bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-dimensional tissue strain measurement using a row-column array during biaxial testing of excised ventricular myocardium
Authors: Navy Xavier , Sheng Zhiyu , Kim Kang , Cormack John M. 
Published: November 2024

AbstractObjectiveTo implement and validate a 3D volume imaging sequence and 3D strain estimation procedure for enhanced biaxial mechanical testing of excised ventricular myocardium.MethodsOne right- and one left-ventricular excised porcine myocardium specimens were tested using dual-loading protocol quasi-static biaxial mechanical testing. During biaxial testing, volume ultrasound images were acquired using a row-column addressed array probe using a synthetic aperture imaging sequence. Volume ultrasound images were used to compute tissue deformation using 3D correlation-based ultrasound speckle tracking. Ultrasound-derived tissue strains were validated against repeated measurements using typical standard optical camera imaging of the surface deformation of the specimen.ResultsSynthetic aperture imaging with the RCA yielded artifact-free and uniform ultrasound speckle for high-fidely speckle tracking of tissue deformation. Ultrasound-derived tissue strain is in good agreement with ground-truth camera-derived surface strain measurements (root-mean-square error is 1.6% strain).ConclusionHigh-fidelity 3D strain measurement with ultrasound imaging is accurate and can enhance biomechanical insights from biaxial experimentation, especially in large tissues such as porcine and human myocardium where assumptions of plane stress and incompressibility may not apply.
Reconstitution of SPO11-dependent double-strand break formation
Authors: Zheng Zhi , Zheng Lyuqin , Arter Meret , Liu Kaixian , Yamada Shintaro , Ontoso David , Kim Soonjoung , Keeney Scott 
Published: November 2024

AbstractHomologous meiotic recombination starts with DNA double-strand breaks (DSBs) generated by SPO11 protein1. SPO11 is critical for meiosis in most species but the DSBs it makes are also dangerous because of their mutagenic2and gametocidal3potential, so cells must foster SPO11’s beneficial functions while minimizing its risks4. SPO11 mechanism and regulation remain poorly understood. Here we report reconstitution of DNA cleavage in vitro with purified recombinant mouse SPO11 bound to its essential partner TOP6BL. Similar to their yeast orthologs5,6, SPO11– TOP6BL complexes are monomeric (1:1) in solution and bind tightly to DNA. Unlike in yeast, however, dimeric (2:2) assemblies of mouse SPO11–TOP6BL cleave DNA to form covalent 5′ attachments requiring SPO11 active site residues, divalent metal ions, and SPO11 dimerization. Surprisingly, SPO11 can also manifest topoisomerase activity by relaxing supercoils and resealing DNA that it has nicked. Structure modeling with AlphaFold37illuminates the protein-DNA interface and suggests that DNA is bent prior to cleavage. Deep sequencing of in vitro cleavage products reveals a rotationally symmetric base composition bias that partially explains DSB site preferences in vivo. Cleavage is inefficient on complex DNA substrates, partly because SPO11 is readily trapped in DSB-incompetent (presumably monomeric) binding states that exchange slowly. However, cleavage is improved by using substrates that favor DSB-competent dimer assembly, or by fusing SPO11 to an artificial dimerization module. Our results inform a model in which intrinsically feeble dimerization restrains SPO11 activity in vivo, making it exquisitely dependent on accessory proteins that focus and control DSB formation so that it happens only at the right time and the right places.
TIRE-seq: an Integrated Sample Extraction and Transcriptomics Workflow for High Throughput Perturbation Studies
Authors: O’Keeffe Piper , Nouri Yasmin , Saw Hui Shi , Moore Zachery , Baldwin Tracey M. , Olechnowicz Sam W.Z. , Jabbari Jafar S. , Squire David McG , Leslie Stephen , Wang Changqing , You Yupei , Ritchie Matthew E. , Cross Ryan S. , Jenkins Misty R. , Audiger Cindy , Naik Shalin H. , Whittle James R. , Freytag Saskia , Best Sarah A. , Hickey Peter F. , Amann-Zalcenstein Daniela , Bowden Rory , Brown Daniel V. 
Published: November 2024

