bluuebunny/crossref_metadata_2025_split huggingface dataset:
RluA is the major mRNA pseudouridine synthase inEscherichia coli
Authors: Schaening-Burgos Cassandra , Li Gene-Wei , Gilbert Wendy 
Published: December 2023

AbstractPseudouridine (Ψ) is an ubiquitous RNA modification, present in the tRNAs and rRNAs of species across all domains of life. Conserved pseudouridine synthases modify the mRNAs of diverse eukaryotes, but the modification has yet to be identified in bacterial mRNAs. Here, we report the discovery of pseudouridines in mRNA fromE. coli. By testing the mRNA modification capacity of all 11 known pseudouridine synthases, we identify RluA as the predominant mRNA-modifying enzyme. RluA, a known tRNA and 23S rRNA pseudouridine synthase, modifies at least 31 of the 44 high-confidence sites we identified inE. colimRNAs. Using RNA structure probing data to inform secondary structures, we show that the target sites of RluA occur in a common sequence and structural motif comprised of a ΨURAA sequence located in the loop of a short hairpin. This recognition element is shared with previously identified target sites of RluA in tRNAs and rRNA. Overall, our work identifies pseudouridine in key mRNAs and suggests the capacity of Ψ to regulate the transcripts that contain it.Author SummaryWhile RNAs are initially transcribed using only the nucleotides A, G, C and U, these can be enzymatically modified into many different post-transcriptional modifications. tRNAs and rRNAs across all domains of life are modified with pseudouridine, an isoform of uridine that is inserted by highly conserved enzymes. In many eukaryotes, it has been demonstrated that some of these enzymes can also insert pseudouridines in mRNA, where they are poised to impact gene expression through their effects on the transcript. Here we show that protein-coding transcripts inE. coliare also modified with pseudouridine, indicating that mRNA pseudouridylation is also a highly conserved activity. RluA is the main mRNA pseudouridine synthase, introducing the modification into the transcripts of dozens of protein coding genes with high specificity. Its target sites are defined by a combined sequence and secondary structure motif. Two additional enzymes, RluC and RluD, introduce a few additional sites. All three of these enzymes belong to the same sub-family of pseudouridine synthases, and homologs of these also modify mRNAs in humans. Thus, mRNA modification by these enzymes might be a conserved activity with the capacity to impact gene regulation.
When to attend? Temporal attention interacts with expectation
Authors: Duyar Aysun , Ren Shiyang , Carrasco Marisa 
Published: December 2023

ABSTRACTTemporal attention is voluntarily deployed at specific moments, whereas temporal expectation is deployed according to timing probabilities. When the target appears at an expected moment in a sequence, temporal attention improves performance at the attended moments, but the timing and the precision of the attentional window remain unknown. Here we independently and concurrently manipulated temporal attention–via behavioral relevance–and temporal expectation–via session-wise precision and trial-wise hazard rate–to investigate whether and how these mechanisms interact to improve perception. Our results reveal that temporal attention interacts with temporal expectation–the higher the precision, the stronger the attention benefit, but surprisingly this benefit decreased with delayed onset despite the increasing probability of stimulus appearance. When attention was suboptimally deployed to earlier than expected moments, it could not be reoriented to a later time point. These findings provide evidence that temporal attention and temporal expectation are different mechanisms, and highlight their interplay in optimizing visual performance.RelevanceOur ability to process visual information is limited both across space and time. Here we disentangle how two mechanisms–attention and expectation–help us overcome temporal limitations. We concurrently manipulated attention and expectation independently to investigate whether and how they interact. We found that temporal attention interacts with two distinct forms of expectation. Temporal expectation strengthens the benefits of temporal attention on performance for the attended time points, depending on how precise the expectations are. Surprisingly, the advantages of attention decrease when stimuli occur later than expected, suggesting a limitation of attention to reorient from earlier to later time points. This study provides further evidence that humans cannot sustain temporal attention even over short periods, reveals that although temporal attention and expectation interact to improve visual performance, expectation suboptimally guides attention, and highlights that attention and expectation are different temporal mechanisms.
Multi-assay approach shows species-associated personality patterns in two socially distinct gerbil species
Authors: Tchabovsky Andrey V. , Surkova Elena N. , Savinetskaya Ludmila E. 
Published: December 2023

