bluuebunny/crossref_metadata_2025_split huggingface dataset:
Horizontal gene transfer-initiated reorganization of lipid metabolism drives lifestyle innovation in a eukaryote
Authors: Rao Bhagyashree Dasari , Gomez Gil Elisa , Peter Maria , Balogh Gabor , Nunes Vanessa , MacRae James I. , Chen Qu , Rosenthal Peter , Oliferenko Snezhana 
Published: August 2024

AbstractHorizontal gene transfer is a source of metabolic innovation and adaptation to new environments. Yet, how horizontally transferred metabolic functionalities are integrated into host cell biology remains an open question. Here, we use the fission yeast Schizosaccharomyces japonicus to probe how eukaryotic lipid metabolism is rewired in response to the acquisition of a horizontally transferred squalene-hopene cyclase Shc1. We show that Shc1-dependent production of hopanoids, the structural mimics of eukaryotic sterols, allows S. japonicus to thrive in anoxia, where sterol biosynthesis is not possible. We further demonstrate that glycerophospholipid fatty acyl asymmetry, prevalent in S. japonicus, is crucial for accommodating both sterols and hopanoids in membranes, and explain how Shc1 functions alongside the native sterol biosynthetic pathway to support membrane properties. Through engineering experiments in the sister species S. pombe, which naturally lacks Shc1, we show that the acquisition of Shc1 may entail new physiological traits; however, to maximize Shc1 performance, sterol biosynthesis must be dampened. Our work sheds new light on the mechanisms underlying cellular integration of horizontally transferred genes in eukaryotes and provides broader insights into the evolution of membrane organization and function.
Testing and overcoming the limitations of Modular Response Analysis
Authors: Borg Jean-Pierre , Colinge Jacques , Ravel Patrice 
Published: August 2024

AbstractModular Response Analysis (MRA) is an effective method to infer biological networks from perturbation data. However, it has several limitations, such as strong sensitivity to noise, need of performing independent perturbations that hit a single node at a time, and linear approximation of dependencies within the network. Previously, we addressed MRA sensitivity to noise by revisiting MRA as a multilinear regression problem. Here, we provide new contributions to complement this theory. First, we overcame the need of perturbations to be independent, thereby augmenting MRA applicability. Second, using analysis of variance (ANOVA) and lack of fit tests, we assessed MRA compatibility with the data and identified the primary source of errors. If nonlinearity prevails, we propose a polynomial extension to the model. Third, we demonstrated how to effectively use the prior knowledge of the network studied. Finally, we added these innovations to our R software package MRARegress to provide a complete, extended theory around MRA and to facilitate its access by the community.
Therapeutically targeting the classical complement pathway with antisense oligonucleotides in Alzheimer’s disease
Authors: Wang Yuanyuan , Wu Tiffany , Gogineni Alvin , Tsai Ming-Chi , Kielpinski Lukasz , Mahajan Anubha , Pandey Shristi , Schachner Luis , Tran John C. , Wu Cong , Schauer Stephen , Biever Anne , Boesen Sidsel , Li Meiling , Munk Alexander , Meilandt William J , Elstrott Justin , Easton Amy , Gylling Helene M , Hanson Jesse E 
Published: August 2024

