bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACE2 mimetic antibody potently neutralizes all SARS-CoV-2 variants and fully protects in XBB.1.5 challenged monkeys
Authors: Fenwick Craig , Turelli Priscilla , Duhoo Yoan , Lau Kelvin , Herate Cécile , Marlin Romain , Lamrayah Myriam , Campos Jérémy , Esteves-Leuenberger Line , Farina Alex , Raclot Charlène , Genet Vanessa , Fiscalini Flurin , Cesborn Julien , Perez Laurent , Dereuddre-Bosquet Nathalie , Contreras Vanessa , Lheureux Kyllian , Relouzat Francis , Abdelnabi Rana , Foo Caroline S. , Neyts Johan , Leyssen Pieter , Lévy Yves , Pojer Florence , Stahlberg Henning , Le Grand Roger , Trono Didier , Pantaleo Giuseppe 
Published: July 2023

AbstractThe rapid evolution of SARS-CoV-2 to variants with improved transmission efficiency and reduced sensitivity to vaccine-induced humoral immunity has abolished the protective effect of licensed therapeutic human monoclonal antibodies (mAbs). To fill this unmet medical need and protect vulnerable patient populations, we isolated the P4J15 mAb from a previously infected, vaccinated donor, with <20 ng/ml neutralizing activity against all Omicron variants including the latest XBB.2.3 and EG.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. Although SARS-CoV-2 mutants escaping neutralization by P4J15 were selectedin vitro, these displayed lower infectivity, poor binding to ACE2, and the corresponding ‘escape’ mutations are accordingly rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, we show that P4J15 confers complete prophylactic protection. We conclude that the P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug.
Multi-omics analyses from a single sample: Prior metabolite extraction does not alter the 16S rRNA-based characterization of prokaryotic community in a diversity of sample types
Authors: Duperron Sébastien , Foucault Pierre , Duval Charlotte , Goto Midoli , Gallet Alison , Colas Simon , Marie Benjamin 
Published: July 2023

AbstractMassive sequencing of the 16S rRNA gene has become a standard first step to describe and compare microbial communities from various samples. Parallel analysis of high numbers of samples makes it relevant to the statistical testing of the influence of natural or experimental factors and variables. However, these descriptions fail to document changes in community or ecosystem functioning. Non-targeted metabolomics are a suitable tool to bridge this gap, yet extractions protocols are different. In this study, prokaryotic community compositions are documented by 16S rRNA sequencing after direct DNA extraction, or after metabolites extraction followed by DNA extraction. Results obtained using the V3-V4 region on non-axenic cultures of cyanobacteria, lake water column, biofilm, gut of wild and lab-reared fish, indicate that prior extraction of metabolites does not influence the obtained image of prokaryotic communities. This validates sequential extraction of metabolites followed by DNA as a way to combine 16S rRNA sequencing with metabolome characterization from a single sample. This approach has the potential to complement community structure characterization with a proxy of their functioning, without the uncertainties associated with the use of separate samples.
The HCM – Linked Mutation Arg92Leu in TNNT2 Allosterically Alters the cTnC – cTnI Interface and Disrupts the PKA-mediated Regulation of Myofilament Relaxation
Authors: Lynn Melissa L. , Jimenez Jesus , Castillo Romi L. , Klass Matthew M. , Vasquez Catherine , Baldo Anthony , Gibson Cyonna , Murphy Anne M. , Tardiff Jil C. 
Published: July 2023

