bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical Bayes spline model learns multi-way genomic interactions from single cell 3D genome data
Authors: Park Kwangmoon , Keleş Sündüz 
Published: April 2024

AbstractA number of foundational analysis methods have emerged for single cell chromatin conformation (scHi-C) datasets capturing 3D organizations of genomes at the single cell resolution; however, these scHi-C datasets are currently under-utilized. The canonical uses of the existing scHi-C data encompass, beyond standard cell type identification through clustering and trajectory analysis, inference of chromosomal structures such as topologically associated domains, A/B compartments, and pairwise interactions. However, multi-way interactions, e.g., looping among multiple genomic elements such as multiple enhancers of a gene, are entirely overlooked. We introduceELECT, an empirical Bayes modelling framework toExtract muLti-way gEnomiCinTeractions by leveraging scHi-C data. ELECT builds on a dirichlet-multinomial spline model, incorporates well-known genomic distance bias of the chromatin conformation capture data, and yields multi-way interaction scores by leveraging corresponding pairwise interactions across cells of the same type. The multinomial-poisson transformation enables parameter estimation and inference for ELECT in a computationally feasible way for both low and high resolution single cell chromatin conformation data. ELECT yields well-calibrated p-values for controlling the false discovery rate and inferring multi-way interactions. We applied ELECT to both low and high resolution scHi-C datasets and carried out evaluations with external genomic and epigenomic data including data from DNA methylation, SPIRITE, scNanoHi-C, and DNA seqFISH+ assays. Application of ELECT to scHi-C data from human prefrontal cortex revealed multi-way interactions that involved GWAS SNPs associated with psychiatric disorders including autism and major depressive disorder, suggesting ELECT’s potential for interrogating genomewide association studies for epistasis. ELECT is publicly available athttps://github.com/keleslab/elect.
Silybin A fromSilybum marianumreprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids
Authors: Koeberle Solveigh C. , Thürmer Maria , Werner Markus , Grander Julia , Hofer Laura , Gollowitzer André , Su Fengting , Le Xuan Loc , Benscheid Felix J. , Bonyadi Rad Ehsan , Zarrelli Armando , Di Fabio Giovanni , Werz Oliver , Romanucci Valeria , Lupp Amelie , Koeberle Andreas 
Published: April 2024

AbstractSilybum marianumis used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation of membrane protein function, and metabolic regulation have been discussed for decades. Here, we show that specifically the stereoisomer silybin A decreases triglyceride levels and lipid droplet content, while enriching major phospholipid classes and maintaining a homeostatic phospholipid composition in human hepatocytesin vitroand in mouse liverin vivounder normal and pre-disease conditions. Conversely, in cell-based disease models of lipid overload and lipotoxic stress, silybin treatment primarily depletes triglycerides. Mechanistically, silymarin/silybin suppresses phospholipid-degrading enzymes, induces phospholipid biosynthesis to varying degrees depending on the conditions, and down-regulates triglyceride biosynthesis, while inducing complex changes in sterol and fatty acid metabolism. Structure-activity relationship studies highlight the importance of the 1,4-benzodioxane ring configuration of silybin A in triglyceride reduction and the saturated 2,3-bond of the flavanonol moiety in phospholipid accumulation. Enrichment of hepatic phospholipids and intracellular membrane expansion are associated with an heightened biotransformation capacity. In conclusion, our study deciphers the structural features of silybin contributing to hepatic lipid reorganization and offers insights into its liver-protective mechanism, potentially involving a context-dependent lipid class switch from triglycerides to phospholipids.
An integrative single-cell atlas to explore the cellular and temporal specificity of neurological disorder genes during human brain development
Authors: Kim Seoyeon , Lee Jihae , Koh In Gyeong , Ji Jungeun , Kim Hyun Jung , Kim Eunha , Park Jihwan , Park Jong-Eun , An Joon-Yong 
Published: April 2024

AbstractSingle-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to the developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expressions under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of developing human brains, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder genes. Lineages of non-neuronal cells determined by molecular profiles also showed temporal-specific expressions, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types for neuronal disorders, indicative of the prenatal stage’s influence on disease determination. Our findings facilitate unbiased comparisons of cell type-disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.
Dopamine D2R and opioid MOR availability in autism spectrum disorder
Authors: Noppari Tuomo , Tuisku Jouni , Lukkarinen Lasse , Tani Pekka , Lindberg Nina , Saure Emma , Lauerma Hannu , Tiihonen Jari , Hirvonen Jussi , Helin Semi , Rajander Johan , Salmi Juha , Nummenmaa Lauri 
Published: April 2024

