bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-ancestry Whole-exome Sequencing Study of Alcohol Use Disorder in Two Cohorts
Authors: Wang Lu , Kranzler Henry R. , Gelernter Joel , Zhou Hang 
Published: April 2024

AbstractAlcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, there are few whole-exome sequencing (WES) studies of AUD. We analyzed WES of 4,530 samples from the Yale-Penn cohort and 469,835 samples from the UK Biobank (UKB). After quality control, 1,420 AUD cases and 619 controls of European ancestry (EUR) and 1,142 cases and 608 controls of African ancestry (AFR) from Yale-Penn were retained for subsequent analyses. WES data from 415,617 EUR samples (12,861 cases), 6,142 AFR samples (130 cases) and 4,607 South Asian (SAS) samples (130 cases) from UKB were also analyzed. Single-variant association analysis identified the well-known functional variant rs1229984 inADH1B(P=4.88×10-31) and several other common variants inADH1C. Gene-based tests identifiedADH1B(P=1.00×10-31),ADH1C(P=5.23×10-7),CNST(P=1.19×10-6), andIFIT5(3.74×10-6). This study extends our understanding of the genetic basis of AUD.
Otolith shape variability of labrid fish from Rapa Nui (Easter Island), southeastern Pacific
Authors: Castro-García Andrés , Delrieu-Trottin Erwan , Saenz-Agudelo Pablo , Rapu-Edmunds Cristian , Plaza Guido , Márquez Federico , Landaeta Mauricio F. 
Published: April 2024

AbstractFish otolith shape provides valuable insights into the taxonomic, phylogenetic, and ecological traits of fish species. This study aimed to assess and compare the phenotypic variation in otolith shape among four labrid species (Anampses femininus, Coris debueni, Pseudolabrus fuentesiandThalassoma lutescens) inhabiting Rapa Nui (Easter Island) in the southeastern Pacific Ocean, utilizing geometric morphometrics and aging methods. Age estimation based on otolith structure indicated that collected specimens were adults, ranging between 1 and 3 years old. Allometric analysis revealed low but significant variation (5.40%), primarily driven by changes in otolith width, resulting in distinct morphologies. Principal Component Analysis (PCA) of sagittal otoliths elucidated significant morphospace variation among species, with the first two PCs explaining 60.3% of the total variance. PC1 distinguished between elongated sagittal shapes (e.g.,P. fuentesi) and robust sagittae (e.g.,T. lutescens), while PC2 correlated with otolith roundness, delineating variations within species. Canonical variate analysis further highlighted differences in otolith shape, with significant variations detected among all species. The Discriminant function analysis showed high levels of discrimination accuracy for most of species’ pairs. Except forC. debueni-P. fuentesi(89%) andC. debueni-T. lutescens(96%), all other species pairs achieved 100% discrimination, highlighting the reliability of otolith shape as a distinguishing characteristic for the studied species. Overall, our findings emphasize the value of otolith shape analysis for characterizing and distinguishing Rapa Nui labrid species. This offers potential applications such as identifying prey within the digestive systems of large fish or bird predators in the vicinity of this isolated island in the South Pacific Ocean or archaeofauna studies.
The persistence of memory: prior memory responses modulate behavior and brain state engagement
Authors: Wheelock Justin R. , Long Nicole M. 
Published: April 2024

SummaryMemory brain states may influence how we experience an event. Memory encoding and retrieval constitute neurally dissociable brain states that individuals can selectively engage based on top-down goals. To the extent that memory states linger in time – as suggested by prior behavioral work – memory states may influence not only the current experience, but also subsequent stimuli and judgments. Thus lingering memory states may have broad influences on cognition, yet this account has not been directly tested utilizing neural measures of memory states. Here we address this gap by testing the hypothesis that memory brain states are modulated by memory judgments, and that these brain states persist for several hundred milliseconds. We recorded scalp electroencephalography (EEG) while participants completed a recognition memory task. We used an independently validated multivariate mnemonic state classifier to assess memory state engagement. We replicate prior behavioral findings; however, our neural findings run counter to the predictions made on the basis of the behavioral data. Surprisingly, we find that prior responses modulate current memory state engagement on the basis of response congruency. That is, we find strong engagement of the retrieval state on incongruent trials – when a target is preceded by a correct rejection of a lure and when a lure is preceded by successful recognition of a target. These findings indicate that cortical brain states are influenced by prior judgments and suggest that a non-mnemonic, internal attention state may be recruited to in the face of changing demands in a dynamic environment.
Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions
Authors: Mowla Alireza , Hepburn Matt S. , Li Jiayue , Vahala Danielle , Amos Sebastian E. , Hirvonen Liisa M. , Sanderson Rowan W. , Wijesinghe Philip , Maher Samuel , Choi Yu Suk , Kennedy Brendan F. 
Published: April 2024

ABSTRACTCancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TME). While the shortcomings of two-dimensional (2D) models in replicatingin situcell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiologyin situ.
Genetic-based inference of densities, effective and census sizes of expanding riverine meta-populations of an invasive large-bodied freshwater fish (Silurus glanis L.)
Authors: Paz-Vinas Ivan , Loot Géraldine , Boulêtreau Stéphanie , Chiarello Marlène , Veyssière Charlotte , Ferriol Jessica , Santoul Frédéric 
Published: April 2024

AbstractEffective (Ne) and census (Nc) population sizes are key eco-evolutionary parameters. Jointly estimating them have an important practical value for efficient conservation and wildlife monitoring and management. Assessing Neand Ncremains however challenging for elusive, rare species or species inhabiting in complex habitats like large rivers. Genetic-based Neestimations could help resolve complex situations, as only a handful of genotyped individuals are needed to estimate Ne, and then NCcan be subsequently using an Ne/NCratio. However, most Neestimation methods are based on restrictive assumptions (e.g. Wright-Fisher model) making them inappropriate for inferring Neand Ncfor populations and species exhibiting complex dynamics. Here, we aimed at estimating Ne, NCand densities for meta-populations of a large invasive freshwater fish (the European catfishSilurus glanis) that has been introduced in the Garonne-Dordogne river basin (Southwestern France), using a framework that combines multiple data sources and approaches. First, we characterized spatial patterns of genetic variation using microsatellite genotype data, revealing a significant isolation by distance pattern informing about the species’ dispersal capacities. We then detected four genetically-distinct clusters of individuals coexisting in the river basin that might be the result of multiple introductions from different genetic sources. Further, we characterized the demographic expansion of the species at the river basin scale by analyzing data from a multidecadal demographic monitoring survey, and estimated a specific Ne/Nc ratio for this species. We finally combined all the gathered information to design four competing demo-genetic models accounting for all the complexity ofS. glanismeta-populations inhabiting the river basin. We simulated data under these models and then inferred Ne, Nc and densities through approximate Bayesian computation and random forest procedures. We show how multiple genetic and non-genetic approaches can be combined to estimate Neand Ncin hard-to-monitor meta-populations exhibiting complex demo-evolutionary dynamics.
Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2
Authors: Como Christina N. , O’Rourke Rebecca , Winkler Caitlin , Mitchell Danae , Tran Luuli , Lorberbaum David , Sussel Lori , Franco Santos , Siegenthaler Julie 
Published: April 2024

SummaryThe meninges act as a regulator of brain development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meningeal-derived retinoic acid (RA) promotes neocortical neural progenitor cell cycle exit; however, the underlying molecular mechanism is unknown. Here, we used spatial transcriptomics and profiling of retinoic-acid receptor-α (RARα) DNA binding inFoxc1-mutant embryos that lack meninges-derived ligands to identify the neurogenic transcriptional mechanisms of RA signaling in telencephalic neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing progenitor self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in theSox2otpromoter, a long non-coding RNA that regulatesSox2expression, and RA promotesSox2otexpression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of how meningeal RA coordinates neocortical development and insight into how defects in meningeal development may cause neurodevelopmental disorders.
Does Ethnicity Alters the Risk of Stroke in Patients with Modifiable Cardiometabolic Risk Factors?
Authors: Delord Marc , Ashworth Mark , Douiri Abdel 
Published: April 2024

