bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontopolar cortex stimulation induces prolonged disruption to counterfactual processing: insights from altered local field potentials
Authors: Ainsworth Matthew , Galeazzi Juan M. , Pedreira Carlos , Stokes Mark G. , Buckley Mark J. 
Published: November 2024

AbstractFrontopolar cortex (FPC) is a large, anterior sub-region of prefrontal cortex found in both humans and non-human primates (NHPs) and is thought to support monitoring the value of switching between alternative goals. However, the neuronal mechanisms underlying this function are unclear. Here we used multielectrode arrays to record the local field potentials (LFPs) in the FPC of two macaques performing a Wisconsin Card Sorting Test analogue and found that bursts of gamma and beta in FPC tracked counterfactual not current rule value. Moreover, we show that brief high-frequency microstimulation to a single trial causally affects both LFP activity in FPC, as well as rule-guided decision-making across successive trials. Following stimulation of FPC we observed reduced exploration of the counterfactual rule pre-rule-change, as well as a delayed adaptation to the newly relevant following post-rule-change. A similar, multi-trial time-course disturbance to beta and gamma activity within FPC was also induced following single-trial microstimulation. These findings conclusively link neuronal activity in FPC with behavioural monitoring of the value of counterfactual rules and provide neural mechanistic insights into how FPC supports rule-based decision-making.Significance statementIncreasing evidence from human and non-human primates has prompted theories linking FPC with the control of exploration during decision-making. However, it is current unclear how the neuronal activity within frontal pole supports exploratory decision-making processes. Here we show that rhythmic activity, in the beta and gamma bands, recorded from FPC is correlated both with outcome of the previous choice, and the value of switching to an alternative choice. Furthermore, we show that disrupting beta and gamma activity within FPC causally influences exploratory decision-making: initially decreasing exploration before impairing adaptation to abstract rule changes. Together these findings provide the first mechanistic insight into how the neuronal activity within FPC can support exploratory behaviour.
Growth rate regulates RNA polymerase II transcription elongation inSaccharomyces cerevisiae
Authors: Garrido-Godino A.I. , González R. , Martín-Expósito M. , Chávez S. , Pérez-Ortín J.E. , Navarro F. 
Published: November 2024

ABSTRACTCells must adapt to changing environmental conditions to maintain their fitness and to compete with other genotypes during the natural selection process. The growth rate (GR) is a determining factor in this competition, and it influences gene expression. Some genes increase mRNA levels, while others decrease with the GR. mRNA levels depend on the dynamic balance between their synthesis by RNA polymerase II and their degradation rates. RNA polymerase I and III are also influenced by the GR because they transcribe protein synthesis machinery required to make proteins that increase cell mass during growth. Although RNA levels have been extensively studied in relation to the GR in many organisms, synthesis and degradation rates have, however, been much less investigated. In a previous work, we found a positive correlation between RNA polymerase (RNA pol) II transcription and mRNA degradation with GRs in yeast in batch cultures. Here we extend our study under constant growth conditions in a chemostat and find that overall chromatin-associated RNA pol II levels increase in parallel with the GR. This increase appears to involve the accumulation of partially dephosphorylated RNA pol II with a greater tendency to backtracking, which suggests that the GR regulates RNA pol II-dependent transcription at the elongation level. RNA pol I also increases its association with chromatin with the GR, which confirms the general dependence of at least RNA pol I and II transcription on the GR.
Structural Insights into Broad-Range Polyphosphate Kinase 2-II Enzymes Applicable for Pyrimidine Nucleoside Diphosphate Synthesis
Authors: Kuge Marco , Keppler Michael , Friedrich Florian , Saleem-Batcha Raspudin , Winter Juliana , Prucker Isabel , Germer Philipp , Gerhardt Stefan , Einsle Oliver , Jung Manfred , Jessen Henning J. , Andexer Jennifer N. 
Published: November 2024

