bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular dynamics simulations reveal DNA gate opening mechanisms forM. smegmatistopoisomerase 1A
Authors: Sigdel Deepesh , Mills Maria 
Published: February 2025

ABSTRACTType 1A topoisomerases relax torsional strain in DNA via a strand passage mechanism in which a protein mediated DNA gate must open during the enzyme’s catalytic cycle. This gate-open conformational state of the enzyme has been challenging to observe via experimental methods. In this study, we first used equilibrium Molecular Dynamics simulations to probe the structural properties of the gate closed state for the DNA-free apo system and a system with a ssDNA bound at the DNA binding site. For both systems, we followed the equilibrium simulations with Umbrella Sampling simulations. Umbrella sampling allowed us to bias the protein to adopt a gate-open state to study the properties of this conformation, as well as the pathways leading to it. We observed that several electrostatic interactions contribute to the closed-state stability of the protein which were broken during the gate opening. The gate opening comprised of three major domain motions that were determined from simulation trajectories and Principal Component Analysis. Finally, umbrella sampling results combined with the Weighted Histogram Analysis Method allowed us to reconstruct the free energy profiles of gate opening for all simulations.SIGNIFICANCEMulti-drug resistant bacterial strains necessitate newer ways of targeting bacteria. Type 1A topoisomerases are potential anti-bacterial drug targets. Current strategies are to either block the protein binding to DNA or prevent the cut DNA being religated during the catalytic cycle. A possible alternative to these methods would be to trap the protein at an open conformation. Structural information about the transient open state is crucial to this approach. Results of this study provide mechanistic details of gate opening. This information furthers the understanding of the topoisomerase catalytic cycle which will aid in anti-topoisomerase drug design efforts.
The Opposing Roles of H2A and H2B Ubiquitination on Nucleosome Dynamics Revealed by Molecular Simulations
Authors: Baweja Lokesh , Wereszczynski Jeff 
Published: February 2025

AbstractNucleosome ubiquitination at lysine 119 of histone H2A (H2AK119Ub) and lysine 120 of histone H2B (H2BK120Ub) are prominent post-translational modifications with opposing roles in chromatin regulation. While H2AK119Ub is associated with transcriptional repression, H2BK120Ub promotes activation, yet the structural mechanisms underlying these effects remain poorly understood due to experimental limitations. To address this, we employed microsecond-scale all-atom molecular dynamics and coarse-grained simulations to investigate the impact of ubiquitination at these sites on nucleosome dynamics. Our results reveal that ubiquitin interacts weakly with DNA in both cases but exhibits higher affinity in H2AK119Ub. Notably, H2AK119Ub stabilizes the nucleosome by strengthening tetramer-dimer and dimer-dimer interactions, particularly at the L1-L1 loop regions, through long-range contacts. In contrast, H2BK120Ub disrupts these interactions, destabilizing the nucleosome and promoting transitions toward hexasomal and tetrasomal states, as observed in coarse-grained nucleosome folding simulations. These findings suggest that ubiquitination directly modulates nucleosome stability and dynamics in a site-dependent manner, providing a mechanistic framework for how chromatin structure is tuned through post-translational modifications.
The effect of chronic stress and chronic alcohol intake on behavior, brain structure, and functional connectivity in a rat model
Authors: Rasgado-Toledo Jalil , Angeles-Valdez Diego , Carranza-Aguilar César J. , Lopez-Castro Alejandra , Trujillo-Villarreal Luis A. , Medina-Sánchez David , Serrano-Ramirez Mariana S. , Débora Elizarrarás-Herrera A. , Alcauter Sarael , Delint-Ramirez Ilse , Gutierrez Ranier , Devenyi Gabriel A. , Mallar Chakravarty M. , Garza-Villarreal Eduardo A. 
Published: February 2025