AbstractWe aimed to investigate whether two closely related but socially distinct species of gerbils differ in personality patterns. Using a suit of multivariate repeated assays (docility test, dark-light emergence test, startle test, novel object test, elevated platform test, and stranger test), we assessed contextual and temporal consistency of docility, boldness, exploration, anxiety, and sociability in the solitary midday gerbil,Meriones meridianus, and social Mongolian gerbil,M. unguiculatus. We revealed contextually consistent and highly repeatable sex-independent but species-specific personality traits. Species differed in temporal repeatability of different behaviours, and contextual consistency was more pronounced in solitaryM. meridianusthan in socialM. unguiculatus. This finding contradicts the social niche specialization hypothesis, which suggests that personality traits should be more consistent in more social species. Instead, we hypothesize that social complexity should favour more flexible and less consistent behavioural traits. The habituation effect indicative of learning abilities was weak in both species yet stronger in socialM. unguiculatus, supporting the relationship between the sociality level and cognitive skills. In both species, only a few different behavioural traits covaried, and the sets of correlated behaviours were species-specific such that the two species did not share any pair of correlated traits. Between-species differences in personality traits, habituation, and behavioural syndromes may be linked to differences in sociality. The lack of prominent behavioural syndromes is consistent with the idea that context-specific individual behavioural traits might be favoured to allow more flexible and adequate responses to changing environments than syndromes of correlated functionally different behaviours.
A Bayesian Approach to Non-Metric Hyperbolic Multi-Dimensional Scaling
Authors: Jolis Milo , Praturu Anoop , Sharpee Tatyana 
Published: December 2023

AbstractThis paper explores the intersection of hyperbolic geometry, non-metric techniques, and Bayesian frameworks to extend the capabilities of Bayesian Hyperbolic Multi-Dimensional Scaling (HMDS). While hyperbolic geometry is gaining attention for its ability to represent hierarchical relationships, traditional metrics impose constraints on distances. Non-metric techniques offer flexibility in capturing complex structures, making them suitable for scenarios where metric distances are less meaningful. The paper introduces a novel extension of Bayesian HMDS, incorporating non-metric techniques, enabling the embedding of Euclidean data within a hyperbolic space. The approach simultaneously fits for curvature and coordinates, leveraging the scaling properties of hyperbolic space. The non-metric Bayesian Hyperbolic MDS is expected to unveil new insights into hierarchical structures within complex datasets, providing a versa-tile tool for analyzing high-dimensional data flexibly and accurately. The efficacy of the proposed method is demonstrated through synthetic data experiments, showcasing its ability to capture non-linear transformations and accurately predict underlying curvature, with an emphasis on its ro-bustness to hyperparameter choices.
Improving peripheral reading with non-invasive transcranial electrical stimulation of early visual areas
Authors: Silva Andrew E. , Mungalsingh Melanie A. , Raudzus Louise , Thompson Benjamin 
Published: December 2023

AbstractWe investigated the ability of two non-invasive transcranial electrical stimulation (tES) protocols targeting early visual areas to improve peripheral visual word recognition in separate within-subject, double-blind, sham-controlled experiments with normal observers. English sentences were presented 10 degrees below fixation using a rapid serial visual presentation (RSVP). Transcranial random noise stimulation (tRNS) applied bilaterally on either size of the occipital pole (Oz) elicited a significant performance benefit, but transcranial direct current stimulation (tDCS) applied to Oz did not. These results highlight important factors that may influence the effectiveness of non-invasive brain stimulation methods for enhancing peripheral processing of text, such as stimulation type. While more work is necessary to better understand the relationship between tES and peripheral reading, the present results contribute to the growing body of work implicating tES as a potential tool for enhancing peripheral visual processing.
Cardiomyocyte Globotriaosylceramide Accumulation in Adult Male Patients with Fabry Disease and IVS4 + 919G>A GLA Mutation is Progressive with Age and Correlates with Left Ventricular Hypertrophy and Reduced Left Ventricular Ejection Fraction
Authors: Chang Fu-Pang , Hsu Ting-Rong , Hung Sheng-Che , Sung Shih-Hsien , Yu Wen-Chung , Niu Dau-Ming , Najafian Behzad 
Published: December 2023