AbstractThe complement classical pathway (CP) is a key mediator of synapse loss and neurodegeneration in mouse models of Alzheimer’s (AD) and other neurodegenerative diseases. We analyzed human brain proteomics and found consistent elevations of all CP proteins, but not other complement pathways, in AD patient brains. We performed human genetics analysis that identified a rare variant in theC1Sgene within the Finnish population that is associated with AD and we found that a common AD-associatedC1Svariant correlates with increased C1S protein levels. A targeted assay detected elevated C1S activation in AD patient CSF. Given this specific implication of the CP in AD, we next evaluated the therapeutic approach of targeting the CP in the brain using antisense oligonucleotides (ASOs). To identify promising CP targets for knockdown using ASOs we first tested for rescue of synapse loss in an AD mouse model using heterozygous and homozygous complement knockout mice and examined the relative brain expression levels of different CP genes. Based on these experiments we prioritized C1r, C1s and C4 as promising targets for therapeutic knockdown using ASOs. We then screened for ASOs for each target, evaluatingin vitroandin vivoknockdown and toxicity, and identified optimal ASOs targeting C1r, C1s and C4. Experiments with AD model mice demonstrated significant rescue of synapse loss following treatment with C1r, C1s or C4 ASOs. Overall, our findings provide proof of concept for using nucleic acid-based medicine to target the CP in AD and demonstrate the translational potential of this approach.
Unlocking new avenues for non-invasive brain monitoring with combined electroencephalography and functional magnetic resonance imaging at ultra-high field
Authors: Sainz Martinez Cristina , Wirsich Jonathan , Jäger Cilia , Warbrick Tracy , Vulliémoz Serge , Lemay Mathieu , Bastiaansen Jessica , Wiest Roland , Jorge João 
Published: August 2024

AbstractThe combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) at ultra-high field (7 Tesla) offers unprecedented possibilities to probe human brain function non-invasively with high coverage, millisecond temporal precision and sub-millimeter spatial precision, unraveling cortical layers and small subcortical structures. Unfortunately, this technique has remained largely inaccessible at 7T, due to prohibitive cross-modal interference effects and physical constraints. Here, we developed a first-of-its-kind EEG-fMRI acquisition framework on a clinical 7T system combining key improvements from previous works: compact EEG transmission chain to reduce artifact incidence, reference sensors for artifact correction, and adapted leads for compatibility with a dense radiofrequency receive-array allowing state-of-the-art fMRI sensitivity and acceleration. Two implementations were tested: one using an EEG cap adapted in-house, and another using a recently-designed prototype from an industrial manufacturer, intended to be further developed into a commercial product accessible to the broader community. A comprehensive evaluation in humans showed that simultaneous acquisitions, including with sub-millimeter fMRI resolution, could be conducted without detectable safety issues or major practical constraints. The EEG exerted relatively mild perturbations on fMRI quality (6–11% loss in temporal SNR), without measurably affecting the detection of resting-state networks and visual responses. The artifacts induced on EEG could be corrected to a degree where the spatial, spectral and temporal characteristics were comparable to outside recordings, and hallmark features such as resting-state alpha and eyes-closing alpha modulation could be clearly detected. Altogether, these findings indicate excellent prospects for neuroimaging applications, that can leverage the unique possibilities achievable at 7T.
Reduction of SEM charging artefacts in native cryogenic biological samples
Authors: Velazco Abner , Glen Thomas , Klumpe Sven , Pennington Avery , Zhang Jianguo , Smith Jake LR , Glynn Calina , Bowles William , Kobylynska Maryna , Fleck Roland A. , Naismith James H. , Kim Judy S , Darrow Michele C. , Grange Michael , Kirkland Angus I , Dumoux Maud 
Published: August 2024

AbstractScanning electron microscopy (SEM) of frozen-hydrated biological samples allows imaging of subcellular structures at the mesoscale in their native state. Combined with focused ion beam milling (FIB), serial FIB/SEM can be used to build a 3-dimensional picture of cells and tissues. The correlation of specific regions of interest with cryo-electron microscopy (cryoEM) can additionally enable subsequent high-resolution analysis. However, the adoption of serial FIB/SEM imaging-based methods is limited due to artefacts arising from insulating areas of cryogenically preserved samples. Here, we demonstrate the use of interleaved scanning to reduce charging artefacts, allowing the observation of biological features that otherwise would be masked or perturbed. We apply our method to samples where inherent features are not visible. These examples include membrane contact sites within mammalian cells, visualisation of the degradation compartment in the algae E.gracilis and observation of a network of membranes within different types of axons in an adult mouse cortex. We further propose an alternative scanning method that could also be widely applicable to imaging any non-conductive.
Spatio-temporal segmentation of contraction waves in the extra-embryonic membranes of the red flour beetle
Authors: Pereyra Marc , Golden Mariia , Lange Zoë , Golden Artemiy , Strobl Frederic , Stelzer Ernst H.K. , Matthäus Franziska 
Published: August 2024