AbstractPolyphosphate kinases (PPK) play crucial roles in various biological processes, including energy storage and stress responses, through their interaction with inorganic polyphosphate (polyP) and the intracellular nucleotide pool. Members of the PPK family 2 (PPK2s) catalyse polyP-consuming phosphorylation of nucleotides. In this study, we characterised two PPK2 enzymes fromBacillus cereus(BcPPK2) andLysinibacillus fusiformis(LfPPK2) to investigate their substrate specificity and potential for selective nucleotide synthesis. Both enzymes exhibited a broad substrate scope, selectively converting over 85% of pyrimidine nucleoside monophosphates (NMPs) to nucleoside diphosphates (NDPs), while nucleoside triphosphate (NTP) formation was observed only with purine NMPs. Preparative enzymatic synthesis of cytidine diphosphate (CDP) was applied to achieve an yield of 49%. Finally, structural analysis of five crystal structures ofBcPPK2 andLfPPK2 provided insights into their active sites and substrate interactions. This study highlights PPK2-II enzymes as promising biocatalysts for the efficient and selective synthesis of pyrimidine NDPs.
Sex chromosomes shape the transcriptional landscape of the preimplantation mouse embryo
Authors: Snell Daniel M. , Varsally Wazeer , Courtois Aurélien , Menchero Sergio , Munusamy Prabhakaran , Rietdijk Richelle , Ojarikre Obah A. , Strohbuecker Stephanie , Kaya Haskan , Sangrithi Mahesh N. , Turner James M.A. 
Published: November 2024

AbstractSex chromosomes are emerging as key regulators of adult health and disease in males (XY) and females (XX), but their impact on embryo development is poorly understood. Using single-cell RNA sequencing (scRNA-seq) on wild type and aneuploid mouse embryos, we show that sex chromosomes significantly shape the preimplantation embryo transcriptional landscape. A hierarchy of effects are identified, distinctly mediated by the Y chromosome, the dosage of X chromosomes, X-chromosome imprinting, and byXist, the non-coding RNA that initiates X-inactivation. The sex chromosomes have strongtranseffects on autosomal gene expression throughout preimplantation development. The Y chromosome has an unexpectedly pronounced impact on the trophectoderm, the precursor of the placenta, and this property is shared with genes expressed from the inactive X chromosome. The paternal and maternal X chromosomes differentially promote preimplantation growth, and we identify multiple novel candidate X-linked imprinted genes mediating this effect. Our findings show that sex chromosomes impact the embryo from the beginning of life, long before the appearance of overt sex differences.
Cortical neural activity during responses to mechanical perturbation: Effects of hand preference and hand used
Authors: Hooks Kevin , Kiani Kimia , Fu Qiushi 
Published: November 2024

ABSTRACTHandedness, as measured by self-reported hand preference, is an important feature of human behavioral lateralization that has often been associated with hemispheric specialization. We examined the extent to which hand preference and whether the dominant hand is used or not influence the motor and neural response during voluntary unimanual corrective actions. The experimental task involved controlling a robotic manipulandum to move a cursor from a center start point to a target presented above or below the start. In some trials, a mechanical perturbation of the hand was randomly applied by the robot either consistent or against the target direction, while electroencephalography (EEG) was recorded. Twelve left-handers and ten right-handers completed the experiment. Left-handed individuals had a greater negative peak in the frontal event-related potential (ERP) than right-handed participants during the initial response phase (N150) than right-handed individuals. Furthermore, left-handed individuals showed more symmetrical ERP distributions between two hemispheres than right-handed individuals in the frontal and parietal regions during the late voluntary response phase (P390). To the best of our knowledge, this is the first evidence that demonstrates the differences in the cortical control of voluntary corrective actions between left-handers and right-handers.
Rapid folding of nascent RNA regulates eukaryotic RNA biogenesis
Authors: Schärfen Leonard , Vock Isaac W. , Simon Matthew D. , Neugebauer Karla M. 
Published: November 2024

