bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Exploratory EEG Comparison of Good and Bad Readers
Authors: Álvarez-Alonso María José , de la Peña Cristina , Scott Ricardo 
Published: December 2024

ABSTRACTReading is a crucial skill for critical thinking and cognitive development, yet many individuals experience difficulties that impact their daily lives. This study examines the neurophysiological differences between proficient and struggling readers using electroencephalography (EEG). The analysis focuses on the alpha (8-12 Hz) and beta (13-30 Hz) frequency bands, which are prominently involved in cognitive and language-related processes, although other frequency bands also contribute significantly to language comprehension and cognitive control. Eighteen participants (9 good readers and 9 poor readers) were selected based on standardized reading assessments. Resting-state EEG recordings were collected with a 64-channel system while participants were at rest with their eyes closed. After preprocessing to remove artifacts, the power spectra were analyzed, emphasizing relative power and alpha peak activity. Functional connectivity was measured using the corrected imaginary part of the phase-locking value (ciPLV), ensuring accuracy by minimizing volume conduction effects. Results revealed that good readers displayed increased beta power in frontal regions and enhanced synchronization within fronto-central-parietal networks compared to poor readers. Alpha band activity showed complex associations with factors such as age, reading skills, and verbal fluency, indicating nuanced relationships between neural development and literacy. The heightened beta activity in good readers is consistent with its role in cognitive control and language processing, while their stronger network connectivity suggests more efficient neural communication. These findings provide valuable insights into the neural basis of reading proficiency and emphasize the importance of distributed brain networks in skilled reading. Future research should replicate these results with larger samples and longitudinal designs to better understand the neural mechanisms underlying literacy development.
OST component RPN1 is a novel regulator of IRE1 RNase activity that interacts with multiple distinct IRE1 and PERK complexes
Authors: Larburu Natacha , Storer Freya , Ben-Khoud Yassin , Chen Chao-Sheng , Adams Christopher J , Southall Tony D , Ali Maruf MU 
Published: December 2024

AbstractThe unfolded protein response (UPR) is an essential cell signalling system that regulates ER protein homeostasis. IRE1 and PERK are receptor proteins that propagate the UPR signal from the ER to the cytosol. Both receptors are suggested to interact with various proteins from different biological pathways, although the scale and scope of such interactions are unclear. Previous reconstitution experiments have utilized purified isolated domains of IRE1 and PERK to understand mechanism. Here, we affinity purify full length IRE1 and PERK from mammalian cells and characterise the complexes they form by biochemical techniques and assess RNase function in vivo. We identify RPN1 as a novel interacting protein present in complexes with IRE1 and PERK. In the Drosophila eye, RNAi knockdown of RPN1 results in loss of IRE1 RNase activity. This work provides a basis for understanding of protein interaction networks for IRE1 and PERK and identifies OST subunit RPN1 as a novel regulator of IRE1 RNase activity.
METTL7A improves bovine IVF embryo competence by attenuating oxidative stress
Authors: Zhu Linkai , Ming Hao , Scatolin Giovanna N. , Xiao Andrew , Jiang Zongliang 
Published: December 2024

AbstractIn vitro fertilization (IVF) is a widely used assisted reproductive technology to achieve a successful pregnancy. However, the acquisition of oxidative stress in embryo in vitro culture impairs its competence. Here, we demonstrated that a nuclear coding gene, methyltransferase- like protein 7A (METTL7A), improves the developmental potential of bovine embryos. We found that exogenous METTL7A modulates expression of genes involved in embryonic cell mitochondrial pathways and promotes trophectoderm development. Surprisingly, we discovered that METTL7A alleviates mitochondrial stress and DNA damage and promotes cell cycle progression during embryo cleavage. In summary, we have identified a novel mitochondria stress eliminating mechanism regulated by METTL7A that occurs during the acquisition of oxidative stress in embryo in vitro culture. This discovery lays the groundwork for the development of METTL7A as a promising therapeutic target for IVF embryo competence.Summary statement (Graphic abstract)We describe a molecule acts in the pre-implantation period to attenuate oxidative stress that enhances embryo development to the blastocyst stage and subsequent pregnancy in cattle.
Mathematical bounds onr2and the effect size in case-control genome-wide association studies
Authors: Paye Sanjana M. , Edge Michael D. 
Published: December 2024