ABSTRACTBackgroundImpaired left ventricular relaxation, high filling pressures, and dysregulation of Ca2+homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort which suggests potential involvement of myofilament regulators of relaxation. Yet, a molecular level understanding of mechanism(s) at the level of the myofilament is lacking. We hypothesized that mutation-specific, allosterically mediated, changes to the cardiac troponin C-cardiac troponin I (cTnC-cTnI) interface can account for the development of early-onset diastolic dysfunction via decreased PKA accessibility to cTnI.MethodsHCM mutations R92L-cTnT (Arg92Leu) and Δ160E-cTnT (Glu160 deletion) were studiedin vivo,in vitro,andin silicovia 2D echocardiography, western blotting,ex vivohemodynamics, stopped-flow kinetics, time resolved fluorescence resonance energy transfer (TR-FRET), and molecular dynamics simulations.ResultsThe HCM-causative mutations R92L-cTnT and Δ160E-cTnT result in different time-of-onset of diastolic dysfunction. R92L-cTnT demonstrated early-onset diastolic dysfunction accompanied by a localized decrease in phosphorylation of cTnI. Constitutive phosphorylation of cTnI (cTnI-D23D24) was sufficient to recover diastolic function to Non-Tg levels only for R92L-cTnT. Mutation-specific changes in Ca2+dissociation rates associated with R92L-cTnT reconstituted with cTnI-D23D24led us to investigate potential involvement of structural changes in the cTnC-cTnI interface as an explanation for these observations. We probed the interface via TR-FRET revealing a repositioning of the N-terminus of cTnI, closer to cTnC, and concomitant decreases in distance distributions at sites flanking the PKA consensus sequence. Implementing TR-FRET distances as constraints into our atomistic model identified additional electrostatic interactions at the consensus sequence.ConclusionThese data indicate that the early diastolic dysfunction observed in a subset of HCM is likely attributable to structural changes at the cTnC-cTnI interface that impair accessibility of PKA thereby blunting β-adrenergic responsiveness and identifying a potential molecular target for therapeutic intervention.
Identification of endothelial-to-mesenchymal transition gene signatures in single-cell transcriptomics of human atherosclerotic tissue
Authors: Slenders Lotte , Wesseling Marian , Boltjes Arjan , Kapteijn Daniek M.C. , Depuydt Marie A.C. , Prange Koen , van den Dungen Noortje A.M. , Benavente Ernest Diez , P.V. de Kleijn Dominique , de Borst Gert J. , den Ruijter Hester M. , Owens Gary K. , Mokry Michal , Pasterkamp Gerard 
Published: July 2023

AbstractRationaleEndothelial cells can differentiate into mesenchymal-like cells via endothelial to mesenchymal transition (EndoMT). In murine models, cell transitions of EndoMT have been assessed with lineage tracing techniques. Knowledge on molecular mechanisms of EndoMT in human vascular lesions is scarce as studies in human atherosclerosis are limited by observational study designs such as histo-pathological studies.ObjectiveWe aim to identify a human EndoMT gene expression signature by combining experimentally inducedin vitroEndoMT with lineage-traced pathways from atherosclerotic mice and extrapolate this to human plaque scRNA-seq data.Methods and resultsFirst, we stimulated human coronary artery endothelial cells (HCAEC) with TNFα and TFGβ to trigger EndoMT. We executed transcriptomic analyses and defined multiple temporal patterns of gene expression changes during EndoMT. We used Cdh5-CreERT2Rosa-eYFP apoE-/-lineage traced mouse scRNA-seq data to demonstrate that the temporalin vitrogene expression changes are reflected in EndoMT trajectories in mice plaque tissue. Finally, we constructed three candidate EndoMT lineages across multiple subpopulations of ECs and SMCs in human carotid scRNA-seq data (n=46). We examined gene expression over the course of these lineages and identified 73 markers for the presence of EndoMT such asNRG1andDEPP1.ConclusionThis study reveals the gene expression profile of EndoMT trajectories in human atherosclerotic plaques by combining RNA-seq data fromin vitromodels with single-cell transcriptomic datasets. Our gene expression atlas of EndoMT in atherosclerosis could serve as a reference for future studies, providing novel inroads to study atherosclerotic mechanisms for the development of novel therapies.
Diffusion time-related structure-function coupling reveals differential association with inter-individual variations in body mass index
Authors: Namgung Jong Young , Park Yeong Jun , Park Yunseo , Kim Chae Yeon , Park Bo-yong 
Published: July 2023

