bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent profiling of multiscale 3D genome organization and gene expression in single mammalian cells
Authors: Zhou Tianming , Zhang Ruochi , Jia Deyong , Doty Raymond T. , Munday Adam D. , Gao Daniel , Xin Li , Abkowitz Janis L. , Duan Zhijun , Ma Jian 
Published: July 2023

AbstractThe organization of mammalian genomes within the nucleus features a complex, multiscale three-dimensional (3D) architecture. The functional significance of these 3D genome features, however, remains largely elusive due to limited single-cell technologies that can concurrently profile genome organization and transcriptional activities. Here, we report GAGE-seq, a highly scalable, robust single-cell co-assay that simultaneously measures 3D genome structure and transcriptome within the same cell. Employing GAGE-seq on mouse brain cortex and human bone marrow CD34+ cells, we comprehensively characterized the intricate relationships between 3D genome and gene expression. We found that these multiscale 3D genome features collectively inform cell type-specific gene expressions, hence contributing to defining cell identity at the single-cell level. Integration of GAGE-seq data with spatial transcriptomic data revealedin situvariations of the 3D genome in mouse cortex. Moreover, our observations of lineage commitment in normal human hematopoiesis unveiled notable discordant changes between 3D genome organization and gene expression, underscoring a complex, temporal interplay at the single-cell level that is more nuanced than previously appreciated. Together, GAGE-seq provides a powerful, cost-effective approach for interrogating genome structure and gene expression relationships at the single-cell level across diverse biological contexts.
HaploCatcher: An R Package for Prediction of Haplotypes
Authors: Winn Zachary James , Hudson-Arns Emily , Hammers Mikayla , DeWitt Noah , Lyerly Jeanette , Bai Guihua , St. Amand Paul , Nachappa Punya , Haley Scott , Mason Richard Esten 
Published: July 2023

ABSTRACTWheat (Triticum aestivumL.) is crucial to global food security, but is often threatened by diseases, pests, and environmental stresses. Wheat stem sawfly (Cephus cinctusNorton) poeses a major threat to food security in the United States, and solid-stem varieties, which carry the stem-solidness locus (Sst1), are the main source of genetic resistance against sawfly. Marker-assisted selection uses molecular markers to identify lines possessing beneficial haplotypes, like that of theSst1locus. In this study, an R package titled "HaploCatcher" was developed to predict specific haplotypes of interest in genome-wide genotyped lines. A training population of 1,056 lines genotyped for theSst1locus, known to confer stem solidness, and genome-wide markers was curated to make predictions of theSst1haplotypes for 292 lines from the Colorado State University wheat breeding program. PredictedSst1haplotypes were compared to marker derived haplotypes. Our results indicated that the training set was substantially predictive, with kappa scores of 0.83 for k-nearest neighbors and 0.88 for random forest models. Forward validation on newly developed breeding lines demonstrated that a random forest model, trained on the total available training data, had comparable accuracy between forward and cross-validation. Estimated group means of lines classified by haplotypes from PCR-derived markers and predictive modeling did not significantly differ. The HaploCatcher package is freely available and may be utilized by breeding programs, using their own training populations, to predict haplotypes for whole genome sequenced early generation material.CORE IDEASIdentification, introgression, and frequency increase of large effect loci are important for cultivar development.TheSst1locus has a significant effect on cutting score in fields exposed to sawfly infestation.Historical genetic information can be utilized to predict haplotypes for lines which have genome-wide genetic data.An R package, HaploCatcher, has been developed to facilitate this analysis in other programs.
RAPID ALKALINIZATION FACTOR 22 is a key modulator of the proliferation and hyper-elongation responses of root hairs to microbial volatiles in Arabidopsis
Authors: León Morcillo Rafael Jorge , Leal-López Jesús , López-Serrano Lidia , Baroja-Fernández Edurne , Gámez-Arcas Samuel , Doblas Verónica G. , Férez-Gómez Alberto , Pozueta-Romero Javier 
Published: July 2023