AbstractRNA sequencing (RNA-seq) is widely used in biomedical research, advancing our understanding of gene expression across biological systems. Traditional methods require upstream RNA extraction from biological inputs, adding time and expense to workflows. We developed TIRE-seq (Turbocapture Integrated RNA Expression Sequencing) to address these challenges. TIRE-seq integrates mRNA purification directly into library preparation, eliminating the need for a separate extraction step. This streamlined approach reduces turnaround time, minimizes sample loss, and improves data quality. A comparative study with the widely used Prime-seq protocol demonstrates TIRE-seq’s superior sequencing efficiency with crude cell lysates as inputs. TIRE-seq’s utility was demonstrated across three biological applications. It captured transcriptional changes in stimulated human T cells, revealing activation-associated gene expression profiles. It also identified key genes driving murine dendritic cell differentiation, providing insights into lineage commitment. Lastly, TIRE-seq analyzed the dose-response and time-course effects of temozolomide on patient-derived neurospheres, identifying differentially expressed genes and enriched pathways linked to the drug’s mechanism of action. With its simplified workflow and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies across diverse biological systems.
Cardiac electrical abnormalities in a mouse model of left ventricular non-compaction cardiomyopathy
Authors: Fernandes Vítor S. , Caballero Ricardo , Siguero-Álvarez Marcos , Papoutsi Tania , Gimeno Juan Ramón , Delpón Eva , de la Pompa José Luís 
Published: November 2024

AbstractMutations inMINDBOMB 1(MIB1), encoding an E3 ubiquitin ligase of the NOTCH signaling pathway, cause left ventricular noncompaction cardiomyopathy (LVNC) in mice and humans, increasing the risk of arrhythmia and left ventricular dysfunction. This study aimed to investigate the effect ofMIB1mutations on cardiac electrical activity. We examined maleMib1flox;Tnnt2Cremice, a disease model of LVNC, and wildtype littermates on the C57BL/6J genetic background. Our results demonstrate that the gap-junction protein connexin43 was delocalized from the intercalated disks to the lateral long axis ofMib1flox;Tnnt2Crecardiomyocytes. Cardiomyocyte electrophysiology revealed an increase in the Na (INa) peak density at potentials between –50 and –30 mV inMib1flox;Tnnt2Cremice, with no changes in INaactivation or inactivation kinetics.Mib1flox;Tnnt2Crecardiomyocytes also showed decreases in outward K+peak currents and currents at the end of depolarizing pulses at potentials ≥−10 mV and ≥−20 mV, respectively, and this was accompanied by a lower charge density at ≥−20 mV. Action potential duration was increased inMib1flox;Tnnt2Crecardiomyocytes. The cardiac stress, induced by swimming endurance training or β-adrenergic stimulation with isoproterenol, increases QTc duration inMib1flox;Tnnt2Cremice, accompanied by a decrease in T-wave amplitude and area. Swimming endurance training decreased heart rate in wildtype andMib1flox;Tnnt2Cremice but was unaffected by long-term isoproterenol treatment. These mouse findings are in agreement with an increased QTc duration found in LVNC patients carryingMIB1mutations. These results provide insight into the outcomes of LVNC and relate its pathogenicity to impaired ventricular repolarization.
TaxSEA: an R package for rapid interpretation of differential abundance analysis output
Authors: Ryan Feargal J. 
Published: November 2024

AbstractMicrobial communities are essential regulators of ecosystem function, with their composition commonly assessed through DNA sequencing. Most current tools focus on detecting changes among individual taxa (e.g., species or genera), however in other omics fields, such as transcriptomics, enrichment analyses like Gene Set Enrichment Analysis (GSEA) are commonly used to uncover patterns not seen with individual features. Here, we introduce TaxSEA, an R package for taxon set enrichment analysis. TaxSEA integrates taxon sets from five public microbiota databases (BugSigDB, MiMeDB, GutMGene, mBodyMap, and GMRepoV2) to assess whether disease signatures, metabolite producers, or previously reported associations are enriched or depleted in a metagenomic dataset of interest. In-silico assessments show TaxSEA is accurate across a range of set sizes. When applied to differential abundance analysis output from Inflammatory Bowel Disease and Type 2 Diabetes metagenomic data, TaxSEA outperforms current tools and can rapidly identify changes in functional groups corresponding to known associations. We also show that TaxSEA is robust to the choice of differential abundance (DA) analysis package. In summary, TaxSEA enables researchers to efficiently contextualize their findings within the broader microbiome literature, facilitating rapid interpretation and advancing understanding of microbiome–host and environmental interactions.
CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation during cellular differentiation
Authors: Karpinska Magdalena A. , Zhu Yi , Ghazvini Zahra Fakhraei , Ramasamy Shyam , Barbieri Mariano , Cao T. B. Ngoc , Varahram Natalie , Aljahani Abrar , Lidschreiber Michael , Papantonis Argyris , Oudelaar A. Marieke 
Published: November 2024

