bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach
Authors: Pearson Lesley-Anne , Petit Alain-Pierre , Mendoza Martinez Cesar , Bellany Fiona , Lin De , Niven Sarah , Swift Rachel , Eadsforth Thomas , Fyfe Paul , Paul Marilyn , Postis Vincent , Hu Xiao , Cowling Victoria H. , Gray David W 
Published: October 2024

AbstractThe maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme’s mechanism and a lack of small molecule inhibitors. Following the elucidation of theHsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits. Biophysics, biochemistry and structural biology confirm that both compounds bind competitively with cap and bind effectively toHsRNMT-RAM in the presence of the co-product SAM, with a binding affinity (KD) of approximately 1 μM. This stabilisation of the enzyme-product complex results in uncompetitive inhibition. Finally, we describe the properties of the cap pocket and provided suggestions for further development of the tool compounds.
HBN-EEG: The FAIR implementation of the Healthy Brain Network (HBN) electroencephalography dataset
Authors: Shirazi Seyed Yahya , Franco Alexandre , Hoffmann Maurício Scopel , Esper Nathalia B. , Truong Dung , Delorme Arnaud , Milham Michael P. , Makeig Scott 
Published: October 2024

AbstractThe Child Mind Institute (CMI) Healthy Brain Network (HBN) project has recorded phenotypic, behavioral, and neuroimaging data from ∼5,000 children and young adults between the ages of 5 and 21. Here, we present HBN-EEG, the “analysis-ready” data from its high-density (128-channel) electroencephalographic (EEG) recording sessions formatted as Brain Imaging Data Structure (BIDS) datasets. HBN-EEG also includes behavioral and task-condition events annotated using Hierarchical Event Descriptors (HED), making the datasets analysis-ready for many purposes without ‘forensic’ search for unreported details. We also ensured data consistency and event integrity and marked inconsistencies. HBN-EEG sessions include six tasks, three with no participant behavioral input (passive tasks) and three including button press responses following task instructions (active tasks). Openly available participant information includes age, gender, and four psychopathology dimensions (internalizing, externalizing, attention, and p-factor) derived from a bifactor model of questionnaire data. Currently, HBN-EEG data from more than 2,600 participants is freely available on NEMAR (nemar.org) and OpenNeuro in the form of nine dataset releases, with further dataset releases to follow.
Loss of pleiotropic regulatory functions inTannin1, the sorghum ortholog of Arabidopsis master regulatorTTG1
Authors: Schuh Anthony , Morris Geoffrey P. 
Published: October 2024

ABSTRACTTranscriptional master regulators are often targeted to improve plant traits, but antagonistic pleiotropic effects of these regulators can hamper this approach. The Myb-bHLH-WDR (MBW) complex is a broadly-conserved transcriptional regulator affecting pigmentation, biotic stress resistance, and abiotic stress tolerance. We investigated the function of sorghum grain pigmentation regulatorTannin1, the ortholog of Arabidopsis pleiotropic WD40 regulatorTTG1, to test for conserved pleiotropic regulatory effects and to better understand the evolution of the MBW complex in Poaceae. We characterized genome-wide differential expression of leaf tissue using RNA sequencing in near-isogenic lines (NILs) that contrasted wildtypeTan1and loss-of-functiontan1-balleles, under optimal temperature and chilling stress. Notably, Gene Ontology analyses revealed no pathways with differential expression betweenTan1andtan1-bNILs, suggesting that, in contrast to ArabidopsisTTG1, Tannin1has no pleiotropic regulatory role in leaves. Further, NILs had no visible difference in anthocyanin pigmentation, and no genes with known or expected function in flavonoid synthesis were differentially expressed. Genome-wide, only 18 total genes were differentially expressed between NILs, with six of these genes located inside the NIL introgression region, an observation most parsimoniously explained bycis-regulatory effects unrelated toTannin1regulation. Comparing our findings with known function ofTTG1orthologs in maize, rice, and Arabidopsis, we conclude that pleiotropic regulatory function in leaf tissue was likely lost in panicoid grass evolution before the sorghum-maize split. These findings inform future molecular breeding of MBW regulated traits and highlight the benefit of subfunctionalization to relieve pleiotropic constraints.
STAMP: Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging
Authors: Pitino Emanuele , Pascual-Reguant Anna , Segato-Dezem Felipe , Wise Kellie , Salvador-Martinez Irepan , Crowell Helena Lucia , Courtois Elise , Flynn William F. , Sivajothi Santhosh , Soja Emily , Ruiz Sara , Caratù Ginevra , Sullivan Adrienne E. , Mora Roldan German Atzin , Dredge B. Kate , Marção Maycon , Liu Yutian , Chasteen Hannah , Mohenska Monika , Polo José , Nieto Juan C. , Plummer Jasmine , Heyn Holger , Martelotto Luciano 
Published: October 2024