SummaryAn RNA’s catalytic, regulatory, or coding potential depends on RNA structure formation. Because base pairing occurs during transcription, early structural states can govern RNA processing events and dictate the formation of functional conformations. These co-transcriptional states remain unknown. Here, we develop CoSTseq, which detects nascent RNA base pairing within and upon exit from RNA polymerases (Pols) transcriptome-wide in living yeast cells. By monitoring each nucleotide’s base pairing activity during transcription, we identify distinct classes of behaviors. While 47% of rRNA nucleotides remain unpaired, rapid and delayed base pairing – with rates of 48.5 and 13.2 kb-1of transcribed rDNA, respectively – typically completes when Pol I is only 25 bp downstream. We show that helicases act immediately to remodel structures across the rDNA locus and facilitate ribosome biogenesis. In contrast, nascent pre-mRNAs attain local structures indistinguishable from mature mRNAs, suggesting that refolding behind elongating ribosomes resembles co-transcriptional folding behind Pol II.
Adolescent-like Processing of Behaviorally Salient Cues in Sensory and Prefrontal Cortices of Adult Preterm-Born Mice
Authors: McCoy Emily , Pendala Vyshnavi , Fariborzi Mona , Demir Lara Y. , Buell Olivia , Fedde Samuel , Stinger Jacqueline , Elbaum Luciano , Holsworth Troy D. , Amenyo-Awude Phillip , Ribic Adema 
Published: November 2024

AbstractPreterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it is unclear how prematurity impacts circuits that support these functions. To address this, we trained adult mice born a day early (preterm mice) on a visual discrimination task and found that they commit more errors and fail to achieve high levels of performance. Usingin vivo electrophysiology, we found that the neurons in the primary visual cortex (V1) and the V1-projecting prefrontal anterior cingulate cortex (ACC) are hyper-responsive to the reward, reminiscent of cue processing in adolescence. Moreover, the non-rewarded cue fails to robustly activate the V1 and V1-projecting ACC neurons during error trials, in contrast to prefrontal fast-spiking (FS) interneurons which show elevated error-related activity, suggesting that preterm birth impairs the function of prefrontal circuits for error monitoring. Finally, environmental enrichment, a well-established paradigm that promotes sensory maturation, failed to improve the performance of preterm mice, suggesting limited capacity of early interventions for reducing the risk of cognitive deficits after preterm birth. Altogether, our study for the first time identifies potential circuit mechanisms of cognitive atypicalities in the preterm population and highlights the vulnerability of prefrontal circuits to advanced onset of extrauterine experience.
High-resolution profiling reveals coupled transcriptional and translational regulation of transgenes
Authors: Peterman Emma L. , Ploessl Deon S. , Love Kasey S. , Sanabria Valeria , Daniels Rachel F. , Johnstone Christopher P. , Godavarti Diya R. , Kabaria Sneha R. , Oakes Conrad G. , Pai Athma A. , Galloway Kate E. 
Published: November 2024

AbstractConcentrations of RNAs and proteins provide important determinants of cell fate. Robust gene circuit design requires an understanding of how the combined actions of individual genetic components influence both mRNA and protein levels. Here, we simultaneously measure mRNA and protein levels in single cells using HCR Flow-FISH for a set of commonly used synthetic promoters. We find that promoters generate differences in both the mRNA abundance and the effective translation rate of these transcripts. Stronger promoters not only transcribe more RNA but also show higher effective translation rates. While the strength of the promoter is largely preserved upon genome integration with identical elements, the choice of polyadenylation signal and coding sequence can generate large differences in the profiles of the mRNAs and proteins. We used long-read direct RNA sequencing to characterize full-length mRNA isoforms and observe remarkable uniformity of mRNA isoforms from the transgenic units. Together, our high-resolution profiling of transgenic mRNAs and proteins offers insight into the impact of common synthetic genetic components on transcriptional and translational mechanisms. By developing a novel framework for quantifying expression profiles of transgenes, we have established a system for comparing native and synthetic gene regulation and for building more robust transgenic systems.
Functional Dichotomy of Orbitofrontal Cortex and Anterior Cingulate Cortex Subregions in Decision-Making and Brain-Body Regulation
Authors: Papageorgiou G.K. , Gibson D.J. , Amemori K. , Schwerdt H.N. , Naim M. , Wang M.C. , Yoshida T. , Sharma J. , Upadhyay U. , Yang G.R. , Graybiel A.M. 
Published: November 2024