AbstractBackgroundWhile cardiovascular complications are the most common cause of mortality in Fabry disease, the relationship between globotriaosylceramide (GL-3) accumulation, the hallmark of Fabry cardiomyopathy, and cardiac hypertrophy has not been fully elucidated.MethodsWe developed unbiased stereology protocols to quantify the ultrastrcture of Fabry cardiomyopathy. Endomyocardial biopsies from 10 adult male enzyme replacement therapy naïve Fabry patients with IVS4 + 919G>A GLA mutation were studied. The findings were correlated with cardiac MRI and clinical data.ResultsUltrastructural parameters showed significant relationships with key imaging and clinical and functional variables. Average cardiomyocyte volume and GL-3 volume per cardiomyocyte were progressively increased with age. Eighty-four percent of left ventricular mass index (LVMI) variability was explained by cardiomyocyte nuclear volume, age and plasma globotriaosylsphingosine with cardiomyocyte nuclear volume being the only independent predictor of LVMI. Septal thickness was directly and left ventricular ejection fraction (LVEF) was inversely correlated with cardiomyocyte GL-3 accumulation. Sixty-five percent of left ventricular ejection fraction (LVEF) variability was explained by cardiomyocyte GL3 volume, serum α-galactosidase-A activity and age with cardiomyocyte GL3 volume being the only independent predictor of LVEF. Residual α-galactosidase-A activity was directly correlated with myocardial microvasculature density.ConclusionsThe unbiased stereological methods introduced in this study unraveled novel relationships between cardiomyocyte structure and important imaging and clinical parameters. These novel tools can help better understand Fabry cardiomyopathy pathophysiology.Clinical PerspectiveWhat is new?We developed a novel unbiased quantitative approach to study cardiac biopsies by electron microscopy.Ultrastructural parameters showed significant relationships with key clinical, imaging, cardiac functional variables in cardiac biopsies from patients with Fabry disease.What are the clinical implications?These quantitative approaches are powerful tools to better understand pathophysiology of Fabry disease and potentially in other cardiomyopathies.
Polygenic prediction of human longevity on the supposition of pervasive pleiotropy
Authors: Jabalameli M.Reza , Lin Jhih-Rong , Zhang Quanwei , Wang Zhen , Mitra Joydeep , Nguyen Nha , Gao Tina , Khusidman Mark , Atzmon Gil , Milman Sofiya , Vijg Jan , Barzilai Nir , Zhang Zhengdong D. 
Published: December 2023

ABSTRACTThe highly polygenic nature of human longevity renders cross-trait pleiotropy an indispensable feature of its genetic architecture. Leveraging the genetic correlation between the aging-related traits (ARTs), we sought to model the additive variance in lifespan as a function of cumulative liability from pleiotropic segregating variants. We tracked allele frequency changes as a function of viability across different age bins and prioritized 34 variants with an immediate implication on lipid metabolism, body mass index (BMI), and cognitive performance, among other traits, revealed by PheWAS analysis in the UK Biobank. Given the highly complex and non-linear interactions between the genetic determinants of longevity, we reasoned that a composite polygenic score would approximate a substantial portion of the variance in lifespan and developed the integrated longevity genetic scores (iLGSs) for distinguishing exceptional survival. We showed that coefficients derived from our ensemble model could potentially reveal an interesting pattern of genomic pleiotropy specific to lifespan. We assessed the predictive performance of our model for distinguishing the enrichment of exceptional longevity among long-lived individuals in two replication cohorts and showed that the median lifespan in the highest decile of our composite prognostic index is up to 4.8 years longer. Finally, using the proteomic correlates ofiLGS, we identified protein markers associated with exceptional longevity irrespective of chronological age and prioritized drugs with repurposing potentials for gerotherapeutics. Together, our approach demonstrates a promising framework for polygenic modeling of additive liability conferred by ARTs in defining exceptional longevity and assisting the identification of individuals at higher risk of mortality for targeted lifestyle modifications earlier in life. Furthermore, the proteomic signature associated withiLGShighlights the functional pathway upstream of the PI3K-Akt that can be effectively targeted to slow down aging and extend lifespan.
Cold Atmospheric Helium Plasma in the Post-Covid Era: A Promising Tool for the Disinfection of Silicone Endotracheal Prostheses
Authors: da Silva Diego Morais , do Nascimento Fellype , Milhan Noala Vicensoto , de Oliveira Maria Alcionéia Carvalho , Guerreiro Cardoso Paulo Francisco , Legendre Daniel , Aoki Fabio Gava , Kostov Konstantin Georgiev , Koga-Ito Cristiane Yumi 
Published: December 2023