AbstractCase-control genome-wide association studies (GWAS) are often used to find associations between genetic variants and diseases. When case-control GWAS are conducted, researchers must make decisions regarding how many cases and how many controls to include in the study. Depending on differing availability and cost of controls and cases, varying case fractions are used in case-control GWAS. Connections between variants and diseases are made using association statistics, includingχ2. Previous work in population genetics has shown that LD statistics, includingr2, are bounded by the allele frequencies in the population being studied. Since varying the case fraction changes sample allele frequencies, we extend use the known bounds onr2to explore how variation in the fraction of cases included in a study can impact statistical power to detect associations. We analyze a simple mathematical model and use simulations to study a quantity proportional to theχ2noncentrality parameter, which is closely related tor2, under various conditions. Varying the case fraction changes theχ2noncentrality parameter, and by extension the statistical power, with effects depending on the dominance, penetrance, and frequency of the risk allele. Our framework explains previously observed results, such as asymmetries in power to detect risk vs. protective alleles, and the fact that a balanced sample of cases and controls does not always give the best power to detect associations, particularly for highly penetrant minor risk alleles that are either dominant or recessive. We show by simulation that our results can be used as a rough guide to statistical power for association tests other thanχ2tests of independence.
The transcriptomic signature of age and sex is not conserved in human primary myocytes
Authors: Lamon Séverine , Soria Megan , Williams Ross , Critchlow Annabel , Garnham Andrew , Varshney Akriti , Beillharz Traude , Hiam Danielle , Ziemann Mark 
Published: December 2024

AbstractHuman primary muscle cell (HPMC) lines derived from skeletal muscle biopsies are potentially powerful tools to interrogate the molecular pathways underlying fundamental muscle mechanisms. HPMCs retain their genome in culture, but many endogenous circulating factors are not present in thein vitroenvironment or at concentrations that do not mirror physiological levels. To address the assumption that HPMCs are valid models of age and sex-specificity in human muscle research, we examined to what extent HPMC lines maintain their source phenotypes in culture. A comparison of the transcriptomic signature of 30 human muscle biopsies (N = 10 young males, N = 10 young females, N = 10 old males) and their corresponding HPMCs indicated a near-complete lack of retention of the genes and pathways that were differentially regulatedin vivowhen compared to theirin vitroequivalent, except for some genes encoded on the Y-chromosome. The diversity of the muscle cell population and the lack of sex- and age-dependent factors in the cellular milieu likely contribute to these observations, which call for caution when using HPMCs as an experimental model of human muscle sex or age. Nuclear single cell sequencing or HMPCs grown in 3D culture as organoids under strain might therefore provide a closer alternative to human muscle tissue.
Naturalistic language comprehension engages a cascade of widespread brain networks in the one second following comprehension
Authors: Hong Min Kyung , Janson Andrew , Koirala Prasanna , Fotidzis Tess , Polyn Sean , Aboud Katherine 
Published: December 2024

AbstractLanguage comprehension (LC) is a cornerstone of human cognition, enabling the extraction of meaning from written and spoken communication with remarkable efficiency. Decades of neuroimaging research have identified the brain networks associated with LC, but limitations in spatial and temporal resolution have hindered a comprehensive characterization of the whole-brain (millimeter scale), real-time (millisecond precision) dynamics underlying this process. To overcome these constraints, we applied a fusion of multimodal brain imaging techniques (fMRI and EEG) in healthy adults (n = 30) to map the spatiotemporal progression of neural network engagement during LC in the one second following comprehension. Our findings reveal a cascade of brain network activations, beginning with the occipitotemporal perceptual word processing network (250 ms), followed by the temporoparietal semantic retrieval network (400 ms), the posterior default mode inferential network (500 ms), the frontotemporal semantic integration network (600 ms), and finally, a distributed goal-directed comprehension network (700 ms). Crucially, inferential processing emerged as a “hinge point,” linking early word processing to later higher-order networks. Efficient LC was associated with greater mediation by this inferential network and reduced reliance on top-down semantic integration. These findings provide evidence that naturalistic LC relies on rapid, dynamic interactions across widespread brain networks, with individual differences in LC reflecting specific subnetwork interactions. This work offers a framework for investigating the temporal evolution of distributed brain network dynamics in complex cognition across domains and clinical populations.
Widespread annual rhythms in pediatric emergencies
Authors: Tachinardi Patricia , Witt Rochelle M , Wu Gang , Paulose Jiffin K , Koritala Bala S C , Wong Hector R , Mendonca Eneida A , Smith David F , Hogenesch John B , Ruben Marc D 
Published: December 2024