ABSTRACTRAPID ALKALINIZATION FACTOR (RALF) peptides are important players in regulating cell expansion. In Arabidopsis, volatile compounds (VCs) emitted by the fungal phytopathogenPenicillium aurantiogriseumpromote root hair (RH) proliferation and hyper-elongation through ethylene and enhanced photosynthesis signalling actions. A striking alteration in the proteome of fungal VC-treated roots involves up-regulation of RALF22. To test the possible involvement of RALF22 in the fungal VC-promoted RH changes, we characterized RH density and number responses to fungal VCs inralf22andfer-4plants impaired in RALF22 and its receptor FERONIA, respectively. Unlike WT plants,ralf22andfer-4RHs responded weakly to fungal VCs, strongly indicating that the RALF22-FERONIA module is a key determinant of the RH response to fungal VCs. To investigate the regulatory mechanisms behind this response, we analysed theRALF22transcript levels in roots ofetr1-3andeir1ethylene signalling mutants and those of ethylene-responsive, RH-relatedRSL4, RHD2, PRX1andPRX44transcripts inralf22andfer-4roots. Moreover, we characterized the RH andRALF22transcript level responses to fungal VCs of thecfbp1mutant defective in photosynthetic responsiveness to VCs. Unlike in WT roots, fungal VCs weakly enhancedRALF22expression inetr1-3, eir1andcfbp1roots, andRSL4, RHD2, PRX1andPRX44expression inralf22andfer-4roots. In addition, fungal VCs weakly promoted RH changes incfbp1roots. Collectively, our findings showed that the ethylene and enhanced photosynthesis signalling-mediated RH response to fungal VCs involves RALF22-FERONIA.
3 Directional Inception-ResUNet: deep spatial feature learning for multichannel singing voice separation with distortion
Authors: Wang DaDong , Wang Jie , Sun MingChen 
Published: July 2023

AbstractSinging voice separation on robots faces the problem of interpreting ambiguous auditory signals. The acoustic signal, which the humanoid robot perceives through its onboard microphones, is a mixture of singing voice, music, and noise, with distortion, attenuation, and reverberation. In this paper, we used the 3 directional Inception-Resnet structure in the U-shaped encoding and decoding network to improve the utilization of the spatial and spectral information of the spectrograms.Multi-objectives were used to train the model: magnitude consistency loss, phase consistency loss, and magnitude correlation consistency loss. We recorded the singing voice and accompaniment derived from the MIR-1k datasets with NAO robots and synthesized the 10-channel datasets for training the model. The experimental results show that the proposed model trained by multi-objective reaches an average NSDR of 11.55db on the test datasets, which outperforms the comparison model.Author summaryThe mixture in the real singing voice separation is always mixed with noise and distortion. In this paper, the acoustic signals with distortion and noise perceived by the robot are used to study the separation of singing voices in real scenes. This paper described how to synthesize the training datasets, proposed a 3 directional Inception-ResUNet structure for multichannel singing voice separation, and adopted multi-objectives including magnitude correlation consistency loss to train the model. The experimental results showed that the magnitude correlation consistency loss reduces distortions, the proposed model achieves better performance than the compared models.
FLECS Technology for High-Throughput Screening of Hypercontractile Cellular Phenotypes in Fibrosis: A Function-First Approach to Anti-Fibrotic Drug Discovery
Authors: Wang Yao , Cortes Enrico , Huang Ricky , Wan Jeremy , Hinz Boris , Damoiseaux Robert , Pushkarsky Ivan 
Published: July 2023