AbstractIn this paper, we introduce an image analysis approach for spatio-temporal segmentation, quantification and visualization of movement or contraction patterns in 2D+t or 3D+t microscopy recordings of biological tissues. The imaging pipeline is applied to time lapse images of the embryonic development of the red flour beetleTribolium castaneumrecorded with light-sheet fluorescence microscopy (LSFM). We are particularly interested in the dynamics of extra-embryonic membranes, and provide quantitative evidence of the existence of contraction waves during late stages of development. These contraction waves are a novel observation of which neither origin, nor function are yet known. The proposed pipeline relies on particle image velocimetry (PIV) for quantitative movement analysis, surface detection, tissue cartography, and an algorithmic approach to detect characteristic movement dynamics. This approach locates contraction waves in 2D+t and 3D+t reliably and efficiently and allows the automated quantitative analysis, such as the area involved in the contractile behavior, contraction wave duration and frequency, path of contractile area, or the relation to the spatio-temporal velocity distribution. The pipeline will be used in the future to conduct a large-scale characterization and quantification of contraction wave behavior inTribolium castaneumdevelopment and can be adapted easily to the identification and segmentation of characteristic tissue dynamics in other systems of interest.
Functional high capacity exosome-encapsulating bioinspired hydrogel promotes microvascular bed expansion in diabetic mice
Authors: Subhan Bibi S , Cortes Troncoso Juan F , Katyal Priya , Meleties Michael , Mestvirishvili Tamara , Arias Fernando , Wang Andrew , Ruggles Kelly , Dolgalev Igor , Mita Paolo , Montclare Jin Kim , Rabbani Piul S 
Published: August 2024

AbstractChronic wounds present a significant clinical challenge due to impaired skin microvasculature, particularly in diabetes. The tissue engineering study introduces therapeutic Exo-Q, a unique thermoresponsive polymer hydrogel created with Q protein nanofibers and cultured human bone marrow multipotent stromal cell exosomes with consistent gene signature. Limited, local and topical application of Exo-Q hydrogel is feasible for maximum neovascularization during murine diabetic wound closure in a xenotransplantation model, as well as compatibility and vascular delivery in human skin in a xenograft model. Exo-Q hydrogel treatment significantly reduces diabetic wound closure time within ranges of non-diabetic wounds. This innovative, non-invasive tissue engineered therapeutic option offers a promising approach to addressing the complex pathologies of non-healing wounds.
Increased Postprandial Metabolic Flexibility is Associated with Higher Body Fat Percentages in Healthy Young Adults
Authors: Foreman Nicholas A. , Rajwade Sahil , Bluth Jaiden , Skoglund Lauren C. , Letts Audrey M. , DiPietro Loretta , Ciarleglio Adam , Barberio Matthew D. 
Published: August 2024