ABSTRACTThe COVID-19 pandemic resulted in a high prevalence of laryngotracheal stenosis. The endoluminal tracheal prostheses used to treat this condition are made of medical-grade silicone (MGS). Despite their excellent properties, the main limitation of these prostheses is the formation of a polymicrobial biofilm on their surfaces that interacts with the underlying mucosa, causing local inflammation and interfering with the local healing process, ultimately leading to further complications in the clinical scenario. Cold atmospheric plasma (CAP) shows antibiofilm properties on several microbial species. The present study evaluated the inhibitory effect of CAP on multispecies biofilms grown on MGS surfaces. In addition to the MGS characterization before and after CAP exposure, the cytotoxicity of CAP on immortalized human bronchial epithelium cell line (BEAS-2B) was evaluated. The aging time test reported that CAP could temporarily change the MGS surface wetting characteristics from hydrophilic (80.5°) to highly hydrophilic (< 5°). ATR-FTIR shows no significant alterations in the surficial chemical composition of MGS before and after CAP exposure for 5 min. A significant log reduction of viable cells in mono-species biofilms (log CFU/mL) ofC. albicans, S. aureus, andP. aeruginosa(0.636, 0.738, and 1.445, respectively) was detected after CAP exposure. Multi-species biofilms exposed to CAP showed significant viability reduction forC. albicansandS. aureus(1.385 and 0.831, respectively). The protocol was not cytotoxic to BEAS-2B. It could be concluded that CAP can be a simple and effective method to delay the multi-species biofilm formation inside the endotracheal prosthesis.
GOAT: efficient and robust identification of geneset enrichment
Authors: Koopmans Frank 
Published: December 2023

ABSTRACTGeneset enrichment analysis is foundational to the interpretation of high throughput biology. We here present GOAT (https://ftwkoopmans.github.io/goat), a parameter-free permutation-based algorithm for geneset enrichment analysis of preranked genelists. Estimated geneset p-values are well calibrated under the null hypothesis and invariant to geneset size. GOAT consistently identifies more Gene Ontology terms in real-world datasets than current methods and is available as an R package and online tool.
Cognitive Phenotype Shifts in Risk-Taking: Interplay of Non-Suicidal Self-Injury Behaviors and Intensified Depression
Authors: Lu Yi-Long , Ge Yuqi , Li Mingzhu , Liang Shutian , Zhang Xiaoxi , Sui Yupeng , Yang Lei , Li Xueni , Zhang Yuyanan , Yue Weihua , Zhang Hang , Yan Hao 
Published: December 2023

AbstractBackgroundNon-suicidal self-injury (NSSI) behavior is significantly prevalent in both adolescents and psychiatric populations, particularly in individuals with major depressive disorder (MDD). NSSI can be considered a result of risky decision-making in response to negative emotions, where individuals choose self-harm over other less harmful alternatives, suggesting a potential decision-making deficit in those engaging in NSSI. This study delves into the complex relationship between NSSI and depression severity in decision-making and its cognitive underpinnings.MethodsWe assessed decision behaviors in 57 MDD patients with NSSI, 42 MDD patients without NSSI and 142 healthy controls using the Balloon Analogue Risk Task, which involves risk-taking, learning, and exploration in uncertain scenarios. Using computational modeling, we dissected the nuanced cognitive dimensions influencing decision behaviors. A novel statistical method was developed to elucidate the interaction effects between NSSI and depression severity.ResultsContrary to common perceptions, we found that individuals with NSSI behaviors were typically more risk-averse. Meanwhile, there was a complex interaction between NSSI and depression severity in shaping risk-taking behaviors. As depressive symptoms intensified, these individuals with NSSI began to perceive less risk and behave more randomly.ConclusionsThis research provides new insights into the cognitive aspects of NSSI and depression, highlighting the importance of considering the influence of comorbid mental disorders when investigating the cognitive underpinnings of such behaviors, especially in the context of prevalent cross-diagnostic phenomena like NSSI behaviors.
Empowering human-like walking with a bio-inspired gait controller for an under-actuated torque-driven human model
Authors: Amini Samane , Kardan Iman , Seth Ajay , Akbarzadeh Alireza 
Published: December 2023