AbstractOpioid and dopamine receptor systems are implicated in the pathoetiology of autism, butin vivohuman brain imaging evidence for their role remains elusive. Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11C]raclopride (D2R) and [11C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 19 age and sex matched controls. Regional group differences in D2R and MOR receptor availabilities were tested with linear mixed models and associations between regional receptor availabilities were examined with correlations. There were no group differences in whole-brain voxel-wise analysis of DR2 but ROI analysis presented a lower overall mean D2R availability in striatum of the ASD versus control group. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens of the ASD group. The whole-brain voxel-wise analysis of MOR revealed precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens. These alterations may translate to disrupted modulation of social motivation and reward in ASD.
A novel barcoded nanopore sequencing workflow of high-quality, full-length bacterial 16S amplicons for taxonomic annotation of bacterial isolates and complex microbial communities
Authors: Dommann Julian , Kerbl-Knapp Jakob , Torres Diana Albertos , Egli Adrian , Keiser Jennifer , Schneeberger Pierre H. H. 
Published: April 2024

AbstractIntroductionDue to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, i) identification of bacterial isolates and ii) species-level profiling of microbial communities.MethodsBacterial isolate identification by sequencing was tested on 47 isolates and compared to MALDI-TOF MS. 97 isolates were additionally sequenced to assess the resolution of phylogenetic classification. Species-level community profiling was tested with two full-length 16S primer pairs (A and B) with custom barcodes and compared to results obtained with Illumina sequencing using 27 stool samples. Finally, a Nextflow pipeline was developed to produce high-quality reads and taxonomically annotate them.ResultsWe found high agreement between our workflow and MALDI-TOF data for isolate identification (PPV = 0.90, Cramér’s V = 0.857 and, Theil’s U = 0.316). For species-level community profiling, we found strong correlations (rs> 0.6) of alpha diversity indices between the two primer sets and Illumina sequencing. At the community level, we found significant but small differences when comparing sequencing techniques. Finally, we found moderate to strong correlation when comparing relative abundances of individual species (average rs= 0.6 and 0.533, for primers A and B).DiscussionThe proposed workflow enabled accurate identification of single bacterial isolates, making it a worthwhile alternative to MALDI-TOF. While shortcomings have been identified, it enabled reliable identification of prominent features in microbial communities at a fraction of the cost of Illumina sequencing.ImportanceA quick, robust, simple, and cost-effective method to identify bacterial isolates and communities in each sample is indispensable in the fields of microbiology and infection biology. Recent technological advances in Oxford Nanopore Technologies sequencing make this technique an attractive option considering the adaptability, portability, and cost-effectiveness of the platform. Here, we validated a flexible workflow to identify bacterial isolates and characterize bacterial communities using the Oxford Nanopore Technologies sequencing platform combined with the most recent v14 chemistry kits. For bacterial isolates, we compared our nanopore-based approach to MALDI-TOF MS-based identification. For species-level profiling of complex bacterial communities we compared our nanopore-based approach to Illumina shotgun sequencing. For reproducibility purposes, we wrapped the code used to process the sequencing data into a ready-to-use and self-contained Nextflow pipeline.
Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole- to triphosphate-activation
Authors: DasGupta Saurja , Weiss Zoe , Nisler Collin , Szostak Jack W. 
Published: April 2024

ABSTRACTThe acquisition of new RNA functions through evolutionary processes would have been essential for the diversification of RNA-based primordial biology and its subsequent transition to modern biology. However, the mechanisms by which RNAs access new functions remain unclear. Do ribozymes need completely new folds to support new but related functions, or is re-optimization of the active site sufficient? What are the roles of neutral and adaptive mutations in evolutionary innovation? Here we address these questions experimentally by focusing on the evolution of substrate specificity in RNA-catalyzed RNA assembly reactions. We use directedin vitroevolution to show that a ligase ribozyme that uses prebiotically relevant 5′-phosphorimidazole-activated substrates can be evolved to catalyze ligation with substrates that are 5′-activated with the biologically relevant triphosphate group. Interestingly, despite catalyzing a related reaction, the new ribozyme folds into a completely new structure and exhibits promiscuity by catalyzing RNA ligation with both triphosphate and phosphorimidazole-activated substrates. Although distinct in sequence and structure, the parent phosphorimidazolide ligase and the evolved triphosphate ligase ribozymes can be connected by a series of point mutations where the intermediate sequences retain at least some ligase activity. The existence of a quasi-neutral pathway between these distinct ligase ribozymes suggests that neutral drift is sufficient to enable the acquisition of new substrate specificity, thereby providing opportunities for subsequent adaptive optimization. The transition from RNA-catalyzed RNA assembly using phosphorimidazole-activated substrates to triphosphate-activated substrates may have set the stage for the later evolution of the protein enzymes that use monomeric triphosphates (NTPs) for RNA synthesis.
RNA tertiary structure and conformational dynamics revealed by BASH MaP
Authors: Oleynikov Maxim , Jaffrey Samie R. 
Published: April 2024

