bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA-guided CRISPR/Cas12 for RNA targeting
Authors: Orosco Carlos , Rananaware Santosh R. , Huang Boyu , Hanna Michael P. , Ahmadimashhadi M. Reza , Lewis Jordan G. , Baugh Michael P. , Bodin August P. , Flannery Sarah J. , Lange Ian H. , Fang Zoe R. , Karalkar Vedant N. , Meister Katelyn S. , Jain Piyush K. 
Published: November 2024

AbstractCRISPR-Cas nucleases are transforming genome editing, RNA editing, and diagnostics but have been limited to RNA-guided systems. We present ΨDNA, a DNA-based guide for Cas12 enzymes, engineered for specific and efficient RNA targeting. ΨDNA mimics a crRNA but with a reverse orientation, enabling stable Cas12-RNA assembly and activating trans-cleavage without RNA components. ΨDNAs are effective in sensing short and long RNAs and demonstrated 100% accuracy for detecting HCV RNA in clinical samples. We discovered that ΨDNAs can guide certain Cas12 enzymes for RNA targeting in cells, enhancing mRNA degradation via ribosome stalling and enabling multiplex knockdown of multiple RNA transcripts. This study establishes ΨDNA as a robust alternative to RNA guides, augmenting the potential of CRISPR-Cas12 for diagnostic applications and targeted RNA modulation in cellular environments.
Validation of the PETS-stroke-A patient reported measure (PRM) of treatment burden after stroke
Authors: Taylor-Rowan Martin , Eton David T , McLeod Hamish J. , Rizeq Jala , Kidd Lisa , Currie Grace , Quinn Terry J , Mair Frances S , Gallacher Katie I 
Published: November 2024

AbstractIntroductionTreatment burden is the workload of healthcare for people with long-term conditions and the impact on wellbeing. A validated measure of treatment burden for use as an outcome measure in stroke trials is needed. We adapted a patient-reported measure (PRM) of treatment burden in multimorbidity, PETS (Patient Experience with Treatment and Self-Management version 2.0), to create a stroke-specific measure, PETS-stroke, and examined its psychometric properties.Patients and MethodsWe recruited stroke and transient ischaemic attack (TIA) survivors between Feb 2022-June 2023 from 10 hospitals in the UK and through the Scottish Health Research Register (SHARE). Participants completed the PETS-stroke questionnaire along with 3 other PRM’s (Stroke Southampton Self-Management Questionnaire, The Satisfaction with Stroke Care Measure, The Shortened Stroke Impact Scale). We performed confirmatory factor analysis to test the factor structure of the PETS-stroke. We assessed Spearman’s rank correlations between PETS-stroke and other PRMs to determine convergent validity. Intra-class coefficient was performed to assess test-retest reliability. Proportions of missing data along with feedback from qualitative interviews were used to determine feasibility. T-tests were conducted to examine variations in PETS-stroke scores based on multimorbidity and socioeconomic factors.ResultsThree-hundred-eighty-one participants were included. The best fit was achieved with a 9-factor structure and internal consistency was good (Omega values 0.729 to 0.921). The factor loadings for the individual indicator items across eight of the nine domains were moderate to strong. All domains of PETS-stroke showed moderate to strong correlations with at least one other PRM. Test-retest reliability was good for all domains (ICC>0.7). Qualitative feedback on feasibility was positive and missing data was within acceptable limits for 7 domains. PETS-stroke scores significantly differed based on multimorbidity in 3 domains and in 8 domains based on socioeconomic status.DiscussionPsychometric performance suggests PETS-stroke is a highly promising measure of treatment burden after stroke.
Poxviruses induce a nuclear environment in the cytoplasm to promote viral replication
Authors: Veratti Pia , Wyler Emanuel , Read Clarissa , Scherer Myriam , Tan Jiang , Walther Paul , Wider Stephanie , Weidl Daniel , Full Florian 
Published: November 2024