AbstractWe introduce Single-Cell Transcriptomics Analysis and Multimodal Profiling (STAMP), a scalable profiling approach of individual cells. Leveraging transcriptomics and proteomics imaging platforms, STAMP eliminates sequencing costs, to enable single-cell genomics from hundreds to millions of cells at an unprecedented low cost. Stamping cells in suspension onto imaging slides, STAMP supports single-modal (RNA or protein) and multimodal (RNA and protein) profiling and flexible, ultra-high-throughput formats. STAMP allows the analysis of a single or multiple samples within the same experiment, enhancing experimental flexibility, throughput and scale. We tested STAMP with diverse sample types, including peripheral blood mononuclear cells (PBMCs), dissociated cancer cells and differentiated embryonic stem cell cultures, as well as whole cells and nuclei. Combining RNA and protein profiling, we applied immuno-phenotyping of millions of blood cells simultaneously. We also used STAMP to identify ultra-rare cell populations, simulating clinical applications to identify circulating tumor cells (CTCs). Performingin vitrodifferentiation studies, we further showed its potential for large-scale perturbation studies. Together, STAMP establishes a new standard for cost-effective, scalable single-cell analysis. Without the need for sequencing, STAMP makes high-resolution profiling more affordable and accessible. Designed to meet the needs of research labs, diagnostic cores and pharmaceutical companies, STAMP holds the promise to transform our capacity to map human biology, diagnose diseases and drug discovery.
Detection of titanium nanoparticles in human, animal and infant formula milk
Authors: Rivard Camille , Djebrani-Oussedik Nouzha , Cloix Romane , Hue-Beauvais Cathy , Kuszla Nicolas , Ivanova Elitsa , Simon Marie , Dufour Adrien , Launay Frédéric , Gazeau Florence , Acloque Hervé , Parat Sophie , Poupon Joël , Burtey Anne 
Published: October 2024

AbstractThe sustainability of mammals on Earth relies on milk. During lactation, maternal exposure to pollutants like metal nanoparticles (NPs) can affect offspring development and survival. Despite being banned from food applications in Europe due suspected toxicity, titanium dioxide (TiO2) NPs are still massively manufactured for countless other uses. While contamination of ecosystems is well documented, contamination of mammals remains underexplored. Here, we used synchrotron X-ray fluorescence and single particle inductively coupled plasma mass spectrometry to analyse human, animal, and infant formula milk. Titanium containing micro- and nano-particles were detected in all samples, regardless of the species, location, and processing. We identified varying concentrations, sizes, and combinations of rutile and anatase TiO2, ilmenite FeTiO3and possibly titanite CaTiSiO5or pseudobrookite Fe2TiO5. These findings suggest that milk serves as a carrier for titanium-containing nanomaterials to expose newborns on a daily basis until weaning.
Differential effects of conventional transcranial direct current stimulation (tDCS) and high-definition transcranial direct current stimulation (HD-tDCS) of the cerebellum on offset analgesia
Authors: O’Connor Niamh , Ashe Hannah , Wragan Max , O’Flaherty Ruairí , Deevy-Gray Eoin , Witney Alice G. 
Published: October 2024

AbstractBackgroundOffset analgesia (OA) describes the large decrease in perceived pain in response to a minor decrease in applied painful thermal stimulus. Here non-invasive brain stimulation (NIBS) is used to modulate the cerebellum, since the cerebellum is known to signal sensory prediction errors and is implicated in pain processing.MethodsAn OA protocol individualized to heat pain threshold (HPT) was applied via TSA-II (Medoc, Israel). NIBS interventions were applied prior to OA. Cathodal cerebellar transcranial direct current stimulation (tDCS) and high-definition (4X1) transcranial direct current stimulation (HD-tDCS) were applied to 46 healthy participants within a sham controlled repeated measures design to examine whether diffuse or focal stimulation differentially modulates OA.ResultsOA induced hypoalgesia was robust, with 90% of responses showing a drop in perceived pain (δVAS) > 10 following the 1°C fall in temperature. This OA response was augmented following a protocol with sham and focal cathodal cerebellar stimulation on four OA parameters (OAlatency, VASminimum, VASmeanand VAS2ndmax) relative to pre-stimulation. This effect was differential to the protocol with sham and conventional tDCS where two OA metrics altered (OAduration, VAS2ndmax).ConclusionOA enhancement via cathodal cerebellar NIBS may involve both a placebo effect and sustaining a noxious sensory prediction error. Understanding how the cerebellum is involved in OA could enhance therapies for pain patients.
DYRK1A kinase triplication is the major cause of Otitis Media in Down Syndrome
Authors: Tateossian Hilda , Southern Amy , Vikhe Pratik , Lana-Elola Eva , Watson-Scales Sheona , Gibbins Dorota , Williams Debbie , Purnell Thomas , Mburu Philomena , Parker Andrew , Norris Dominic P , Santos-Cortez Regie Lyn P , Herrmann Brian W , Wells Sara , Lad Heena V , Fisher Elizabeth MC , Tybulewicz Victor LJ , Brown Steve DM 
Published: October 2024