AbstractThe pivotal role of myofibroblast contractility in the pathophysiology of fibrosis is widely recognized, yet HTS approaches are not available to quantify this critically important function in drug discovery. We develop, validate, and scale-up a HTS platform that quantifies contractile function of primary human lung myofibroblasts upon treatment with pro-fibrotic TGF-β1. With the fully automated assay we screened a library of 40,000 novel small molecules in under 80 h of total assay run-time. We identified 42 hit compounds that inhibited the TGF-β1-induced contractile phenotype of myofibroblasts, and enriched for 19 that specifically target myofibroblasts but not phenotypically related smooth muscle cells. Selected hits were validated in anex vivolung tissue models for their inhibitory effects on fibrotic gene upregulation by TGF-β1. Our results demonstrate that integrating a functional contraction test into the drug screening process is key to identify compounds with targeted and diverse activity as potential anti-fibrotic agents.
Sensory event-related potential morphology predicts age in premature infants
Authors: Zandvoort Coen S. , van der Vaart Marianne , Robinson Shellie , Usman Fatima , Schmidt Mellado Gabriela , Evans Fry Ria , Worley Alan , Adams Eleri , Slater Rebeccah , Baxter Luke , de Vos Maarten , Hartley Caroline 
Published: July 2023

AbstractPreterm infants undergo substantial neurosensory development in the first weeks after birth. Infants born prematurely are more likely to have long-term adverse neurological outcomes and early detection of abnormal brain development is essential for timely interventions. We investigated whether sensory-evoked cortical potentials could be used to accurately estimate the age of an infant. Such a model could be used to identify infants who deviate from normal neurodevelopment by comparing the brain age to the infant’s postmenstrual age (PMA). Infants aged between 28- and 40-weeks PMA from a training and test sample (consisting of 101 and 65 recording sessions in 82 and 14 infants, respectively) received trains of approximately 10 visual and 10 tactile stimuli (interstimulus interval approximately 10 seconds). PMA could be predicted accurately from the magnitude of the evoked responses (training set mean absolute error (MAE and 95% confidence intervals): 1.41 [1.14; 1.74] weeks,p= 0.0001; test set MAE: 1.55 [1.21; 1.95] weeks,p= 0.0002. Moreover, we show with two examples that brain age, and the deviations between brain age and PMA, may be biologically and clinically meaningful. By firstly demonstrating that brain age is correlated with a measure known to relate to maturity of the nervous system (based on animal and human literature, the magnitude of reflex withdrawal is used) and secondly by linking brain age to long-term neurological outcomes, we show that brain age deviations are related to biologically meaningful individual differences in the rate of functional nervous system maturation rather than noise generated by the model. In summary, we demonstrate that sensory-evoked potentials are predictive of age in premature infants. It takes less than 5 minutes to collect the stimulus electroencephalographic data required for our model, hence, increasing its potential utility in the busy neonatal care unit. This model could be used to detect abnormal development of infant’s response to sensory stimuli in their environment and may be predictive of later life abnormal neurodevelopmental outcome.
Consistent decrease in conifer embolism resistance from the stem apex to base resulting from axial trends in tracheid and pit traits
Authors: Dario Zambonini , Tadeja Savi , Sabine Rosner , Giai Petit 
Published: July 2023

AbstractDrought-induced embolism formation in conifers is associated with several tracheid and pit traits, which vary in parallel from stem apex to base. We tested whether this axial anatomical variability is associated with a progressive variation in embolism vulnerability along the stem from apex to base.We assessed the xylem pressure at 50% loss of conductivity (P50), the tracheid hydraulic diameter (Dh) and mean pit membrane area (PMA) on longitudinal stem segments extracted at different distances from the stem apex (DFA) in aPicea abiesand anAbies albatree. In both trees,DhandPMAscaled withDFA0.2.P50varied for more than 3 MPa from the treetop to the stem base, according to a scaling of -P50withDFA-0.2. The largestDh,PMAandP50variation occurred forDFA<1.5 m.PMAandDhscaled isometrically (exponentb=1).Pit traits vary proportionally with tracheid lumen diameter. Apex-to-base trends in tracheid and pit traits determine a largeDFA-dependentP50variability. Such aDFAeffect onP50did not receive sufficient attention so far, although analysing the relationshipsP50vs.DFAis fundamental for the assessment of embolism vulnerability at the individual level.HighlightsConifer embolism vulnerability depends on pit properties, in agreement with published data.Pit dimensions increase with tracheid lumen diameter, in agreement with published dataTracheid lumen diameter and pit dimensions increase progressively from the stem apex to base, in agreement with published data.Xylem vulnerability to embolism formation (P50) varies for > 3 MPa from the stem apex to base, with the largest variation occurring within 1.5 m from the stem apex.Axial anatomical patterns should be accounted for when analyzing hydraulic properties at individual, intra- and inter-specific scales.
Changes in spatial self-consciousness elicit grid cell-like representation in entorhinal cortex
Authors: Moon Hyuk-June , Albert Louis , Falco Emanuela De , Tasu Corentin , Gauthier Baptiste , Park Hyeong-Dong , Blanke Olaf 
Published: July 2023