ABSTRACTEnhancers and promoters interact in 3D chromatin structures to regulate gene expression. Here, we characterize the mechanisms that drive the formation of these structures and their function in gene regulation in a lymphoid-to-myeloid transdifferentiation system. Based on analyses at base-pair resolution, we demonstrate a close correlation between binding of regulatory proteins, formation of chromatin interactions, and gene expression. Integration of multi-way interaction analyses and computational modeling shows that tissue-specific gene loci are organized into chromatin hubs, characterized by cooperative interactions between multiple enhancers, promoters, and CTCF-binding sites. Depletion of CTCF strongly impairs the formation of these structures. However, the effects of CTCF depletion on gene expression are modest and can be explained by rewired enhancer-promoter interactions. This demonstrates an instructive role for enhancer-promoter interactions in gene regulation that is independent of cooperative interactions in chromatin hubs. Together, these results contribute to a mechanistic understanding of the structure-function relationship of the genome during cellular differentiation.
Mobilisation of data from natural history collections can increase the quality and coverage of biodiversity information
Authors: Blades Bryony , Ronquillo Cristina , Hortal Joaquín 
Published: November 2024

AbstractAimQuantify potential gains to insect data on the Global Biodiversity Information Facility (GBIF) through further digitisation of natural history collections, assess to what degree this would fill biases in spatial and environmental record coverage, and deepen understanding of environmental bias with regard to climate rarity.LocationAfrotropical realm (mainland only)Time period1814-2022Major taxa studiedCatharsiusHope, 1837 (Coleoptera: Scarabaeidae)MethodsWe compared inventory completeness of AfrotropicalCatharsiusGBIF data to a dataset which combined these with records from a recent taxonomic revision. We analysed how this improved dataset reduced regional and environmental bias in the distribution of occurrence records using an approach that identifies well-surveyed spatial units of 100×100km as well as emerging techniques to classify rarity of climates.ResultsThe number of cells for which inventory completeness could be calculated, as well as coverage of climate types by “well-sampled” cells, increased three-fold when using the combined set compared to the GBIF set. Improvements to sampling in Central and Western Africa were particularly striking. Coverage of rare climates was similarly improved, as not a single well-sampled cell from the GBIF data alone occurred in the rarest climate types. Inclusion of further records from natural history collections increased the total number of occurrences, but also filled persisting spatial and environmental data gaps on GBIF.Main conclusionsThese findings support existing literature that suggests data gaps on GBIF are still pervasive, especially for insects and in the tropics and, so, is not yet ready to serve as a standalone data source for all taxa. Biases in spatial coverage of records translate to uneven sampling of environmental conditions, hindering our ability to describe the full breadth of species’ niches, especially so in climates that occur infrequently. However, we show that natural history collections hold the necessary information to fill many of these gaps, and their further digitisation should be a priority.
A novelArabidopsis thalianaprotein, ABAP1 INTERACTING PROTEIN 10, mediates crosstalk between the cell cycle and primary metabolism
Authors: Montessoro Patrícia , Paixão Joaquin Felipe Roca , Costa Carinne N M , Ducatti Laura , Grangeiro Letícia P Perdigão , Fusaro Adriana Flores , Ballesteros Helkin F , Iurif Vanessa , Cabral Luiz Mors , de Andrade Jelmir Craveiro , Tessaro Leticia , de Paula Bernardo Wallace , Coelho Fernanda Silva , de Almeida-Engler Janice , Campostrini Eliemar , Conte-Junior Carlos Adam , Hemerly Adriana Silva 
Published: November 2024