AbstractThe family Orthopoxviridae comprises several members that can cause disease in humans, including Small-, Cow-, Camel-, and Monkeypoxvirus. In 2022 a global outbreak of the zoonotic monkeypoxvirus started with human- to- human transmission and more than 100 000 global cases in all continents. This outbreak emphasizes the need for more basic research to get a better understanding of poxvirus biology.We characterized the cellular response to poxvirus infection and performed bulk RNA-sequencing of primary human fibroblasts infected with Modified-Vaccinia Ankara Virus (MVA), Vaccinia Virus, Cowpoxvirus, Camelpoxvirus and 4 different Monkeypoxvirus isolates (clade 1-2b) at various time points to compare the transcriptome of infected cells. We could demonstrate that MVA infection leads to a potent activation of innate immune genes that is absent in other samples. Camelpoxvirus infection results in a strong activation of NF-kB signaling 2h post infection whereas all other viruses inhibit NF-kB activation. In addition, we observed transport of cellular proteins like histone H1, lamin A/C, emerin and topoisomerase II A/B from the nucleus into cytoplasmic poxvirus factories. This correlates with drastic structural changes inside the nucleus in electron microscopy, namely formation of nuclear filaments, indicating intensive remodeling of the nuclear architecture. Accordingly, inhibition of topoisomerase using the clinically approved topoisomerase inhibitor epirubicin reduced viral replication of several Mpox strains. We observe a reduction of viral replication by epirubicin in cells of human and mouse species, indicating that the recruitment of TOP2B into viral factories is crucial for MPXV replication.
Genomes of two invasiveAdelgesspecies (hemlock woolly adelgid and pineapple gall adelgid)enable characterization of nicotinic acetylcholine receptors
Authors: Glendening AM , Stephens C , Vuruputoor VS , Stern DL , Hogenhout SA , Mathers TC , Chaganti T , Pauloski N , Cernak TA , Wegrzyn JL , Fetter KC 
Published: November 2024

AbstractTwo invasive hemipteran adelgids cause widespread damage to North American conifers.Adelges tsugae(the hemlock woolly adelgid) has decimatedTsuga canadensisandTsuga caroliniana(the Eastern and Carolina hemlocks, respectively).A. tsugaewas introduced from East Asia and reproduces parthenogenetically in North America, where it can kill trees rapidly.A. abietis,introduced from Europe, makes “pineapple” galls on several North American spruce species, and weakens trees, increasing their susceptibility to other stresses. Broad-spectrum insecticides that are often used to control adelgid populations can have off-target impacts on beneficial insects and the development of more selective chemical treatments could improve control methods and minimize ecological damage. Whole genome sequencing was performed on both species to aid in development of targeted pest control solutions and improve species conservation. The assembledA. tsugaeandA. abietisgenomes are 220.75 Mbp and 253.16 Mbp, respectively, each consisting of nine chromosomes and both genomes are over 96% complete based on BUSCO assessment. Genome annotation identified 11,424 and 14,118 protein-coding genes inA. tsugae and A. abietis, respectively. Comparative analysis across 29 Hemipteran species and 14 arthropod outgroups identified 31,666 putative gene families. Gene family expansions inA. abietisincluded ABC transporters and carboxypeptidases involved in carbohydrate metabolism, while both species showed contractions in core histone families and oxidoreductase pathways. Gene family expansions inA. tsugaehighlighted families associated with the regulation of cell differentiation and development (survival motor protein, SMN;juvenile hormone acid methyltransferaseJHAMT) as well as those that may be involved in the suppression of plant immunity (clip domain serine protease-D, CLIPD;Endoplasmic reticulum aminopeptidase 1, ERAP1). Among the analyzed gene families, Nicotinic acetylcholine receptors (nAChRs) maintained consistent copy numbers and structural features across species, a finding particularly relevant given their role as targets for current forestry management insecticides. Detailed phylogenetic analysis of nAChR subunits across adelgids and other ecologically important insects revealed remarkable conservation in both sequence composition and predicted structural features, providing crucial insights for the development of more selective pest control strategies.
Population regulation in semelparous deep-sea squid is driven by ecological conditions in surface waters and whale predation at depth
Authors: Rademaker Mark , ten Brink Hanna , Hoving Henk-Jan , Visser Fleur , van Leeuwen Anieke 
Published: November 2024