AbstractAssessments of emergency department (ED) utilization for specific medical conditions reveal distinct annual rhythms, providing valuable insights into risk factors and optimal clinical staffing. However, focusing on a single condition in isolation can lack essential context. Such rhythms may (i) depend on co-occurrence with other conditions, (ii) be obscured by systemic factors that influence all conditions similarly, or (iii) offer limited clinical utility without understanding their rhythmic effect sizes relative to other emergencies. Using a unified framework for analysis, we studied the annual variation in incidences of all chief complaints (CCs) from 1.5 million admissions to our pediatric ED and urgent care centers from 2010 to 2021, enabling comparison of seasonality, effect sizes, and interactions across all types of emergencies. Most CCs (∼80%) had annual rhythms, with a range of phases. Specific patterns, such as spring and fall peaks in neurologic-, injury-, and psychiatric-related CCs, have immediate significance. For example, psychiatric emergencies, which the American Academy of Pediatrics has designated a national crisis, were among the largest rhythmic effect sizes of all CCs. Further evaluation integrating ICD-10 diagnoses identified patient subtypes for psychiatric and other CCs, suggesting distinct annual influences. Using counterpart data from across Brazil, we identified marked global differences in annual patterns of ED utilization, including psychiatric emergencies. Lastly, we identified CCs with largeweekdayeffects, impacting care and staffing needs, especially when combined with annual rhythms.
Subregional analysis of the amygdala, thalamus, and hypothalamus at the pre-decline stage in Parkinson’s disease groups with later cognitive impairment
Authors: Seo Kazuhide , Oyama Genko , Yamamoto Toshimasa 
Published: December 2024

AbstractWhile cognitive decline in Parkinson’s disease (PD) significantly impacts patients’ quality of life, early detection remains challenging. Recent advances in magnetic resonance imaging analysis have enabled detailed examination of subcortical structures. This study aimed to investigate subtle changes in specific subregions of the amygdala, thalamus, and hypothalamus in PD patients before they developed cognitive decline. Magnetic resonance imaging data of 163 participants (97 healthy controls [HC], 45 PD patients with normal cognition [PDNC], and 21 PD patients who show cognitive impairment [PDCI]) from the Parkinson’s Progression Markers Initiative database were analyzed. Detailed subregional analyses of brain structures were performed. Cognitive function was assessed using the Montreal Cognitive Assessment and domain-specific tests. The PDCI group exhibited significantly lower intracranial occupancy rates in specific subregions of the amygdala, thalamus, and hypothalamus than the HC group; however, these changes did not correlate significantly with cognitive test scores. Conversely, significant structural changes were observed in extensive cortical regions, subcortical gray matter areas, and white matter areas, which correlated with various cognitive functions including memory, attention, executive function, and visuospatial abilities. Nevertheless, no significant associations were found between changes in individual brain regions and the risk of mild cognitive impairment progression. This study elucidates early brain structural changes associated with cognitive decline in PD. While structural alterations were observed in the amygdala, thalamus, and hypothalamus, widespread cortical changes demonstrated stronger associations with cognitive decline. These findings suggest that cognitive impairment in PD results from extensive cortical network alterations rather than changes in specific subcortical regions. This insight emphasizes the need for a comprehensive approach, considering multiple brain regions and their interactions, in early diagnosis and intervention strategies for PD-related cognitive impairment.
Structural Insights into the Assembly and Regulation of 2’-ORNA Methylation by SARS-CoV-2 nsp16/nsp10
Authors: Misra Anurag , Rahisuddin R. , Parihar Manish , Arya Shailee , Viswanathan Thiruselvam , Jackson Nathaniel , Qi Shan , Chan Siu-Hong , Harris Reuben S. , Martinez-Sobrido Luis , Gupta Yogesh K. 
Published: December 2024