AbstractPURPOSEHigh levels of adiposity are associated with an increased risk for chronic cardiometabolic disease. Adipose tissue is a critical metabolic tissue during the postprandial (feeding) period. We sought to assess the relationship between body composition (body fat percentage) and measures of postprandial metabolic flexibility in otherwise healthy young adults.METHODSYoung adults (n = 27, n = 15 females) of varying body compositions (BMI = 27.1 ± 4.5; Body Fat (BF)% = 30.4 ± 8.7) but without overt pathology completed a 100g oral glucose tolerance test (OGTT). Indirect calorimetry was conducted before (fasting) and following (30, 60, 90, 120 min) consumption of the glucose beverage. Serum and plasma were collected at corresponding time points and analyzed for blood glucose, insulin, non-esterified fatty acids, and inflammatory markers. Linear mixed models were used to test for the effect of body composition on postprandial metabolism over time while controlling for sex, age, fasting metabolism, measures of insulin sensitivity, visceral adipose tissue volume, and the repeated measures design.RESULTSAs expected, there was a significant (p < 0.05) increase in blood glucose, serum insulin, RER, and CHO with concomitant decreases in plasma NEFAs and whole-body FOX during the OGTT. Using mixed effects models, BF% modified the relationship between postprandial RER and time (β= -0.133, p = 0.019), as well as postprandial CHO and time (β= -0.134, p = 0.023) such that individuals with higher BF% increase their RER and CHO at a greater rate and to a greater extent than those with lower BF%. There was no evidence that BF% modifies the relationship between FOX and time.CONCLUSIONWe demonstrate that a higher body fat percentage is associated with greater postprandial metabolic flexibility (RER and CHO) during an OGTT in young adults without overt metabolic pathology. Metabolic flexibility in this sample may be preserved and represents a compensatory adaptation to decreased glucose storage in the anabolic, postprandial period.
Universal features of Alternative splicing in response to diverse environmental stimuli in rice and the vital roles of TFs in AS regulation
Authors: Xiao Benze , Yang Shuai , Wang Chengqi , Zhang Fangyu , Liu Yi , Xiao Zhuowei , Xie Guosheng , Zhang Zhengfeng 
Published: August 2024

AbstractBackgroundPre-mRNA alternative splicing (AS) plays essential roles in response to environmental stimuli in plants. However, the universal and specific features of splicing in response to diverse environmental conditions remain not fully understood. Recent studies have shown the co-transcriptional characteristics of splicing, which lead to the reasonable speculation that the elements or factors regulating transcription can also affect splicing. Among of which, the effects of transcription factors on alternative splicing in plants under environmental stimuli are still confusing. A large amount 0f public available RNA sequencing data are valuable resources to be re-analyzed for answering questions beyond the aims of their original studies.ResultsWe explored the universal features of AS using a standard RNA-seq dataset TENOR, which stems from rice samples under controlled diverse conditions to provide comprehensive and comparable AS analysis under various conditions. We found that AS widely occurs in rice under stimuli, with significant tissue specificity, temporal dynamics, commonality among different stresses or treatments as well as significant difference between differential alternative splicing and expressed genes (DASGs and DEGs) in rice under environmental stimuli. The majority of DASGs under various stresses are splicing factors and transcription factors. The correlation analysis shows that the expression level of transcription factors is significantly correlated with the PSI of AS events. The predominant transcription factors correlating with alternative splicing events come from bHLH, bzip and hsfa families. We validated the effects of transcription factors on AS by analyzing RNA-seq data from transcription factor mutants and found substantial differential AS events between mutants and wild type. Furthermore, the significant correlation was discovered between the transcription levels of transcription factors and splicing factors.ConclusionWe found universal features of AS and the predominant AS events of SFs and TFs in plants under diverse environments. We propose that TFs might regulated AS of download genes partly by changing the patterns of their own transcription and splicing to further regulate the transcription of SFs. This work illuminate the studies on the possible mechanisms by which TFs modulate AS in plant, especially under environmental stimuli.
Longitudinally cultured precision cut lung slices as a predictiveex vivomodel for lung cancer
Authors: Sargsian Ara , Girmatsion Hermon , Lenders Vincent , Ghesquière Bart , Takeno Cologna Camila , Soenen Stefaan J. , Manshian Bella B. 
Published: August 2024