AbstractMood disorders are associated with complex disruptions in brain networks, including those associated with the orbitofrontal cortex (OFC) and pregenual anterior cingulate cortex (pACC). The functional contribution of the caudal OFC (cOFC) has remained largely unexplored. We investigated the functions of the cOFC and pACC in macaques performing an approach-avoidance task by the combination of multimodal recordings and electrical microstimulation (EMS) of the cOFC. We assessed neural, autonomic and behavioral responses. We found the cOFC to be sensitive to both positive and negative stimuli, whereas the pACC was singificantly more active during aversive outcomes. EMS of the cOFC increased avoidance behavior, suggesting a causal role for the OFC subdivision in cost-benefit decision-making. Physiological measurements were positively correlated with behavioral patterns, emphasizing body-brain synchronization during emotionally significant decision-making. We suggest that the cOFC contributes to inducing pessimistic states, thereby making its dysfunction a potential contributor to the etiology of mood disorders.
Codon optimality modulates cellular stress and innate immune responses triggered by exogenous RNAs
Authors: Seephetdee Chotiwat , Kiss Daniel L. 
Published: November 2024

AbstractThe COVID-19 mRNA vaccines demonstrated the power of mRNA medicines. Despite advancements in sequence design, evidence regarding the preferential use of synonymous codons on cellular stress and innate immune responses is lacking. To this end, we developed a proprietary codon optimality matrix to re-engineer the coding sequences of three luciferase reporters. We demonstrate that optimal mRNAs elicited dramatic increases in luciferase activities compared to non-optimal sequences. Notably, transfecting an optimal RNA affects the translation of other RNAs in the cell including control transcripts in dual luciferase assays. This held true in multiple cell lines and for an unrelated reporter. Further, non-optimal mRNAs preferentially activated innate immune pathways and the phosphorylation of the translation initiation factor eIF2α, a central event of the integrated stress response. Using nucleoside-modified or circular RNAs partially or fully abrogated these responses. Finally, we show that circularizing RNAs enhances both RNA lifespan and durability of protein expression. Our results show that RNA sequence, composition, and structure all govern RNA translatability. However, we also show that RNA sequences with poor codon optimality are immunogenic and induce cellular stress. Hence, RNA sequence engineering, chemical, and topological modifications must all be combined to elicit favorable therapeutic outcomes.
Crystal structure of glutamyl-tRNA synthetase from Helicobacter pylori
Authors: Davis Dylan E. , Ayanlade Jesuferanmi P. , Laseinde David T. , Subramanian Sandhya , Udell Hannah , Lorimer Donald J. , Dranow David M. , Edwards Thomas E. , Myler Peter J. , Asojo Oluwatoyin A. 
Published: November 2024

Helicobacter pylori is one of the most common bacterial infections; over two-thirds of the world's population is infected by early childhood. Persistent H. pylori infection results in gastric ulcers and cancers. Due to drug resistance, there is a need to develop alternative treatments to clear H. pylori. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducts structure–function analysis of potential therapeutic targets from H. pylori. Glutamyl-tRNA synthetase (GluRS) is essential for tRNA aminoacylation and is under investigation as a bacterial drug target. The SSGCID produced, crystallized and determined the apo structure of H. pylori GluRS (HpGluRS). HpGluRS has the prototypical bacterial GluRS topology and has similar binding sites and tertiary structures to other bacterial GluRS that are promising drug targets. Residues involved in glutamate binding are well conserved in comparison with Pseudomonas aeruginosa GluRS (PaGluRS), which has been studied to develop promising new inhibitors for P. aeruginosa. These structural similarities can be exploited for drug discovery and repurposing to generate new antibacterials to clear persistent H. pylori infection and reduce gastric ulcers and cancer.
Convergence theory of efficient parametric iterative methods for solving the Yang-Baxter-like matrix equation
Authors: Erfanifar Raziyeh , Sayevand Khosro , Hajarian Masoud 
Published: November 2024