ABSTRACTThe functional effects of an RNA can arise from complex three-dimensional folds known as tertiary structures. However, predicting the tertiary structure of an RNA and whether an RNA adopts distinct tertiary conformations remains challenging. To address this, we developed BASH MaP, a single-molecule dimethyl sulfate (DMS) footprinting method and DAGGER, a computational pipeline, to identify alternative tertiary structures adopted by different molecules of RNA. BASH MaP utilizes potassium borohydride to reveal the chemical accessibility of the N7 position of guanosine, a key mediator of tertiary structures. We used BASH MaP to identify diverse conformational states and dynamics of RNA G-quadruplexes, an important RNA tertiary motif, in vitro and in cells. BASH MaP and DAGGER analysis of the fluorogenic aptamer Spinach reveals that it adopts alternative tertiary conformations which determine its fluorescence states. BASH MaP thus provides an approach for structural analysis of RNA by revealing previously undetectable tertiary structures.
WITHDRAWN: Crosstalk of pathogens with human immune system in airway mucus profiled via machine learning-enhanced data-independent acquisition mass spectrometry
Authors: Pieper Rembert , Krishna Vinod , Thys Kim , Aerssens Jeroen 
Published: April 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to Johnson & Johnson publication policies on online archives of unpublished manuscripts in the biological sciences. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Two species of theEntoloma quadratum–murrayicomplex from Japan,E. kermesinumsp. nov. andE. flavescenssp. nov.
Authors: Sato Hirotoshi , Satomi Otomi , Sugiyama Yoriko 
Published: April 2024

AbstractWe describe two new species,Entoloma. kermesinumsp. nov. andE. flavescenssp. nov., which are confused withE. quadratumandE. murrayi, respectively. We sequenced the large subunit of mitochondrial ribosomal RNA, the nuclear ribosomal internal transcribed spacer region and 22 single-copy genes for 51 specimens ofE. kermesinum,E. flavescens,E. album, and related species. Species boundaries were assessed using the molecular phylogenetics and population genetics approaches. Specimens ofE. kermesinum,E. flavescens, andE. albumformed independent clades, which were phylogenetically distinct from the specimens ofE. quadratumandE. murrayicollected around the type locality (i.e., New England). Although the phylogenetic distance betweenE. flavescensandE. albumwas small, gene flow between them was restricted in areas where they coexisted, suggesting reproductive isolation. Therefore, these five species can be treated as independent species. We found characteristics useful for identifyingE. kermesinumandE. flavescens. In particular,E. kermesinumis characterized by a crimson to brown-red and fibrillose pileus, finely covered by whitish fibrous scales;E. flavescensis characterized by a lemon-yellow to tan and shiny-to-silky pileus. In addition, relatively large basidiospores and clamp connections are diagnostic features of these two species.
Gauge and scalar boson mediated proton decay in a predictive SU(5) GUT model
Authors: Doršner Ilja , Džaferović-Mašić Emina , Fajfer Svjetlana , Saad Shaikh 
Published: April 2024

We assess proton decay signatures in the simplest viable SU(5) model with regard to constraints on parameters governing the Standard Model fermion mass spectrum. Experimental signals for all eight two-body proton decay processes result from exchange of two gauge bosons, a single scalar leptoquark, or their combination. Consequently, it enables us to delve into an in-depth anatomy of proton decay modes and anticipate future signatures. Our findings dictate that observing a proton decay into p→π0e+ indicates gauge boson mediation, with the potential for observation of p→η0e+ mode. Alternatively, if decay is through the p→K+ν¯ process, it is mediated by a scalar leptoquark, possibly allowing the observation of p→π0μ+. Detection of both p→π0e+ and p→K+ν¯ could enhance p→π0μ+ through constructive interference. The model predicts inaccessibility of p→π+ν¯, p→η0μ+, p→K0e+, and p→K0μ+, regardless of the dominant mediation type, in the coming decades. In summary, through a comprehensive analysis of proton decay signals, gauge coupling unification, and fermion masses and mixing, we both accurately and precisely constrain the parameter space of the SU(5) model in question.