AbstractDown syndrome (DS), which arises from trisomy of the whole or part of chromosome 21 (Hsa21), is one of the most common genetic abnormalities in humans. DS manifests as a broad spectrum of phenotypic features, including hearing loss due to otitis media with effusion (OME), affecting around 50% of children with DS. We employed a panel of mouse models of DS comprising a nested series of duplications covering the regions of the mouse genome syntenic to Hsa21 in order to define the loci involved with OME in DS. We identified a major locus on mouse chromosome 16, containing only 12 genes, that causes OME. Within this region we demonstrate that normalizing the gene dosage ofDyrk1arestored the wild-type phenotype. Investigation of downstream pathways of DYRK1A uncovered a number of pathological mechanisms whereby DYRK1A triplication leads to middle ear inflammation and vascular leak. These include cross-talk of DYRK1A and TGFβ signaling and its impact on proinflammatory cytokines IL-6 and IL-17, as well as raised VEGF levels in the middle ear accompanied by increasedHif1a. We conclude that DYRK1A is a potential therapeutic target for OME in children with DS.
A Targeted Reference Database for Improved Analysis of Environmental 16S rRNA Oxford Nanopore Sequencing Data
Authors: Philip Melcy , Nilsen Tonje , Majaneva Sanna , Pettersen Ragnhild , Stokkan Morten , Ray Jessica Louise , Keeley Nigel , Rudi Knut , Snipen Lars-Gustav 
Published: October 2024

AbstractThe Oxford Nanopore Technologies (ONT) sequencing platform is compact and efficient, making it suitable for rapid biodiversity assessments in remote areas. Despite its long reads, ONT has a higher error rate compared to other platforms, necessitating high-quality reference databases for accurate taxonomic assignments. However, the absence of targeted databases for underexplored habitats, such as the seafloor, limits ONT’s broader applicability for exploratory analysis.To address this, we propose an approach for building environmentally-targeted databases to improve 16S rRNA gene (16S) analysis using Oxford Nanopore Technologies (ONT), using seafloor sediment samples from the Norwegian coast as an example. We started by using Illumina short-read data to create a database of full-length or near full-length 16S sequences from seafloor samples. Initially, amplicons are mapped to the SILVA database, with matches added to our database. Unmatched amplicons are reconstructed using METASEED and Barrnap methodologies with amplicon and metagenome data. Finally, if the previous strategies did not succeed, we included the short-read sequences in the database. This resulted in AQUAeD-DB, which contains 14 545 16S sequences clustered at 95% identity. Comparative database analysis reveal that AQUAeD-DB provides consistent results for both Illumina and Nanopore read assignments (median correlation coefficient: 0.50), whereas a standard database showed a substantially weaker correlation. These findings also emphasize its potential to recognize both high and low-abundance taxa, which could be key indicators in environmental studies. This work highlights the necessity of targeted databases for environmental analysis, especially for ONT-based studies, and lays foundations for future extension of the database.
Same bi-directional modulation of contrast appearance for voluntary presaccadic attention and involuntary exogenous attention
Authors: Zhang Tianyu , Cai Yongchun 
Published: October 2024

AbstractDifferent types of attention alter subjective visual perception in fundamentally distinct ways. Previous studies have focused on covert attention without concurrent eye movements, showing that covert exogenous (involuntary) attention enhances contrast appearance of low-contrast stimuli while diminishing that of high-contrast stimuli, whereas covert endogenous (voluntary) attention uniformly enhances contrast appearance. However, the attentional effect preceding saccadic eye movements, a critical component of natural vision, remain understudied. Here, we found that when participants voluntarily initiated saccades, presaccadic attention enhanced the appearance of low-contrast stimuli while attenuating the appearance of high-contrast stimuli (Experiment 1,N= 29 adults). This pattern is surprisingly similar to exogenous attention but distinct from endogenous attention. Notably, the presaccadic attentional attenuation effect accumulated gradually during saccade preparation and remained positively correlated with the exogenous attentional effect (Experiment 2,N= 24 adults). These findings suggest a shared mechanism between presaccadic and exogenous attention in shaping visual perception.
Improved maximum growth rate prediction from microbial genomes by integrating phylogenetic information
Authors: Xu Liang , Zakem Emily , Weissman JL 
Published: October 2024