AbstractExploring alternatives toin vivomodels, this study validates Precision Cut Lung Slices (PCLS) as a viableex vivoplatform for lung cancer research. We established the prolonged viability and structural preservation of PCLS, essential for accurate drug response studies. Using Paclitaxel as a benchmark drug and a therapeutically promising silver nanoparticles in combination with immunotherapy, we conducted a pioneering comparative analysis of its therapeutic effects on PCLS against traditionalin vivomodels. Results revealed that PCLS closely mimicsin vivoresponses, demonstrating comparable drug efficacy in tumor growth inhibition. This direct comparison not only confirms the utility of PCLS in simulating real-world outcomes but also emphasizes its potential in reducing animal testing. By providing a reliable, ethical, and efficient alternative for lung cancer studies, PCLS could significantly enhance preclinical research and drug development, marking a critical step towards more humane and representative scientific investigations.
Pelvic floor health in athletics: a cross-sectional study at the Lima World Athletics U20 Championships
Authors: Silvia Giagio , Stephane Bermon , Frederic Garrandes , Tamara Rial Rebullido , Paolo Pillastrini , Marco Vecchiato , Emilio Adami Paolo 
Published: August 2024

ABSTRACTObjectivesThis study aims to investigate various aspects of pelvic floor health among male and female athletes participating in the Lima World Athletics U20 Championships.MethodsThis observational, cross-sectional study will be conducted through a web-based survey via SurveyMonkey. The survey will collect demographic and anthropometric data, as well as medical history, including any injuries to the lower abdomen or pelvic area and history of urinary tract infections. It will also gather information on athletics-related characteristics, such as event specialization, training intensity, and competition volume. Additionally, the survey will explore pelvic floor health by assessing athletes’ knowledge of pelvic floor function and dysfunctions, as well as related behaviors. The prevalence rates of pelvic floor dysfunction (PFD) —including urinary and anal incontinence, pelvic pain, overactive bladder, and pelvic organ prolapse—will be assessed, along with their impact on sports participation and potential risk factors. Urinary incontinence will be further evaluated using the International Consultation on Incontinence Questionnaire-UI Short-Form (ICIQ-UI-SF), with a focus on identifying specific triggers related to athletic activities. Participants will also provide information about their experiences with pelvic floor screening, discussions about these issues, symptom management strategies, and any medical assessments or treatments they have received. Data will be analyzed using descriptive statistics and subgroup analyses. Correlation between collected variables and the presence of PFD will be investigated using correlation analyses.ConclusionThe findings from this study will provide valuable insights into the unique challenges faced by young elite athletes concerning pelvic floor health. This research represents an initial step toward an international initiative, promoted by World Athletics, to enhance pelvic floor health surveillance and promote overall well-being in athletics.
A tactile discrimination task to study neuronal dynamics in freely-moving mice
Authors: Heimburg Filippo , Saluti Nadin Mari , Timm Josephine , Adlakha Avi , Castelanelli Melina , Klumpp Matthias , Embray Lee , Both Martin , Draguhn Andreas , Kuner Thomas , Groh Alexander 
Published: August 2024

AbstractSensory discrimination tasks are valuable tools to study neuronal mechanisms of perception and learning. Most of the previously developed discrimination tasks for electrophysiological and imaging studies in rodents require the animals to be head-fixed. However, implementing neurophysiological recordings into more ethologically realistic settings with unrestrained animals has been challenging, especially for somatosensory studies. This study introduces a tactile discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, mice learn to discriminate between different aperture widths within days in order to forage for food rewards on a linear platform. We demonstrate that the task is whisker-dependent and that mice reliably discriminate aperture differences as small as 6 mm. The setup’s versatility enables exploration into diverse behavioral aspects, including tactile discrimination thresholds, valence-dependent behavior, and cognitive flexibility following repeated task rule reversals. Rule learning was highly stereotypical, fast and reproducible across individual mice, with approximately 500 trials to attain expert level performance and approximately 1000 trials to relearn the first rule reversal. We further demonstrate that electrophysiological recordings and calcium imaging can be conducted in the same paradigm such that multiple behavioral read-outs (learning progression, whisker motion, whisker touch, reward licking) can be synchronized with respective electrophysiological and imaging data, providing a new versatile tool to elucidate neural mechanisms of cognition and sensory processing.