Abstract2’-O-ribose methylation of the first transcribed base (adenine or A1in SARS-CoV-2) of viral RNA mimics the host RNAs and subverts the innate immune response. How nsp16, with its obligate partner nsp10, assembles on the 5’-end of SARS-CoV-2 mRNA to methylate the A1has not been fully understood. We present a ∼ 2.4 Å crystal structure of the heterotetrameric complex formed by the cooperative assembly of two nsp16/nsp10 heterodimers with one 10-mer Cap-1 RNA (product) bound to each. An aromatic zipper-like motif in nsp16 and the N-terminal regions of nsp10 and nsp16 orchestrate an oligomeric assembly for efficient methylation. The front catalytic pocket of nsp16 stabilizes the upstream portion of the RNA while the downstream RNA remains unresolved, likely due to its flexibility. An inverted nsp16 dimer extends the positively charged surface area for longer RNA to influence the catalysis. Additionally, a non-specific nucleotide-binding pocket on the backside of nsp16 plays a critical role in catalysis, further contributing to its enzymatic activity.
The inhibitory effects of Remodelin on murine myoblasts differentiation
Authors: Sian Veronica , Hentschel Andreas , Sarparanta Jaakko , Roos Andreas , Jonson Per Harald , Gayathri Swethaa Natraj , Mai Antonello , Rotili Dante , Altucci Lucia , Udd Bjarne , Savarese Marco , Nebbioso Angela 
Published: December 2024

SummaryMyoblasts differentiation is a highly regulated and complex process leading to the formation of fused and aligned mature myotubes. Growing interest in the role of epigenetics in muscle differentiation has highlighted epi-modulators as crucial regulators of this process. Ourin vitrostudy aimed to explore the potential effects of Remodelin, a selective inhibitor of the acetyltransferase Nat10, on myoblasts differentiation.We cultivated and differentiated murine C2C12 myoblasts on ultra-compliant gelatin for up to 16 days, and treated them with Remodelin. We used confocal microscopy, together with RNAseq and proteomics analyses, to examine the impact of Remodelin on myotube formation.Remodelin impaired myotube organization and maturation, and proper morphology compared to untreated cells. Additionally, no significant twitching was observed upon Remodelin treatment. Intersection of transcriptomics and proteomics analyses confirmed that Remodelin effectively slowed myotube formation. Overall, these results suggest that Remodelin broadly affects the regulatory networks involved in skeletal muscle differentiation.
Chemical degradation identified Human p38-MAPK as a host target to combat parasitic infections
Authors: Singhal Jhalak , Rawat Neha , Bansal Ruby , Srivastava Pallavi , Peer Gajala Deethamvali Ghouse , Pandey Ramendra Pati , Ranganathan Anand , Singh Shailja 
Published: December 2024

SummaryThe interplay between host and parasite determines parasite burden and disease outcome. Parasite exploits host signaling pathways like p38-MAPK for its survival and pathogenesis. NR-7h, a proteolysis-targeting chimera (PROTAC) targeting human p38-MAPK was used to assess p38-MAPK’s role inLeishmania donovaniandPlasmodium falciparuminfection in their respective hosts. NR-7h degraded host p38-MAPK in a time- and dose-dependent manner. Degradation of host p38-MAPK by NR-7h reduced parasite load in host cells dose-dependently, implicating the role of p38-MAPK in parasite survival. The modulation of cytokine profiling and oxidative burst upon NR-7h mediated degradation of host p38-MAPK was further correlated with parasite death. The synergistic effect of host p38-MAPK degradation by NR-7h with Amphotericin B enhances the efficacy of parasite-directed therapy. This study underscores the importance of host p38-MAPK forL. donovaniandP. falciparumprogression and highlights NR-7h’s potential in antiparasitic therapy by targeting this pathway.
The ‘Janus A’ gene encodes a polo-kinase whose loss creates a dorsal/ventral intracellular homeosis in the ciliate,Tetrahymena
Authors: Cole Eric S. , Maier Wolfgang , Huynh Huy Vo , Reister Benjamin , Sowunmi Deborah Oluwabukola , Chukka Uzoamaka , Lee Chinkyu , Gaertig Jacek 
Published: December 2024