ABSTRACTBody mass index (BMI) is an indicator of obesity, and recent neuroimaging studies have demonstrated inter-individual variations in BMI to be associated with altered brain structure and function. However, how the structure-function correspondence is altered according to BMI is under-investigated. In this study, we combined structural and functional connectivity using Riemannian optimization with varying diffusion time parameters and assessed their association with BMI. First, we simulated functional connectivity from structural connectivity and generated low-dimensional principal gradients of the simulated functional connectivity across diffusion times, where low and high diffusion times indirectly reflected mono- and polysynaptic communication. We found the most apparent cortical hierarchical organization differentiating between low-level sensory and higher-order transmodal regions in the middle of the diffusion time, indicating that the hierarchical organization of the brain may reflect the intermediate mechanisms of mono- and polysynaptic communications. Associations between the simulated gradients and BMI revealed the strongest relationship when the hierarchical structure was most evident. Moreover, the functional gradient-BMI association map showed significant correlations with the cytoarchitectonic measures of the microstructural gradient and moment features, indicating that BMI-related functional connectome alterations were remarkable in higher-order cognitive control-related brain regions. Finally, transcriptomic association analysis provided potential biological underpinnings, specifying gene enrichment in the striatum, hypothalamus, and cortical cells. Our findings provide evidence that structure-function correspondence is strongly coupled with BMI when hierarchical organization is most apparent, and the associations are related to the multiscale properties of the brain, leading to an advanced understanding of the neural mechanisms related to BMI.
Poisson representation: a bridge between discrete and continuous models of stochastic gene regulatory networks
Authors: Wang Xinyu , Li Youming , Jia Chen 
Published: July 2023

AbstractStochastic gene expression dynamics can be modeled either discretely or continuously. Previous studies have shown that the mRNA or protein number distributions of some simple discrete and continuous gene expression models are related by Gardiner’s Poisson representation. Here we systematically investigate the Poisson representation in complex stochastic gene regulatory networks. We show that when the gene of interest is unregulated, the discrete and continuous descriptions of stochastic gene expression are always related by the Poisson representation, no matter how complex the model is. In addition, using a simple counterexample, we find that the Poisson representation in general fails to link the two descriptions when the gene is regulated. However, for a general stochastic gene regulatory network, we demonstrate that the discrete and continuous models are approximately related by the Poisson representation in the limit of large protein numbers. These theoretical results are further applied to analytically solve many complex gene expression models whose exact distributions are previously unknown.
IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota
Authors: Röwekamp Ivo , Maschirow Laura , Rabes Anne , Vernengo Facundo Fiocca , Heinz Gitta Anne , Mashreghi Mir-Farzin , Caesar Sandra , Milek Miha , Fagundes Fonseca Anna Carolina , Wienhold Sandra-Maria , Nouailles Geraldine , Yao Ling , Bruder Dunja , Boehme Julia D. , Puzianowska-Kuznicka Monika , Beule Dieter , Witzenrath Martin ,   CAPNETZ Study Group, Löhning Max , Heimesaat Markus M. , Klose Christoph S.N. , Diefenbach Andreas , Opitz Bastian 
Published: July 2023

ABSTRACTIL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant toStreptococcus pneumoniaelung infection than wild-type animals, and that single nucleotide polymorphisms inIL33andIL1RL1were associated with pneumococcal pneumonia in humans. The effect of IL-33 onS. pneumoniaeinfection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33’s influence on antibacterial defense was dependent on housing conditions of the mice, and mediated by the modulatory effect of IL-33 on the microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We identify a mechanism, dependent on both genetic and environmental factors, that impacts the efficacy of antibacterial immune defense and thus susceptibility to pneumonia.SIGNIFICANCE STATEMENTLower respiratory tract infections are the fifth leading cause of death. Here, we describe a mechanism influenced by genetic and environmental factors that affects the efficacy of pulmonary antibacterial immune responses. We show that IL-33 controls antibacterial defense by regulating the production of IL-22, a cytokine with known functions in antimicrobial immunity in lungs. The effect of IL-33 on IL-22-dependent defense was influenced by the hygienic status of the mice and mediated by IL-33’s modulatory effect on the animal microbiota. In addition, genetic variation in genes involved in IL-33 signaling was associated with bacterial pneumonia in humans. Our findings may be important for our understanding of the factors influencing predisposition to lower respiratory tract infections.
Geographic isolation enables recurrent pollinator shifts despite hybridisation in the Cape’s hyperdiverse heathers
Authors: Musker Seth D. , Pirie Michael D. , Nürk Nicolai M. 
Published: July 2023