AbstractMicrobial maximum growth rates vary widely across species and are key parameters for ecosystem modeling. Measuring these rates is challenging, but genomic features like codon usage statistics provide useful signals for predicting growth rates for as-yet uncultivated organisms, though current predictors often show high variance. To improve accuracy, we integrate phylogenetic signals, leveraging the evolutionary relationships among species to refine trait predictions. We presentPhydon, which combines codon statistics and phylogenetic information to enhance the precision of maximum growth rate estimates, especially when a close relative with a known growth rate is available. We construct the largest and most taxonomically broad database of temperature-corrected growth rate estimates for 111,349 microbial species. The results reveal a bimodal distribution of maximum growth rates, resolving distinct groups of fast and slow growers. Our hybrid approach advances the accuracy of genome-based growth rate predictions and presents a new framework for accurate genome-based trait prediction.
Data-driven insights into the association between oxidative stress and calcium-regulating proteins in cardiovascular disease
Authors: Panday Namuna , Sigdel Dibakar , Adam Irsyad , Ramirez Joseph , Verma Aarushi , Eranki Anirudh , Wang Wei , Wang Ding , Ping Peipei 
Published: October 2024

AbstractA growing body of biomedical literature suggests a bidirectional regulatory relationship between cardiac calcium (Ca2+)-regulating proteins and reactive oxygen species (ROS), which is integral to the pathogenesis of various cardiac disorders via oxidative stress signaling. To address the challenge of finding hidden connections within the growing volume of biomedical research, we developed a data science pipeline for efficient data extraction, transformation, and loading. Employing the CaseOLAP (Context-Aware Semantic Analytic Processing) algorithm, our pipeline quantifies interactions between 128 human cardiomyocyte Ca2+-regulating proteins and eight cardiovascular disease (CVD) categories. Our machine learning analysis of CaseOLAP scores reveals that the molecular interfaces of Ca2+-regulating proteins uniquely associate with cardiac arrhythmias and diseases of the cardiac conduction system, distinguishing them from other CVDs. Additionally, a knowledge graph analysis identified 59 of the 128 Ca2+-regulating proteins as involved in OS-related cardiac diseases, with cardiomyopathy emerging as the predominant category. By leveraging a link prediction algorithm, our research illuminates interactions between Ca2+-regulating proteins, OS, and CVDs. The insights gained from our study provide a deeper understanding of the molecular interplay between cardiac ROS and Ca2+-regulating proteins in the context of CVDs. Such understanding is essential for the innovation and development of targeted therapeutic strategies.
An integrated polygenic score stratifies risk of peripheral artery disease and adverse limb events in ancestrally diverse cohorts
Authors: Flores Alyssa M. , Ruan Yunfeng , Misra Anika , Selvaraj Margaret S. , Bellomo Tiffany R. , Nakao Tetsushi , Rosenfield Kenneth , Eagleton Matthew , Hornsby Whitney , Patel Aniruddh P. , Natarajan Pradeep 
Published: October 2024

AbstractBackground and AimsPeripheral artery disease (PAD) is a heritable atherosclerotic condition that is underdiagnosed and undertreated. With growing knowledge of the genetic basis for PAD and related risk factors, this study sought to construct a new polygenic score for PAD (GPSPAD).MethodsGPSPADwas constructed by integrating multi-ancestry summary statistics for PAD and related traits. GPSPADwas trained in a UK Biobank dataset of 96,239 individuals and validated in a holdout UK Biobank dataset (N=304,294) and All of Us (AoU; N=237,173) and Mass General Brigham Biobank (MGBB, N=37,017).ResultsGPSPADwas associated with an OR-per SD increase of 1.64 in the UK Biobank dataset (95% CI 1.60-1.68). Compared to previously published PAD polygenic scores, GPSPADwas more strongly associated with PAD in AoU and MGBB, including enhanced transferability to non-European subgroups. GPSPADimproved discrimination of incident PAD (1¢C-statistic 0.030) that was nearly equivalent to the additive performances of diabetes (1¢C-statistic 0.029) and smoking (1¢C-statistic 0.034). GPSPADwas associated with reduced ankle-brachial index in the MGBB with the top 8% of individuals having a mean ABI<0.90 when assessed. Among individuals with prevalent PAD, GPSPADconsistently identified individuals at high MALE-risk in the UK Biobank (HR 1.48; 95% CI 1.24-1.77), MGBB, (HR 1.34; 95% CI 1.12-1.60), and AoU (HR 1.33; 95% CI 1.12-1.58).ConclusionsAn integrated, multi-ancestry polygenic score for PAD predicts disease and adverse limb outcomes in three diverse cohorts. Incorporating polygenic risk into PAD care has the potential to guide screening and tailor management to prevent MALE.
All-loop geometry for four-point correlation functions
Authors: He Song , Huang Yu-tin , Kuo Chia-Kai 
Published: October 2024