AbstractGenetic studies on the protist,Tetrahymena thermophilaprovide a glimpse into the unexpectedly rich world of intracellular patterning that unfolds within the ciliate cell cortex. Ciliate pattern studies provide a useful counterpoint to animal models of pattern formation in that the unicellular model draws attention away from fields of cells (or nuclei) as the principal players in the metazoan pattern paradigm, focusing instead on fields of ciliated basal bodies serving as sources of positional information. In this study, we identifyJANA, a Polo kinase ofTetrahymena, that serves as an important factor driving global, circumferential pattern. Loss of function of JanA results in global, mirror-duplication of ventral organelles on the dorsal surface: a kind of intracellular homeosis that has been named the ‘janus’ phenotype. Gain of function (over-expression) reduces or even eliminates cortical organelles within the ventral ‘hemi-cell’. GFP-tagging reveals that JanA decorates basal bodies predominantly within the left-dorsal hemi-cell. These results led us to propose a model in which the default state of cortical patterning is a mirror-image assemblage of cortical organelles including oral apparatus, contractile vacuole pores and cytoproct. JanA normally suppresses organelle assembly in the dorsal hemi-cellular cortex, resulting in a simple, ventral assemblage of these organelles, a ‘half-pattern’ as it were. PLK inhibitors produce a janus phenocopy, but reveal other unanticipated roles for PLK activities involving more local patterning events that control organelle dimensions and organization. We discuss results in light of metazoan studies in which PLK activity links cell cycle control to intracellular symmetry breaking.
Inferring Nonlinear Dynamics of Cell Migration
Authors: Zadeh Pedrom , Camley Brian A. 
Published: December 2024

The motility of eukaryotic cells is strongly influenced by their environment, with confined cells often developing qualitatively different motility patterns from those migrating on simple two-dimensional substrates. Recent experiments, coupled with data-driven methods to extract a cell's equation of motion, showed that cancerous MDA-MB-231 cells persistently hop in a limit cycle when placed on two-state adhesive micropatterns (two large squares connected by a narrow bridge), while they remain stationary on average in rectangular confinements. In contrast, healthy MCF10A cells migrating on the two-state micropattern are bistable, i.e., they settle into either basin on average with only noise-induced hops between the two states. We can capture all these behaviors with a single computational phase field model of a crawling cell, under the assumption that contact with nonadhesive substrate inhibits the cell front. Our model predicts that larger and softer cells are more likely to persistently hop, while smaller and stiffer cells are more likely to be bistable. Other key factors controlling cell migration are the frequency of protrusions and their magnitude of noise. Our results show that relatively simple assumptions about how cells sense their geometry can explain a wide variety of different cell behaviors, and show the power of data-driven approaches to characterize both experiment and simulation.

Published by the American Physical Society
2024
The role of leadership, continuous improvement and benchmarking on organizational performance: the mediating mechanism of EOC
Authors: Al-Dhaafri Hassan Saleh , Alosani Mohammed Saleh 
Published: December 2024

PurposeThe main purpose of this study is to examine the collective effect of leadership, continuous improvement and benchmarking on organizational performance. In addition, the study also investigates the intervening mechanism of EOC as a mediator between leadership, continuous improvement and benchmarking from one side and organizational performance on the other side.Design/methodology/approachHypotheses for testing have been generated using primary data gathered through a survey questionnaire. A total of 355 questionnaires were returned from amongst 565 when data was gathered from the Dubai police organization. The data was analyzed using the Structural Equation Modelling (SEM) method and SmartPLS.FindingsMost of the hypotheses in the study’s model were found to have a significant effect on organizational performance. Statistical findings using SEM-PLS also confirmed the mediating role of EOC as a mechanism between leadership, continuous improvement, benchmarking and organizational performance.Practical implicationsFindings reported many valuable implications. The study has theoretical implications to close the gap in the existing body of knowledge and practical implications to consider the study’s variables to enhance the overall performance through considering entrepreneurial culture as an intervening mechanism.Originality/valueThe collective role of leadership, continuous improvement, benchmarking, EOC and organizational performance is studied as one of the most important empirical studies which bring original contribution to the existing body of knowledge.