PurposeIn this study, we present a novel parametric iterative method for computing the polar decomposition and determining the matrix sign function.Design/methodology/approachThis method demonstrates exceptional efficiency, requiring only two matrix-by-matrix multiplications and one matrix inversion per iteration. Additionally, we establish that the convergence order of the proposed method is three and four, and confirm that it is asymptotically stable.FindingsIn conclusion, we extend the iterative method to solve the Yang-Baxter-like matrix equation. The efficiency indices of the proposed methods are shown to be superior compared to previous approaches.Originality/valueThe efficiency and accuracy of our proposed methods are demonstrated through various high-dimensional numerical examples, highlighting their superiority over established methods.
Environmental preferences in architecture based on personality types
Authors: Sarrafzadeh Ahmad , Gharehbaglou Minou 
Published: November 2024

Purpose
Individuals show different environmental preferences, often influenced by their personality types. However, instances arise where the alignment of an individual’s personality and the architectural environment disappears, resulting in a mismatch. Consequently, the purpose of this study considers the urgent need to acknowledge and understand the complex interplay between architecture and individual personality traits.

Design/methodology/approach
The research method is based on the correlation between the variables, which is calculated by the significant assessment of the sample population and with SmartPLS. Finally, the findings and results of the research in relation to personality components and architectural aspects indicate the existence of a relationship. In the end, this study establishes correlations among variables and conclusions are drawn through systematic logical deductions.

Findings
The research findings underscore a compelling relationship between distinct personality components and various architectural facets. Furthermore, psychological cohesiveness within distinct social cohorts emerges as a pivotal factor influencing the relationship between individuals and architecture. In this regard, the main aspects of environmental preferences (surprise, cryptic, etc.) and personality types (neuroticism, extroversion, etc.) based on their significance and the factors affecting it in sub-components, create direct or indirect relationships. Additionally, the determination of the relationships created in each of these components is specified based on Image 12, and the path of creating architectural patterns can be considered according to that.

Originality/value
The results of the research show that the correlation between personality and physical components in different social groups is an effective issue in the relationship between human and the environment. It can also be considered as a factor for improving the quality of architectural design and creating a favorable cultural atmosphere in the environment. This issue has caused a connection between architecture and human personality, which creates the ground for improving the relationship between them. Also, architecture is placed by adapting to the personality and psychological needs of people and has an effective role in the quality of their relationships in organizing and expanding the environment.
Burnout in healthcare: can job autonomy heal, or does context hold the key?
Authors: Reyes-Luján Juanjo , Cruz-Ortiz Valeria , Antino Mirko , Salanova Marisa 
Published: November 2024

PurposeThis study investigates the relationship between job autonomy and burnout among healthcare professionals, focusing on two key contextual elements that moderate this relationship: role ambiguity and workers’ age.Design/methodology/approachEmploying an integrative approach, this research combines the Job Demands-Resources model with the lifespan developmental framework. A multilevel analysis was conducted on a sample of 1,232 hospital workers, nested within 74 units, to examine the relationships between job autonomy and burnout across teams with varying levels of aggregated role ambiguity, incorporating the factor of workers’ age.FindingsThe results indicate significant interaction effects between job autonomy, age and role ambiguity in relation to burnout. Job autonomy is associated with lower levels of burnout in contexts of moderate role ambiguity. In contrast, in highly uncertain contexts, job autonomy proves more beneficial for older workers, while it appears to have negative effects on younger workers.Originality/valueThis study enhances our understanding of the complex dynamics between job autonomy and burnout among healthcare professionals by utilizing a multilevel approach to examine the impact of contextual role ambiguity and workers’ age. The multilevel analysis offers original insights into the role of ambiguity, while the integration of two robust theoretical frameworks (i.e. JD-R model and Lifespan framework) provides a solid foundation for contributing to the discussion.