AbstractPathological chronic stress is stress exceeding the organism’s ability to cope physiologically, which may act as a risk factor in the onset and relapse of alcohol use disorder. Chronic- restraint stress (CRS) and ethanol intake are independently known to induce changes in brain structure and function, however, their combined effects on neurodevelopment over long periods of time remains largely unexplored. We conducted an in vivo longitudinal rat model with three main goals. 1) to determine if chronic stress increases ethanol intake; 2) to determine the effect of chronic- stress and ethanol intake in behavioral measures, brain structure, and function; and 3) to investigate the effect of sex. This observational study included Wistar rats assigned to four groups: 1) ethanol consumption (EtOH+/CRS-), 2) stress exposure (EtOH-/CRS+), 3) both ethanol and stress exposure (EtOH+/CRS+), and 4) control group (EtOH-/CRS-). Our results showed that chronic stress did not affect ethanol intake but led to reduced body weight gain, elevated corticosterone levels, and impaired recognition memory. Structural MRI revealed that both exposures produced additive brain volume changes in regions such as the olfactory bulb, orbitofrontal cortex, caudate-putamen, hippocampus, and cerebellum. Functional connectivity analysis using network-based statistics identified disrupted cortical-subcortical connections. Results found here were sex-dependent in terms of volumetric changes (higher effects on males) and functional connectivity (higher effects on females). Findings suggest sex-dependent mechanisms where both chronic- ethanol intake and stress affect brain plasticity during neurodevelopment. Understanding these region-specific vulnerabilities is crucial for addressing alcohol use disorders and stress-related neuropathology.Graphical abstractCreated with bioRender
TF2TG: an online resource mining the potential gene targets of transcription factors inDrosophila
Authors: Hu Yanhui , Rodiger Jonathan , Liu Yifang , Gao Chenxi , Liu Ying , Qadiri Mujeeb , Veal Austin , Bulyk Martha L. , Perrimon Norbert 
Published: February 2025

AbstractSequence-specific transcription factors (TFs) are key regulators of many biological processes, controlling the expression of their target genes through binding to the cis-regulatory regions such as promoters and enhancers. Each TF has unique DNA binding site motifs, and large-scale experiments have been conducted to characterize TF–DNA binding preferences. However, no comprehensive resource currently integrates these datasets forDrosophila. To address this need, we developed TF2TG (“transcription factor to target gene”), a comprehensive resource that combines bothin vitroandin vivodatasets to link transcription factors (TFs) to their target genes based on TF–DNA binding preferences along with the protein-protein interaction data, tissue-specific transcriptomic data, and chromatin accessibility data. Although the genome offers numerous potential binding sites for each TF, only a subset is actually boundin vivo, and of these, only a fraction is functionally relevant. For instance, some TFs bind to their specific sites due to synergistic interactions with other factors nearby. This integration provides users with a comprehensive list of potential candidates as well as aids users in ranking candidate genes and determining condition-specific TF binding for studying transcriptional regulation inDrosophila.
Evidence accumulation from experience and observation in the cingulate cortex
Authors: Chen Ruidong , Radkani Setayesh , Valluru Neelima , Yoo Seng Bum , Jazayeri Mehrdad 
Published: February 2025

AbstractWe use our experiences to form and update beliefs about the hidden states of the world. When possible, we also gather evidence by observing others. However, how the brain integrates experiential and observational evidence is not understood. We studied the dynamics of evidence integration in a two-player game with volatile hidden states. Both humans and monkeys successfully updated their beliefs while playing the game and observing their partner, though less effectively when observing. Electrophysiological recordings in animals revealed that the anterior cingulate cortex (ACC) integrates independent sources of experiential and observational evidence into a coherent neural representation of dynamic belief about the environment’s state. The geometry of population activity revealed the computational architecture of this integration and provided a neural account of the behavioral asymmetry between experiential and observational evidence accumulation. This work lays the groundwork for understanding the neural mechanisms underlying evidence accumulation in social contexts within the primate brain.
Additive effects on craniofacial development upon conditional ablation of PDGFRαand SHP2 in the mouse neural crest lineage
Authors: Fuhr Daniel , Johnston Jessica , Brooks Elliott P. , Fantauzzo Katherine A. 
Published: February 2025

AbstractBackgroundActivity of the receptor tyrosine kinase PDGFRαand the tyrosine phosphatase SHP2 are critical for vertebrate craniofacial development. We sought to determine the effect of SHP2 binding to PDGFRαvia phenotypic and biochemical analyses of an allelic series of mouse embryos with combined loss of both proteins in the neural crest lineage.ResultsWe demonstrated that SHP2 preferentially binds PDGFRα/αhomodimers among the three PDGFR dimers. Analysis of allelic series mutant embryos revealed increased cell death in the lateral nasal and maxillary processes at E10.5, variably penetrant facial blebbing, facial hemorrhaging, midline clefting and loss of the mandibular region at E13.5, and widespread craniofacial bone and cartilage defects at birth. Further, we showed that loss of SHP2 leads to increased phosphorylation of PDGFRαand the downstream effector Erk1/2 in E10.5 allelic series mutant embryo lysates.ConclusionsTogether, our findings demonstrate additive effects on craniofacial development upon conditional ablation of PDGFRαand SHP2 in the mouse neural crest lineage and indicate that SHP2 may negatively and positively regulate PDGFRαsignaling through distinct mechanisms.
Differential impacts of various bacteria on the health and survival of the sea anemoneExaiptasia diaphana
Authors: Romo Kaitlyn M. , Tran Cawa 
Published: February 2025