SummaryDeciphering the ecological and geographic factors that influence the dynamics of population divergence can aid in understanding why some groups of organisms diversify more prolifically than others. One such diverse group is the heathers (Erica, Ericaceae), whose exceptional species richness in the Cape Floristic Region is enigmatic. Here, we studyErica abietina, a small but highly variable species complex with four described subspecies differing in geographic range, habitat, and floral characters associated with pollination. To understand the factors and forces that shaped its evolution, we evaluate the status of the subspecies and test for hybridisation, introgression, pollinator-driven divergence, and geographic population structure using genotyping-by-sequencing on samples across the entire distribution. We find that the four subspecies form variably distinct genetic groups, however, the most widespread subspecies exhibits cryptic diversity comprising two independent lineages that are geographically isolated and occur on different soil types. Phylogenetic results suggest that shifts between bird- and insect-pollination syndromes have occurred twice independently, with accompanying genetic divergence. However, for one pair of genetically distinct populations (FST≈0.06) with different pollinators we uncover several individuals of hybrid origin at a site where they occur sympatrically. Together, these results suggest that floral differentiation driven by divergent selection acts in concert with geographic isolation to maintain reproductive isolation. Finally, we show that a reticulate history involving “ghost” introgression best explains the group’s evolution. Our results reveal a highly dynamic system whose diversity has been shaped by a variety of interacting forces, and we suggest that such systems are likely to have contributed substantially to the diversity ofEricaand the Cape flora in general.
The neural and computational architecture of feedback dynamics in mouse cortex during stimulus report
Authors: Ciceri Simone , Lohuis Matthijs Noude , Rottschäfer Vivi , Pennartz Cyriel MA , Avitabile Daniele , van Gaal Simon , Olcese Umberto 
Published: July 2023

AbstractConscious reportability of visual input is associated with a bimodal neural response in primary visual cortex (V1): an early-latency response coupled to stimulus features and a late-latency response coupled to stimulus report or detection. This late wave of activity, central to major theories of consciousness, is thought to be driven by prefrontal cortex (PFC), responsible for “igniting” it. Here we analyzed two electrophysiological studies in mice performing different stimulus detection tasks, and characterize neural activity profiles in three key cortical regions: V1, posterior parietal cortex (PPC) and PFC. We then developed a minimal network model, constrained by known connectivity between these regions, reproducing the spatio-temporal propagation of visual-and report-related activity. Remarkably, while PFC was indeed necessary to generate report-related activity in V1, this occurred only through the mediation of PPC. PPC, and not PFC, had the final veto in enabling the report-related late wave of V1 activity.
Examining the role of social media influencers in service failure and recovery strategies: an empirical investigation of millennials' views
Authors: Ozuem Wilson , Willis Michelle , Ranfagni Silvia , Howell Kerry , Rovai Serena 
Published: July 2023

