding strategies for assessing video credibility, seniors employed five categories: character appearance, non-human visuals, audio, personal knowledge and external sources.Originality/valueThis study contributes to the literature on human-oriented deepfake detection strategies by uncovering diverse methods employed by seniors. It enhances the understanding of how individuals assess video credibility in the context of deepfakes. Furthermore, this study offers practical and applicable strategies for real-world deepfake detection.
How customers respond to chatbot anthropomorphism: the mediating roles of perceived humanness and perceived persuasiveness
Authors: Li Yang , Hou Ruolan , Tan Ran 
Published: November 2024

Purpose
This study aims to investigate how chatbots’ warmth and competence affect customer behavioural expectation (i.e. purchase, recommendation) through perceived humanness and perceived persuasiveness. Moreover, prior knowledge of chatbot is considered the boundary condition of the effects of chatbots’ warmth and competence.

Design/methodology/approach
A lab-in-field experiment with 213 participants and a scenario-based experiment of 186 participants were used to test the model using partial least squares structural equation modelling via SmartPLS 4.

Findings
Chatbot warmth positively affects customer behavioural expectation through perceived humanness while chatbot competence positively affects customer behavioural expectation through perceived persuasiveness. Prior knowledge of chatbot positively moderates the effect of chatbot warmth on perceived humanness.

Research limitations/implications
This study provides nuanced insights into the effects of chatbots’ warmth and competence on customer behavioural expectation. Future studies could extend the model by exploring additional boundary conditions of the effects of chatbots’ warmth and competence in different generations.

Practical implications
This study offers insightful suggestions for marketing managers on how to impress and convert online customers through designing verbal scripts in customer−chatbot conversations that encourage the customers to anthropomorphise the chatbots.

Originality/value
This study probes into the effects of chatbots’ warmth and competence on customer behavioural expectation by proposing and examining a novel research model that incorporates perceived humanness and perceived persuasiveness as the explanatory mechanisms and prior knowledge of chatbot as the boundary condition.