AbstractBackgroundEthnic inequality in stroke risk was partially explained by history of hypertension, diabetes, and socioeconomic status. We aimed to estimate the impact of ethnicity on stroke risk in patients with hypertension, diabetes or hypercholesterolaemia.MethodsMultistate models were constructed using electronic health records including date at onset of stroke, stroke risk factors, and the Index of Multiple Deprivation in adult patients of Asian, Black, or White ethnicity, registered in 41 general practices in south London between 2005 and 2021. Transitions to hypertension, diabetes, or hypercholesterolaemia (transition 1) and from these risk factors to stroke (transitions 2) were considered.ResultsOf the 849,968 registered patients, 651,888 (76·7%) were of Asian (8·6%), Black (18·2%), or White (73·2%) ethnicity and 54·1% were female. Patients of Black ethnicity had higher incidence of stroke (2·1%) and cardiometabolic risk factors, whereas patients of Asian and White ethnicity had intermediate and lower levels of stroke (1·2% and 1·0% respectively) and cardiometabolic risk factors. Asian and Black ethnicities were associated with higher risks in transition 1 compared to White ethnicity. Ethnicity did not alter transition 2, except for hypercholesterolaemia, Black ethnicity being associated with higher risk of stroke compared to Asian and White ethnicity.ConclusionOur results confirm that Black ethnicity does not confer excess stroke risk in patients with hypertension or diabetes. This observation was also made for Asian ethnicity. Black ethnicity was associated with increased stroke risk only in patients with Hypercholesterolaemia.FundingGuys and St Thomas grant (EIC180702).
A collicular map for touch-guided tongue control
Authors: Ito Brendan S. , Gao Yongjie , Kardon Brian , Goldberg Jesse H. 
Published: April 2024

AbstractAccurate goal-directed behavior requires the sense of touch to be integrated with information about body position and ongoing motion1,2,3. Behaviors like chewing, swallowing and speech critically depend on precise tactile events on a rapidly moving tongue4,5, but neural circuits for dynamic touch-guided tongue control are unknown. Using high speed videography, we examined 3D lingual kinematics as mice drank from a water spout that unexpectedly changed position during licking, requiring re-aiming in response to subtle contact events on the left, center or right surface of the tongue. Mice integrated information about both precise touch events and tongue position to re-aim ensuing licks. Surprisingly, touch-guided re-aiming was unaffected by photoinactivation of tongue sensory, premotor and motor cortices, but was impaired by photoinactivation of the lateral superior colliculus (latSC). Electrophysiological recordings identified latSC neurons with mechanosensory receptive fields for precise touch events that were anchored in tongue-centered, head-centered or conjunctive reference frames. Notably, latSC neurons also encoded tongue position before contact, information important for tongue-to-head based coordinate transformations underlying accurate touch-guided aiming. Viral tracing revealed tongue sensory inputs to the latSC from the lingual trigeminal nucleus, and optical microstimulation in the latSC revealed a topographic map for aiming licks. These findings demonstrate for the first time that touch-guided tongue control relies on a collicular mechanosensorimotor map, analogous to collicular visuomotor maps associated with visually-guided orienting across many species.
RNA processing by the CRISPR-associated NYN ribonuclease
Authors: Chi Haotian , White Malcolm F 
Published: April 2024

AbstractCRISPR-Cas systems confer adaptive immunity in prokaryotes, facilitating the recognition and destruction of invasive nucleic acids. Type III CRISPR systems comprise large, multisubunit ribonucleoprotein complexes with a catalytic Cas10 subunit. When activated by the detection of foreign RNA, Cas10 generates nucleotide signalling molecules that elicit an immune response by activating ancillary effector proteins. Among these systems, theBacteroides fragilistype III CRISPR system was recently shown to produce a novel signal molecule, SAM-AMP, by conjugating ATP and SAM. SAM-AMP regulates a membrane effector of the CorA family to provide immunity. Here, we focus on NYN, a ribonuclease encoded within this system, probing its potential involvement in crRNA maturation. Structural modelling andin vitroribonuclease assays reveal that NYN displays robust sequence-nonspecific, Mn2+-dependent ssRNA-cleavage activity. Our findings suggest a role for NYN in trimming crRNA intermediates into mature crRNAs, which is necessary for type III CRISPR antiviral defence. This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.
Chemical tools to define and manipulate interferon-inducible Ubl protease USP18
Authors: Davis Griffin J. , Omole Anthony O. , Jung Yejin , Rut Wioletta , Holewinski Ronald , Suazo Kiall F. , Kim Hong-Rae , Yang Mo , Andresson Thorkell , Drag Marcin , Yoo Euna 
Published: April 2024

AbstractUbiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating interferon-inducible ubiquitin-like (Ubl) modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) capable of selectively detecting USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) by incorporating unnatural amino acids into the C-terminal tail of ISG15. Combining with a ubiquitin-based DUB ABP, the selective USP18 ABP is employed in a chemoproteomic screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.
Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP
Authors: Ojha Ruchi , Krug Stefanie , Jones Prentiss , Koestler Benjamin J. 
Published: April 2024