PurposePrior research has advanced several explanations for social media influencers' (SMIs’) success in the burgeoning computer-mediated marketing environments but leaves one key topic unexplored: the moderating role of SMIs in service failure and recovery strategies.Design/methodology/approachDrawing on a social constructivist perspective and an inductive approach, 59 in-depth interviews were conducted with millennials from three European countries (Italy, France and the United Kingdom). Building on social influence theory and commitment-trust theory, this study conceptualises four distinct pathways unifying SMIs' efforts in the service failure recovery process.FindingsThe emergent model illustrates how source credibility and message content moderate service failure severity and speed of recovery. The insights gained from this study model contribute to research on the pivotal uniqueness of SMIs in service failure recovery processes and offer practical explanations of variations in the implementation of influencer marketing. This study examines a perspective of SMIs that considers the cycle of their influence on customers through service failure and recovery.Originality/valueThe study suggests that negative reactions towards service failure and recovery are reduced if customers have a relationship with influencers prior to the service failure and recovery compared with the reactions of customers who do not have a relationship with the influencer.
Colloquial Persian: Towards a New Rise of Simple Verbs?1
Authors: Pastor Dorian , Korn Agnes , Rammer Christian 
Published: July 2023

AbstractFor the formation of new verbs, Persian very productively employs complex predicates, while the derivation of simple verbs has been held to be marginal or even inexistent. We use data from internet fora, blogs, and messaging services to argue that the derivation of simple verbs from nominals is a productive process at least among speakers of colloquial Persian who actively use online media. Two acceptability tests of seven verbs and two ‘placebo verbs’ conducted among 58 participants produced more than 7,000 gradings. They show that such verbs are surprisingly well accepted, with statistically significant differences depending on age, gender, region, TAM form, and the individual verbs. Some of these results seem quite straightforward (e.g., acceptance declining with age), others rather not (for instance, the present and past progressive is very well accepted). The results run counter to the assumption that a gradual substitution of synthetic structures (simple verbs) by analytical ones (complex predicates) is a unidirectional process.
Efficacy of mixed diclofenac solutions against root canal biofilms
Authors: Ferrer‐Luque Carmen Maria , Solana Carmen , Aguado Beatriz , Baca Pilar , Arias‐Moliz María Teresa , Ruiz‐Linares Matilde 
Published: July 2023

AbstractThe objective of this research was to evaluate the efficacy of diclofenac sodium solutions, with or without cetrimide (CTR) added, against polymicrobial root canal biofilms grown in dentin specimens. The study groups were: (1) 5% diclofenac sodium (DCS); (2) 2.5% DCS; (3) 2.5% DCS + 0. 2% CTR; (4) 2.5% DCS + 0.4% CTR and (5) 0.9% saline solution (SS) as the control. After 5 min of solution contact with the biofilms, the antimicrobial activity was evaluated by means of the adenosine triphosphate (ATP) assay as well as confocal laser scanning microscopy (CLSM). Microbial quantification was indicated as the percentage reduction of relative light units (RLUs) for the ATP assay, the Log10 total biovolume and the viability percentage (green cells) for CLSM. Solutions of 2.5% DCS + 0.4% CTR and 5% DCS showed the highest antimicrobial efficacy. Cetrimide increased the antibiofilm activity of diclofenac sodium against endodontic biofilms.
Artificial intelligence governance: Ethical considerations and implications for social responsibility
Authors: Camilleri Mark Anthony 
Published: July 2023

AbstractA number of articles are increasingly raising awareness on the different uses of artificial intelligence (AI) technologies for customers and businesses. Many authors discuss about their benefits and possible challenges. However, for the time being, there is still limited research focused on AI principles and regulatory guidelines for the developers of expert systems like machine learning (ML) and/or deep learning (DL) technologies. This research addresses this knowledge gap in the academic literature. The objectives of this contribution are threefold: (i) It describes AI governance frameworks that were put forward by technology conglomerates, policy makers and by intergovernmental organizations, (ii) It sheds light on the extant literature on ‘AI governance’ as well as on the intersection of ‘AI’ and ‘corporate social responsibility’ (CSR), (iii) It identifies key dimensions of AI governance, and elaborates about the promotion of accountability and transparency; explainability, interpretability and reproducibility; fairness and inclusiveness; privacy and safety of end users, as well as on the prevention of risks and of cyber security issues from AI systems. This research implies that all those who are involved in the research, development and maintenance of AI systems, have social and ethical responsibilities to bear toward their consumers as well as to other stakeholders in society.