AbstractPlants have developed a sophisticated regulatory network that coordinates gene expression in meristematic zones in response to environmental conditions. Here, we identified a protein in Arabidopsis (Arabidopsis thaliana) that interacts with Armadillo BTB Arabidopsis protein 1 (ABAP1), a negative regulator of the cell cycle in plants. We characterized ABAP1 Interacting Protein (named AIP10) investigating its role in modulating plant development. T-DNA insertion lines with silenced expression ofAIP10were evaluated phenotypically (morphology, fresh and dry weight), via transcriptomics analyses (RNA-seq and RT-qPCR), physiologically (biochemically, Fluorcam and Li- COR), and metabolically (ATR-FTIR). We showed that AIP10 integrates cell division rates with transcriptional and primary metabolism reprogramming, through its protein interactions with ABAP1 and KIN10, a subunit of SnRK1 (Sucrose non-fermenting-1- related protein kinase 1). ABAP1 levels and activity were reduced in the absence of AIP10, licensing cell cycle progression for longer periods, which culminated in increased rates of cell division that boosted vegetative and reproductive growth.AIP10silencing triggered a major transcriptional reprogramming of plant primary metabolism, possibly through SnRK1 regulation.aip10mutants showed increased photosynthetic efficiency, as well as boosted carbon fixation, leading to increased biomass, seed productivity, and higher contents of proteins, lipids (triglycerides), and carbohydrates. Finally, we propose that the modulation ofAIP10expression is part of a mechanism that coordinates higher rates of cell division with better photosynthetic performance and carbon fixation to metabolically meet the plant energy demand, allowing the generation of plants with increased biomass and productivity.One-sentence summaryABAP1 INTERACTING PROTEIN10 connects the cell cycle and plant metabolism, with its silencing leading to increased cell division, carbon fixation, and metabolite levels in Arabidopsis.
Measuring flicker induced vasodilation at a high spatial and temporal resolution in the human retina
Authors: Senée Pierre , Krafft Léa , Loukili Inès , Farias Daniela Castro , Thouvenin Olivier , Atlan Michael , Paques Michel , Meimon Serge , Mecê Pedro 
Published: November 2024

AbstractNeurovascular coupling (NVC) is a crucial process in which blood flow is dynamically adjusted to meet the metabolic demands of active neurons. In this study, we introduce an innovative method forin-vivoimaging of retinal blood vessel dilation in response to visible light stimulation, offering insights into the functional regulation of retinal blood flow. Using high-resolution, high-speed phase contrast imaging, we continuously monitored retinal vessel dynamics in eight healthy subjects, capturing precise temporal and spatial changes in vessel size under both stimulated and baseline conditions. We have measured a significant vessel dilation of 5.2% ± 1.6% (4.4 µm ± 1.3 µm) during flicker-stimulation compared to a dilation of 2.5% ± 1% (2.1 µm ± 0.9 µm) without stimulation. The flexibility of our method also allowed for the exploration of various acquisition and stimulation settings, broadening possibilities for investigating neurovascular coupling in the retina. This work not only enhances our understanding of neurovascular coupling but also has the potential to identify new biomarkers for vision-impairing conditions and neurodegenerative diseases.SignificanceNeurovascular coupling is a fundamental mechanism of the brain which locally regulates blood flow in response to changes in neuronal activity. Here, we present a new imaging technique that enables measuring vasodilation in response to visible light stimulation of the neurons at high spatial and temporal resolution in the living human retina. Owing to the unprecedented measurement precision of the presented technique, we provide new insights into the inner working of functional blood flow regulation in the retina. Clinically, this method holds promise for vascular dysfunction early detection, which can improve diagnosis of retinal and neurodegenerative diseases, as well as assist the development of new targeted therapies.
Evaluation of protein intake and protein quality in New Zealand vegans
Authors: Soh Bi Xue Patricia , Vignes Matthieu , Smith Nick W. , von Hurst Pamela R , McNabb Warren C. 
Published: November 2024