AbstractGrid cells in entorhinal cortex (EC) encode an individual’s location in space and rely on environmental cues and multisensory bodily cues. Body-derived signals are also primary signals for the sense of self as the continuous application of visuo-tactile bodily stimuli elicits illusory drifts in perceived self-location. It is unknown whether illusory changes in self-location are sufficient to elicit grid cell like representation (GCLR) in EC and how this compares to GCLR during conventional virtual navigation. Our results show that illusory changes in perceived self-location (independent of changes in environmental navigation cues and explicit imagined navigation) evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues.
Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis
Authors: Widder Stefanie , Opron Kristopher , Carmody Lisa A. , Kalikin Linda M. , Caverly Lindsay J. , LiPuma John J. 
Published: July 2023

AbstractPolymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease (COPD). Intermittent pulmonary exacerbations (PEx) in these conditions are associated with lung function decline and higher mortality rates. An understanding of the microbial underpinnings of PEx is challenged by high inter-patient variability in airway microbial community profiles. We analyzed 880 near-daily CF sputum samples and developed non-standard microbiome descriptors to model community reorganization prior and during 18 PEx. We identified two communal microbial regimes with opposing ecology and dynamics. Whereas pathogen-governed dysbiosis showed hierarchical community organization and reduced diversity, anaerobic bloom dysbiosis displayed stochasticity and increased diversity. Microbiome organization modulated the relevance of pathogens and a simulation of antimicrobial treatment predicted better efficacy for hierarchically organized microbiota. This causal link between PEx, microbiome organization, and treatment success advances the development of personalized dysbiosis management in CF and, potentially, other obstructive lung diseases.
Mobile version of the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA): Implementation and adult norms
Authors: Bella Simone Dalla , Foster Nicholas E.V. , Laflamme Hugo , Zagala Agnès , Melissa Kadi , Komeilipoor Naeem , Blais Mélody , Rigoulot Simon , Kotz Sonja A. 
Published: July 2023

AbstractTiming and rhythm abilities are complex and multidimensional skills that are highly widespread in the general population. This complexity can be partly captured by the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA). The battery, consisting of 4 perceptual and 5 sensorimotor tests (finger tapping), has been used in healthy adults and in clinical populations (e.g., Parkinson’s disease, ADHD, developmental dyslexia, stuttering), and shows sensitivity to individual differences and impairment. However, major limitations for the generalized use of this tool are the lack of reliable and standardized norms and of a version of the battery that can be used outside the lab. To circumvent these caveats we put forward a new version of BAASTA on a tablet device capable of ensuring lab-equivalent measurements of timing and rhythm abilities. We present normative data obtained with this version of BAASTA from over 100 healthy adults between the ages of 18 and 87 years in a test-retest protocol. Moreover, we propose a new composite score to summarize beat-based rhythm capacities, the Beat Tracking Index (BTI), with close to excellent test-retest reliability. BTI derives from two BAASTA tests (beat alignment, paced tapping), and offers a swift and practical way of measuring rhythmic abilities when research imposes strong time constraints. This mobile BAASTA implementation is more inclusive and far-reaching, while opening new possibilities for reliable remote testing of rhythmic abilities by leveraging accessible and cost-efficient technologies.
Length-dependent RNA foci formation and RAN translation are associated with SCA12 disorder
Authors: Kumar Manish , Sahni Shweta , Anand Vivek , Kumar Deepak , Kushwah Neetu , Goel Divya , Kapoor Himanshi , Srivastava Achal K , Faruq Mohammed 
Published: July 2023