Published by the American Physical Society
2024
Scaling and merging macromolecular diffuse scattering with mdx2
Authors: Meisburger Steve P. , Ando Nozomi 
Published: April 2024

Diffuse scattering is a promising method to gain additional insight into protein dynamics from macromolecular crystallography experiments. Bragg intensities yield the average electron density, while the diffuse scattering can be processed to obtain a three-dimensional reciprocal-space map that is further analyzed to determine correlated motion. To make diffuse scattering techniques more accessible, software for data processing called mdx2 has been created that is both convenient to use and simple to extend and modify. mdx2 is written in Python, and it interfaces with DIALS to implement self-contained data-reduction workflows. Data are stored in NeXus format for software interchange and convenient visualization. mdx2 can be run on the command line or imported as a package, for instance to encapsulate a complete workflow in a Jupyter notebook for reproducible computing and education. Here, mdx2 version 1.0 is described, a new release incorporating state-of-the-art techniques for data reduction. The implementation of a complete multi-crystal scaling and merging workflow is described, and the methods are tested using a high-redundancy data set from cubic insulin. It is shown that redundancy can be leveraged during scaling to correct systematic errors and obtain accurate and reproducible measurements of weak diffuse signals.
Global perspectives and methodological innovations in STEM education: a systematic mapping analysis of engineering design-based teacher training
Authors: Shahat Mohamed A. , Al-Balushi Sulaiman M. , Abdullah Shubair , Al-Amri Mohammed 
Published: April 2024

PurposeThis study investigates a novel educational strategy in science, technology, engineering and mathematics (STEM) teaching that integrates the engineering design process (EDP) as a framework. The strategy aims to help teachers explain STEM concepts in a simplified way. We employed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology to enable a systematic review that evaluated the effectiveness of this approach in improving both teaching and learning in STEM subjects.Design/methodology/approachIn order to fulfill the objectives of the review, key data were extracted from each of the 400 articles that were reviewed from three databases: Scopus, ProQuest Central and EBSCO. Two types of analysis were conducted, namely descriptive analysis and literature classification.FindingsThis systematic review analyzed 44 articles on the EDP, focusing on 18 detailed studies mainly from ProQuest, SCOPUS and EBSCO. It revealed a limited focus on gender’s impact on EDP and a trend toward interdisciplinary use and integrated research approaches. The study underscores the need for further exploration of demographic influences and preparation programs in EDP across various disciplines, aiming to inform future research and educational policies.Originality/valueThe study’s value lies in its comprehensive assessment of engineering design (ED) research over the past decade, serving as a key reference point. It highlights progress in the field, consolidates findings and provides insights into the field’s evolution, guiding future research directions in ED.
More than a mere cup of bubble tea: how does perceived luxuriousness affect the intentions to revisit?
Authors: Koay Kian Yeik , Leong Mei Kei 
Published: April 2024

PurposeThis study aims to investigate the influence of perceived luxuriousness on consumers’ revisit intentions via the mediating effects of positive and negative emotions based on the Stimulus-Organism-Response (SOR) model. In this context, “luxuriousness” specifically refers to the richness of furnishings, including the visual allure of aesthetic design and the surrounding cues.Design/methodology/approachA quantitative approach using a survey method is employed to analyse the collected 289 data from consumers of bubble tea. Partial least squares structural equation modelling is chosen as the main analytical approach to examine the research model.FindingsThe results showed that perceived luxuriousness has a significant positive influence on positive emotion and a significant negative influence on negative emotion. Furthermore, positive emotion positively affects revisit intentions, whereas negative emotion negatively affects revisit intentions. Positive emotion mediates the relationship between perceived luxuriousness and revisit intentions, but negative emotion does not.Originality/valueIn terms of theoretical contributions, this study contributes to the SOR model by exploring the influence of perceived luxuriousness on revisit intentions via the mediating effects of emotions in the bubble tea context, which has not been previously examined by past studies. In terms of managerial implications, this study provides insights into how to leverage the element of luxury to encourage consumers to revisit bubble tea stores.