AbstractPredator-prey interactions present a powerful framework for understanding population regulation in natural systems, including the vast and understudied pelagic deep sea. Oceanic squid are among the most abundant and important species groups in this habitat and function as primary prey for the largest marine top predators, deep-diving cetaceans. At the same time, these cryptic animals are highly data deficient. Insight into the dynamics of deep-sea squid populations and the impacts of predation by top-predators is crucial for designing conservation strategies and developing a general theory of deep-sea ecology. Here, we offer fundamental new insights into how individual life history and predation interact to shape population regulation in deep-sea squid. Using empirical data, we develop a size-structured population model for a highly abundant histioteuthid deep-sea squid. We show that population regulation is driven primarily by conditions experienced as paralarvae in the upper water column, where they face intense resource competition. Relaxation of this competition following ontogenetic migration as juveniles drives exponential-like growth curves. Population dynamics exhibit single-cohort cycles, producing regular ‘seasonal’ patterns in reproduction, even in the absence of any environmental seasonality. Furthermore, we demonstrate that predation by deep-diving cetaceans at different depths can lead to emergent facilitation between top predators. This reveals the complex interdependencies in trophic networks connecting the deep sea with surface waters. Our findings provide critical insights into the ecological functioning of the pelagic deep-sea and their link with surface waters. These insights are urgently needed to better understand and conserve this vast, data-deficient habitat, which endangered deep-diving predators depend on but is under major stress from anthropogenic activities.
Pathway Volcano: An interactive tool for pathway guided visualization of differential expression data
Authors: OConnell Thomas M 
Published: November 2024

AbstractSummaryThe increasing size and complexity of omics datasets can make effective visualization and interpretation very challenging. Differential expression datasets as from RNA-sequencing and proteomics can contain many thousands of features and even after filtering for significance there can be hundreds or thousands of features to consider. A common tool for visualizing this type of data is the volcano plot where each feature is plotted as log2 transformed fold change along the x-axis and the negative log10 of a p-value along the y-axis. These plots provide a useful visualization of the largest and most significant changes, but the majority of the features are often crowded and overlapping near the “cone” of the volcano. In order to provide a biologically informative way to simplify the visualization and interpretation of these types of datasets we developed the Pathway Volcano tool. This R-Shiny based software utilizes the Reactome API to select specific pathways and then filters the volcano plots to show only the data associated with those pathways. In this manner, many of the significant features in the crowded section of the volcano plot can be revealed to support the impact of specified pathways. This tool provides a range of interactive features to interrogate the data along with the ability to download png files and tables with pathway associated data.Availability and implementationPathway Volcano is a freely available R Shiny package. The program was developed in R version 4.3.3 using R Studio version 2024.09.1 Build 394. Running the app locally requires the packages ggplot2 (1), plotly (2), shiny (3) dplyr (4) and ReactomeContentServer (5). The full code and documentation including example datasets are available athttps://github.com/thoconne/PathwayVolcanoContactthoconne@iu.edu
Sex-dependent effects of a glutamine supplementation on metabolic disorders, intestinal barrier function and gut microbiota in mice with diet-induced obesity
Authors: Lefebvre Candice , Tiffay Adam , Breemeersch Charles-Edward , Dreux Virginie , Bôle-Feysot Christine , Guérin Charlène , Breton Jonathan , Maximin Elise , Monnoye Magali , Déchelotte Pierre , Douard Véronique , Coëffier Moïse , Goichon Alexis 
Published: November 2024

AbstractRationaleObesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. Glutamine (Gln) supplementation previously showed beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize in mice the sex-dependent effects of a Gln supplementation during high fat diet induced obesity.MethodsMale and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). From W12, mice received or not Gln in drinking water (2g/kg/day; n=12/group). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota and inflammatory/endocrine adipose response have been assessed. Data were analyzed usingt-test or Mann-Whitney test (HFD effect), and two-way ANOVA (HFD x Gln) followed by Bonferroni post-tests.ResultsIn both male and female mice, Gln supplementation failed to improve body weight and body composition. However, Gln reduced glucose intolerance in HFD males (AUC reduced by 14.57%, p<0.05) that was associated to a partial restoration of plasma resistin and insulin and to a trend for a limitation of adipose inflammatory response. In males, Gln did not affect gut microbiota composition and colonic response. To the opposite, in females fed HFD, Gln supplementation led to gut microbiota changes (increase ofBacteroidotaandPseudomonadotaphyla; increase ofMuribaculaceaeandTannerellaceaefamilies), increased colonic inflammatory markers (TNFα, IL-1β, TLR4, Myd88, Irf3) that were associated to increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR.ConclusionsHigh fat diet mice exhibit sex-dependent response to glutamine supplementation with protective effects in males and harmful effects in females. The role of gut microbiota should be deeply deciphered in further investigations.
The Impact of Excessive Muscle Co-contraction on Sit-to-Stand Performance in High-Heeled Footwear
Authors: Naik Ganesh R. , Pujari Amit N. 
Published: November 2024

AbstractThis study aimed to analyse the effects of co-contraction on quadriceps and hamstring muscles during sit-to-stand tasks for females wearing shoes with different heel heights. The study aimed to identify compensatory strategies during sit to stand task in response to excessive muscle co-contraction during high heeled gait. Sixteen healthy young women (age: 24.4±1.7 years, body mass index: 18.4±1kg/m2, weight: 50.2±5.2kg, height: 1.63±4.4m) participated in this study. Electromyography signals were recorded from three quadriceps (vastus medialis, vastus lateralis, and rectus femoris) and one hamstring (semitendinosus) muscles. The participants wore shoes with different heights, including 4cm, 6cm, 8cm, and 10cm. For each heel height, we computed co-contraction index to measure postural balance using quadriceps to hamstring muscle pairs. The results that were obtained and quantified with statistical measures show that for elevated shoes if co-contraction increases, both quadriceps and hamstring muscles tend to compensate. This suggests that the capacity of quadriceps and hamstring muscles to compensate is essential to retain normal walking and sit-to-stand (STS) tasks in co-contracted persons. However, the compensation mechanisms may induce imbalance, muscle stiffness, and fatigue for women who regularly use high-heeled shoes during sit-to-stand tasks.
SFPQ-TFE3gene fusion reciprocally regulates mTORC1 activity and induces lineage plasticity in a novel mouse model of renal tumorigenesis
Authors: Asrani Kaushal , Amaral Adrianna , Woo Juhyung , Abadchi Sanaz Nourmohammadi , Vidotto Thiago , Feng Kewen , Liu Hans B. , Kasbe Mithila , Baba Masaya , Oike Yuichi , Outeda Patricia , Watnick Terry , Rosenberg Avi Z. , Schmidt Laura S. , Linehan W. Marston , Argani Pedram , Lotan Tamara L. 
Published: November 2024