SummarySpinocerebellar ataxia type-12 (SCA-12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5’-UTR/non-coding region ofPPP2R2B. Molecular pathology of SCA12 has not been studied in the context of CAG repeats and no appropriate models exist. We found in human SCA12-iPSC derived neuronal lineage that expanded CAG inPPP2R2Btranscript forms nuclear RNA foci and were found to sequester variety of proteins. Further, the ectopic expression of transcript containing varying length of CAG repeats exhibits non-canonical Repeat Associated Non-AUG (RAN) translation in multiple frames in HEK293T cells, which was further validated in patient-derived neural stem cells using specific antibodies. mRNA sequencing of the SCA12 and control neurons have shown a network of crucial transcription factors affecting neural fate, in addition to alteration of various signaling pathways involved in neurodevelopment. Altogether, this study identifies the molecular signatures of spinocerebellar ataxia type-12 disorder using patient-derived neuronal cell lines.
Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions
Authors: Omo-Lamai Serena , Zamora Marco E. , Patel Manthan N. , Wu Jichuan , Nong Jia , Wang Zhicheng , Peshkova Alina , Chase Liam S. , Essien Eno-Obong , Muzykantov Vladimir , Marcos-Contreras Oscar , Myerson Jacob W. , Brenner Jacob S. 
Published: July 2023

AbstractLipid nanoparticles (LNPs) have become the dominant drug delivery technology in industry, holding the promise to deliver RNA to up- or down-regulate any protein of interest. LNPs have been targeted to specific cell types or organs by physicochemical targeting, in which LNP’s lipid compositions are adjusted to find mixtures with the desired tropism. In a popular approach, physicochemical targeting is accomplished by formulating with charged lipids. Negatively charged lipids localize LNPs to the spleen, and positively charged lipids to the lungs. Here we found that lung-tropic LNPs employing cationic lipids induce massive thrombosis. We demonstrate that thrombosis is induced in the lungs and other organs, and greatly exacerbated by pre-existing inflammation. This clotting is induced by a variety of formulations with cationic lipids, including LNPs and non-LNP nanoparticles. The mechanism depends on the LNPs binding to fibrinogen and inducing platelet and thrombin activation. Based on these mechanisms, we engineered multiple solutions which enable positively charged LNPs to target the lungs while not inducing thrombosis. Our findings implicate thrombosis as a major barrier that blood erects against LNPs with cationic components and illustrate how physicochemical targeting approaches must be investigated early for risks and re-engineered with a careful understanding of biological mechanisms.
Meta-colored compacted de Bruijn graphs
Authors: Pibiri Giulio Ermanno , Fan Jason , Patro Rob 
Published: July 2023

AbstractMotivationThe colored compacted de Bruijn graph (c-dBG) has become a fundamental tool used across several areas of genomics and pangenomics. For example, it has been widely adopted by methods that perform read mapping or alignment, abundance estimation, and subsequent downstream analyses. These applications essentially regard the c-dBG as a map fromk-mers to the set of references in which they appear. The c-dBG data structure should retrieve this set — thecolorof thek-mer — efficiently for any givenk-mer, while using little memory. To aid retrieval, the colors are stored explicitly in the data structure and take considerable space for large reference collections, even when compressed. Reducing the space of the colors is therefore of utmost importance for large-scale sequence indexing.ResultsWe describe themeta-coloredcompacted de Bruijn graph (Mac-dBG) — a new colored de Bruijn graph data structure where colors are represented holistically, i.e., taking into account their redundancy across the whole collection being indexed, rather than individually as atomic integer lists. This allows the factorization and compression of common sub-patterns across colors. While optimizing the space of our data structure is NP-hard, we propose a simple heuristic algorithm that yields practically good solutions. Results show that the Mac-dBG data structure improves substantially over the best previous space/time trade-off, by providing remarkably better compression effectiveness for the same (or better) query efficiency. This improved space/time trade-off is robust across different datasets and query workloads.Code availabilityAC++17implementation of the Mac-dBG is publicly available on GitHub at:https://github.com/jermp/fulgor.