AbstractDietary protein provides indispensable amino acids (IAAs) that the body cannot synthesise. Past assessments of total protein intake from vegan populations in western, developed countries were found to be low but not necessarily below daily requirements. However, plant-sourced proteins generally have lower quantities of digestible IAAs as compared to animal-sourced proteins. Simply accounting for protein intake without considering AA profile and digestibility could overestimate protein adequacy among vegans. This study quantified protein intake and quality, as compared to reference intake values among 193 NZ vegans using a four-day food diary. Protein and IAA composition of all foods were derived from New Zealand FoodFiles and the United States Department of Agriculture and adjusted for True Ileal Digestibility (TID). Mean protein intakes for males and females were 0.99 and 0.81 g/kg /day, respectively with 78.8% of males and 74.5% of females meeting the Estimated Average Requirement for protein. Plant-sourced proteins provided 52.9 mg of leucine and 35.7 mg of lysine per gram of protein and were below the reference scoring patterns (leucine: 59mg/g, lysine: 45mg/g). When adjusted to individual body weight, average IAA intakes were above daily requirements, but lysine just met requirements at 31.2 mg/kg of body weight/day (reference: 30 mg/kg/day). Upon TID adjustment, the percentage of vegans meeting adequacy for protein and IAA decreased and only approximately 50% of the cohort could meet lysine and leucine requirements. Hence, lysine and leucine were the most limiting IAAs in the vegan cohort’s diet. Legumes and pulses contributed most to overall protein and lysine intake. An increased proportion of legumes and pulses can potentially increase these intakes but must be considered in the context of the whole diet. AA composition and digestibility are important aspects of protein quality when assessing protein adequacy and is of particular importance in restrictive diets.
Consumption of Ciprofloxacin as the sole Carbon and energy source and Phenomenal Transformation to a Culturable nanometer-sized-bacterium demonstrated by a hospital-waste-water isolateKlebsiellasp. SG01
Authors: Ganguli Sriradha , Chakraborty Ranadhir 
Published: November 2024

AbstractAntimicrobial resistance is a global crisis. Biodegradation by bacteria is an effective strategy to remove the micropollutant from the environment. In this study, we demonstrate that a persistent fluoroquinolone, ciprofloxacin (CIP) can be degraded by a multidrug-resistantKlebsiellasp. SG01 and used as its only carbon source. The degradation was quantified using UV-vis spectroscopy and the degraded product was less toxic than the parent compound as tested against a susceptibleEscherichia coliK12. SG01 changes into nano-sized cells as culturable nanobacterium, passes through a 0.22 μm pore-size filter while growing on ciprofloxacin, and shows a shorter generation time than cells grown on glucose or rich medium. The basis for the changed growth phenotype of nano-SG01 cells and metabolic changes was partially established by the whole-genome transcriptome.ImportanceFluoroquinolones (FQs) constitute a class of persistent antimicrobials, having a high affinity for sludge, sediments, and soil with reported half-lives of 10.6 days in surface waters and up to 580 days in soil matrices. However, more than 50% consumption or degradation of CIP at higher concentration (∼2g/L) within 48 hours is not yet reported. Also, the isolate transforms into a nano-form to consume the antibiotic and economizes its metabolism to degrade CIP. From the One Health Approach perspective, nanobacterial transformation is an alarming concern as such viable nanobacteria continue to proliferate and may trigger infection in host. The strategy should be to utilize this powerful strain for the biodegradation of CIP.
Calcineurin inhibition deactivates pyruvate dehydrogenase and induces proximal tubule cell metabolic dysfunction, causing profibrotic phenotype
Authors: Oda Yasuhiro , Nishi Hiroshi , Hamano Fumie , Yoshida Teruhiko , Kita Yoshihiro , Kopp Jeffrey B. , Nangaku Masaomi 
Published: November 2024

ABSTRACTCalcineurin inhibitors (CNIs) are indispensable immunosuppressants for transplant recipients and patients with autoimmune diseases, but chronic use causes nephrotoxicity, including kidney fibrosis. Why inhibiting calcineurin, a serine/threonine phosphatase, causes kidney fibrosis remains unknown. We performed single-nucleus RNA sequencing of the kidney from a chronic CNI nephrotoxicity mouse model and found an increased proportion of injured proximal tubule cells, which exhibited altered expression of genes associated with oxidative phosphorylation, cellular senescence and fibrosis. In cultured primary human renal proximal tubule epithelial cells, CNIs caused phosphorylation (deactivation) of pyruvate dehydrogenase, impaired mitochondrial metabolism and senescence-associated phenotypes, all of which were ameliorated by pyruvate dehydrogenase activation. Finally, administration of dichloroacetic acid, a known activator of pyruvate dehydrogenase, in the chronic CNI nephrotoxicity mouse model mitigated kidney fibrosis and the associated transcriptional changes. Collectively, calcineurin inhibition deactivates pyruvate dehydrogenase and induces proximal tubule cell metabolic dysfunction, causing profibrotic phenotype.