AbstractHuman gait simulation plays a crucial role in providing insights into various aspects of locomotion, such as diagnosing injuries and impairments, assessing abnormal gait patterns, and developing assistive and rehabilitation technologies. To achieve more realistic results in gait simulation, it is necessary to utilize a comprehensive model that closely replicates the kinematics and kinetics of the human gait pattern. OpenSim software provides anthropomorphic and anatomically accurate human skeletal structures that enable users to create personalized models for individuals to accurately replicate real human behavior. However, torque-driven models face challenges in balancing unactuated degrees of freedom during forward dynamic simulations. Adopting a bio-inspired strategy that ensures an individual’s balance with a minimized energy expenditure, this paper proposes a gait controller for a torque-deriven OpenSim model to achieve a stable walking. The proposed controller takes a model-based approach to calculate a “Balance Equivalent Control Torque” and uses the concept of the hip-ankle strategy to distribute this balance torque to the lower-limb joints. To optimize the controller gains and the “Balance Distribution Coefficients”, an interface is stablished between MATLAB and OpenSim that is capable of conducting controllable forward dynamic simulations. The simulation results demonstrate that the torque-driven model can walk naturally with joint torques suitably matching experimental data. The robustness of the bio-inspired gait controller is also assessed by applying a range of external forces on the upper body to disturb the model. The robustness analysis demonstrates the quick and effective balance recovery mechanism of the proposed bio-inspired controller.
An Automatic Glaucoma Grading Method Based on Attention Mechanism and EfficientNet-B3 Network
Authors: Zhang Xu , Lai Fuji , Chen Weisi , Yu Chengyuan 
Published: December 2023

AbstractDeep learning has received considerable attention in the computer vision field and has been widely studied, especially in recognizing and diagnosing ophthalmic diseases. Currently, glaucoma recognition algorithms are mostly based on unimodal OCT, the visual field for glaucoma auxiliary diagnosis. Such algorithms have poor robustness and limited help for glaucoma auxiliary diagnosis; therefore, this experiment is proposed to use a 2D fundus image and 3D-OCT scanner two modal data as the experimental dataset and use the EfficientNet-B3 network and ResNet34 network models for feature extraction and fusion to improve automatic glaucoma grading accuracy. Since fundus images usually contain a large number of meaningless black background regions, this may lead to feature redundancy. Therefore, this experiment employs an attention mechanism that focuses the attention of the convolutional neural network on eye subject features to improve the performance of the glaucoma autoclassification model.
Latent Dirichlet Allocation Mixture Models for Nucleotide Sequence Analysis
Authors: Wang Bixuan , Mount Stephen M. 
Published: December 2023

AbstractStrings of nucleotides that carry biological information are typically described using sequence motifs that can be represented by weight matrices or consensus sequences. However, many biological signals in DNA or RNA are recognized by multiple factors in temporal sequence, consist of a mixture of sometimes dissimilar alternative motifs, or may be described better by base composition. Here we apply the Latent Dirichlet Allocation (LDA) mixture model to nucleotide sequences, using k-mers as features, in three related approaches. First, positions in aligned sequences are used as samples. Alternatively, whole sequences are used as samples, either with positional k-mers or with bulk k-mers occurring throughout the sequence. LDA readily identifies motifs, including such elusive cases as the intron branch site. LDA can also identify subtypes of sequence, such as splice site subtypes enriched in long vs. short introns, and can reliably distinguish such properties as reading frame or species of origin. Our results show that LDA is a useful model for describing heterogeneous signals, for assigning individual sequences to subtypes, and for identifying and characterizing sequences that do not fit recognized subtypes. Because LDA topic models are interpretable, they also aid the discovery of new motifs, even those present in a small fraction of samples, allowing a user to hypothesize potential regulatory factors. In summary, LDA can identify and characterize signals in nucleotide sequences and is useful for identifying candidate regulatory factors involved in complex biological processes.