In this letter, we consider a positive geometry conjectured to encode the loop integrand of four-point stress-energy correlators in planar N=4 super Yang-Mills. Beginning with four lines in twistor space, we characterize a positive subspace to which an ℓ-loop geometry is attached. The loop geometry then consists of ℓ lines in twistor space satisfying positivity conditions among themselves and with respect to the base. Consequently, the can be viewed as fibration over a . The fibration naturally dissects the base into chambers, in which the degree-4ℓ loop form is unique and distinct for each chamber. Interestingly, up to three loops, the chambers are simply organized by the six ordering of x1,22x3,42, x1,42x2,32, and x1,32x2,42. We explicitly verify our conjecture by computing the loop-forms in terms of a basis of planar conformal integrals up to ℓ=3, which indeed yield correct loop integrands for the four-point correlator.

Published by the American Physical Society
2024
Dinuclear zinc(II) acetate complexes derived from N,N′,S-tridentate Schiff bases: synthesis, structural study and Hirshfeld surface analysis
Authors: Anaya-Avila Odalys , Muñoz-Granados Oscar , Andrade-López Noemí , Alvarado-Rodríguez José G. , Martínez-Otero Diego 
Published: October 2024

Three dinuclear zinc(II) acetate complexes of the general formula [Zn{L

n

}(AcO)]2, namely, di-μ-acetato-κ4
O:O′-bis[({2-[(pyridin-2-ylmethylidene)amino]phenyl}sulfanido-κ3
N,N′,S)zinc(II)], [Zn2(C12H9N2S)2(C2H3O2)2] (n = 1), 4, μ-acetato-1:2κ2
O:O′-acetato-2κO-[μ-(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κS:2κ3
N,N′,S][(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κ3
N,N′,S]dizinc(II), [Zn2(C13H11N2S)2(C2H3O2)2] (n = 2), 5, and μ-acetato-1:2κ2
O:O′-acetato-2κO-[μ-(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κS:2κ3
N,N′,S][(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κ3
N,N′,S]dizinc(II)–bis(2-aminophenyl) disulfide (2/1), [Zn2(C18H13N2S)2(C2H3O2)2]·0.5C12H12N2S2 (n = 3), 6·0.5(2-APS)2, were obtained from the reaction of 2-R-(pyridin-2-yl)benzothiazoline precursors (R = H, 1; R = Me, 2; R = Ph, 3) with zinc acetate dihydrate in a 1:1 ratio. All the complexes crystallized as dinuclear species and complex 6 cocrystallized with one molecule of bis(2-aminophenyl) disulfide (2-APS)2. The anionic Schiff base ligands {L

n

}− displayed a κ2
N,κS-tridentate coordination mode with the formation of two five-membered chelate rings. In 4, 5 and 6·0.5(2-APS)2, both ZnII ions are pentacoordinated and the coordination sphere of 4 was different with respect to those in 5 and 6·0.5(2-APS)2. For 4, the X-ray diffraction study showed a dinuclear complex containing two bridging acetate ligands linked to both ZnII ions. For 5 and 6·0.5(2-APS)2, the dinuclear complexes displayed one bridging acetate ligand linked to both ZnII ions, where the first ZnII ion includes a dative bond with one S atom from an adjacent anionic Schiff base {L

n

}−, while the second ZnII ion is coordinated to one terminal acetate ligand. In each dinuclear complex, the geometry is the same for both ZnII metal centres. The local geometry of the ZnII cation in 4 is halfway between trigonal bipyramidal and square pyramidal local geometries; in 5 and 6, the local geometries are described as distorted square pyramidal. Hirshfeld surface analysis of 5 and 6 showed the predominance of H...H interactions, as well as the contribution of C—H...C, C—H...O and C—H...S noncovalent interactions to the cohesion of the crystalline network of the ZnII complexes.