SummaryThe MiT/TFE family gene fusion proteins, such asSFPQ-TFE3, drive both epithelial (eg, translocation renal cell carcinoma, tRCC) and mesenchymal (eg, perivascular epithelioid cell tumor, PEComa) neoplasms with aggressive behavior. However, no prior mouse models forSFPQ-TFE3-related tumors exist and the mechanisms of lineage plasticity induced by this fusion remain unclear. Here, we demonstrate that constitutive murine renal expression of humanSFPQ-TFE3using Ksp Cadherin-Cre as a driver disrupts kidney development leading to early neonatal renal failure and death. In contrast, post-natal induction ofSFPQ-TFE3in renal tubular epithelial cells using Pax8 ERT-Cre induces infiltrative epithelioid tumors, which morphologically and transcriptionally resemble human PEComas. As seen in MiT/TFE fusion-driven human tumors,SFPQ-TFE3expression is accompanied by the strong induction of mTORC1 signaling, which is partially amino acid-sensitive and dependent on increasedSFPQ-TFE3-mediatedRRAGC/Dtranscription. Remarkably,SFPQ-TFE3expression is sufficient to induce lineage plasticity in renal tubular epithelial cells, with rapid down-regulation of the critical PAX2/PAX8 nephric lineage factors and tubular epithelial markers, and concomitant up-regulation of PEComa differentiation markers in transgenic mice, human cell line models and human tRCC. Pharmacologic or genetic inhibition of mTOR signaling downregulates expression of theSFPQ-TFE3fusion protein and rescues nephric lineage marker expression and transcriptional activityin vitro.These data provide evidence of a potential epithelial cell-of-origin forTFE3-driven PEComas and highlight a reciprocal role forSFPQ-TFE3and mTOR in driving lineage plasticity in the kidney, expanding our understanding of the pathogenesis of MiT/TFE-driven tumors.
Uncovering genetic linkages in the rhizosphere contributing to adaptation
Authors: Williams Jessica L. , Killian Erik Z. , Halpin-McCormick Anna , Kantar Michael B. , Sherman Jamie D. , Ewing Patrick M. , Eberly Jed O. , Lachowiec Jennifer 
Published: November 2024

AbstractMicroorganisms assembled into the plant rhizosphere from the surrounding soil can benefit the fitness of their host. Variation in plant genetics is associated with variation in rhizosphere microbial community composition leading to increased fitness and crop production and reducing reliance on synthetic agricultural inputs through selection. However, what impact the abiotic environment has on connections between microbes and host genetics, and whether those connections in turn impact crop performance in realistic agricultural scenarios is still unclear. We assessed agronomic performance and 16S sequence-based rhizosphere bacterial community composition on a large diverse barley population grown in seven field trials across four locations and two years. Within adapted regions, we observed consistent rhizosphere compositions across diverse soils, whereas in unadapted environments, distinct microbial communities were recruited, indicating environmental specificity in microbial assembly. Greenhouse trials further revealed that abiotic soil properties and microbial inoculants together interact to modulate rhizosphere composition and plant growth. Genome-wide association studies identified hundreds of quantitative trait loci (QTL) for microbial traits, with thirty of those loci co-localizing with agronomic traits, suggesting interspecies pleiotropy or genetic linkage. At specific loci, candidate genes associated with root-microbe interactions, including those related to pathogen response and root exudate production, suggest mechanisms that enable adaptation to local environments. These findings support the idea that genetic manipulation of rhizosphere microbiomes via selection of crops could enhance adaptation (i.e., yield, quality) across variable environments, advancing breeding strategies for improved crop resilience and productivity.
The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport
Authors: Brousseau Merissa , Teng Da , Thomas Nathan E. , Voth Gregory A. , Henzler-Wildman Katherine A. 
Published: November 2024

AbstractThe model multi-drug efflux pump fromEscherichia coli, EmrE, can perform multiple types of transport leading to different biological outcomes, conferring resistance to some drug substrates and enhancing susceptibility to others. While transporters have traditionally been classified as antiporters, symporters, or uniporters, there is growing recognition that some transporters may exhibit mixed modalities. This raises new questions about the regulation and mechanisms of these transporters. Here we show that the C-terminal tail of EmrE acts as a secondary gate, preventing proton leak in the absence of drug. Substrate binding unlocks this gate, allowing transport to proceed. Truncation of the C-terminal tail (Δ107-EmrE) leads to altered pH regulation of alternating access, an important kinetic step in the transport cycle, as measured by NMR. Δ107-EmrE has increased proton leak in proteoliposome assays and bacteria expressing this mutant have reduced growth. MD simulations of Δ107-EmrE show formation of a water wire from the open face of the transporter to the primary binding site in the core, facilitating proton leak. In WT-EmrE, the C-terminal tail forms specific interactions that block formation of the water wire. Together these data strongly support the C-terminus of EmrE acting as a secondary gate that regulates access to the primary binding site in the core of the transporter.