AbstractThe intracellular human pathogenShigellainvades the colonic epithelium to cause disease. Prior to invasion, this bacterium navigates through different environments within the human body, including the stomach and the small intestine. To adapt to changing environments,Shigellauses the bacterial second messenger c-di-GMP signaling system, synthesized by diguanylate cyclases (DGCs) encoding GGDEF domains.Shigella flexneriencodes a total of 9 GGDEF or GGDEF-EAL domain enzymes in its genome, but 5 of these genes have acquired mutations that presumably inactivated the c-di-GMP synthesis activity of these enzymes. In this study, we examined individualS. flexneriDGCs for their role in c-di-GMP synthesis and pathogenesis. We individually expressed each of the 4 intact DGCs in anS. flexneristrain where these 4 DGCs had been deleted (Δ4DGC). We found that the 4S. flexneriintact DGCs synthesize c-di-GMP at different levelsin vitroand during infection of tissue-cultured cells. We also found thatdgcFanddgcIexpression significantly reduces invasion and plaque formation, anddgcFexpression increases acid sensitivity, and that these phenotypes did not correspond with measured c-di-GMP levels. However, deletion of these 4 DGCs did not eliminateS. flexneric-di-GMP, and we found thatdgcE, dgcQ,anddgcN, which all have nonsense mutations prior to the GGDEF domain, still produce c-di-GMP. TheseS. flexneridegenerate DGC genes are expressed as multiple proteins, consistent with multiple start codons within the gene. We propose that both intact and degenerate DGCs contribute toS. flexneric-di-GMP signaling.
Neural and behavioral similarity-driven tuning curves for manipulable objects
Authors: Valério D. , Peres A. , Bergström F. , Seidel P. , Almeida J. 
Published: April 2024

AbstractIn our daily activities, we encounter numerous objects that we successfully distinguish and recognize within a fraction of a second. This holds for coarse distinctions (e.g., cat vs. hammer) but also for more challenging within-category distinctions that require fine-grain analysis (e.g., cat vs. dog). The efficiency of this recognition depends on how the brain organizes object-related information. While several attempts have focused on unravelling large-scale organization principles, research on within-category organization of knowledge is rather limited. Here, we explored the fine-grain organization of object knowledge and investigated whether manipulable objects are organized and represented in terms of their similarity. To accomplish this, different groups of individuals participated in a behavioral and fMRI release from adaptation experiment. Adaptation was induced by presenting different exemplars of a particular object, and release from adaptation was elicited by the presentation of a deviant object. The relationship between adaptation and deviant objects was manipulated into four levels of similarity, measured by feature overlap between these objects. Our findings revealed that increasing object similarity provoked progressively slower reaction times and progressively weaker fMRI release from adaptation. Specifically, we identified similarity-driven tuning curves for the release from adaptation in the medial fusiform, collateral sulcus, parahippocampal gyri, lingual gyri, lateral occipital complex, and occipito-parietal cortex. These results suggest that the processing and representation of objects in the brain and our ability to perform fine discriminations between objects reflect real-world object similarity in a relatively parametric manner.
Mediating effects of relationship marketing orientation and service quality orientation on policyholder retention in non-life insurance services
Authors: Yu Tsu-Wei 
Published: April 2024

PurposeThis study explores the mediating effects of relationship marketing orientation (RMO) and service quality orientation (SQO) on market orientation, selling orientation, and policyholder retention in non-life insurance services. Additionally, it offers important recommendations for non-life insurers in Taiwan for policy development and improving policyholder retention.Design/methodology/approachData were collected from a sample of policyholders belonging to the top five non-life insurance companies in Taiwan. The data were then analyzed with structural equation modeling.FindingsRMO and SQO mediate the effects of the salesperson’s market orientation on policyholder retention. Thus, RMO and SQO are key factors influencing policyholder retention. Consequently, high levels of market orientation should be maintained to increase RMO and SQO, strengthening the retention rate of non-life insurance policyholders.Research limitations/implicationsThe main limitation of this study is its cross-sectional nature. In the future, researchers should collect data from other countries and service industries (e.g. banks, securities, and other financial institutions), expand to different insurance contexts (e.g. life insurance), and conduct longitudinal studies or experimental research.Practical implicationsThe results of this study can act as a guide for providers of non-life insurance services. Based on the research results, we recommend decision-makers pay increased attention to increasing policyholder retention rates by strengthening their firm’s RMO and SQO.Originality/valueFew studies have investigated the relationships among market orientation, selling orientation, RMO, SQO, and policyholder retention in non-life insurance services within Asian contexts in general and specifically in Taiwan. Thus, this study’s theoretical contributions, managerial implications (especially for decision-makers), and the proposed future research directions represent timely and valuable additions to the literature.