AbstractCoral reefs are threatened by rising ocean temperatures associated with climate change, leading to a breakdown of the cnidarian-dinoflagellate symbiosis and growth of pathogenic bacteria. The host response to diverse bacteria can vary from species to species. In this study, the sea anemoneExaiptasia diaphana(commonly referred to as ‘Aiptasia’), a prominent laboratory model for coral-symbiosis research, was used to investigate host responses to three key bacterial species associated with both Aiptasia and corals.Ruegeria mobilis,Vibrio alginolyticus, andAlteromonas macleodiiwere individually inoculated into the seawater of both symbiotic (with dinoflagellates) and aposymbiotic (without dinoflagellates) hosts to determine their effects on host health. Each bacterium was hypothesized to have a different effect on host health— beneficial, pathogenic, or no effect. Various densities of each bacterium were used to assess impacts on host morphology and survival over 14 days at 27°C. Host biomass, protein content, and dinoflagellate abundance (to assess bacterial effects on host bleaching) were examined over 7 days at 27°C in response to an inoculation density of 8×108cells ml-1of each bacterium. When compared to un-inoculated Aiptasia,V. alginolyticusreduced host survival of symbiotic and aposymbiotic hosts, and biomass by 27% and 54% in symbiotic and aposymbiotic Aiptasia, respectively.V. alginolyticusalso diminished dinoflagellate abundance by 20% in symbiotic Aiptasia. In contrast,R. mobilisenhanced survival of symbiotic Aiptasia, biomass by 9%, protein content by 50%, and dinoflagellate abundance by 60%, but had no impacts on aposymbiotic Aiptasia.A. macleodiihad no major effects on host health at all. As a result,V. alginolyticusgenerally has negative impacts on host health, whileR. mobilisappears to be a beneficial bacterium. Moreover, host susceptibility to bacteria is dependent on whether animals have their dinoflagellates to begin with and, therefore, bleached cnidarians may experience more drastic responses to pathogens likeV. alginolyticus, but no benefits from a potential probiotic likeR. mobilis.ImportanceIdentification of specific beneficial microbes is a major contribution to conservation techniques, such as microbiome manipulation, that aim to assist cnidarians in adapting to climate change. However, to maintain these conservation efforts in the long term, moving forward, we must prioritize foundational questions that examine dinoflagellate-bacterial interactions and bacterial-colonization dynamics within the cnidarian host.
Triple antimicrobial combinations with potent synergistic activity againstM. abscessus
Authors: Huang Yanqin , Chiaraviglio Lucius , Bode-Sojobi Ibidunni , Kirby James E. 
Published: February 2025

AbstractSynergy of antimicrobial combinations was tested against contemporaryMycobacteroidesabscessus isolates using 2-D and 3-D checkerboard assays. Triple combinations of omadacycline-azithromycin-clofazimine, tigecycline-azithromycin-clofazimine, omadacycline-azithromycin-linezolid and omadacycline-azithromycin-contezolid demonstrated synergy (FIC ≤ 0.5) against 33%, 31%, 62%, and 66% of isolates, respectively. Notably, in all triple combinations, macrolide resistantM. abscessussubsp.abscessusandM. abscessussubsp.bolletiiisolates were fully sensitized to azithromycin at the FIC index, as were isolates with elevated clofazimine MICs.
Deep-water closure model for surface waves on axisymmetric swirling flows
Authors: Zuccoli Emanuele , Brambley Edward J. , Barkley Dwight 
Published: February 2025

We consider the propagation of linear gravity waves on the free surface of steady, axisymmetric flows with purely azimuthal velocity. We propose a two-dimensional set of governing equations for surface waves valid in the deep-water limit. These equations come from a closure condition at the free surface that reduces the three-dimensional Euler equations in the bulk of the fluid to a set of two-dimensional equations applied only at the free surface. Since the closure condition is not obtained rigorously, it is validated numerically through comparisons with full three-dimensional calculations for vortex flows, including for a Lamb-Oseen vortex. The model presented here overcomes three limitations of existing models: namely, it is not restricted to potential base flows, it does not assume the base flow to have a flat free surface, and it does not require the use of infinite-order differential operators [such as tanh(∇)] in the governing equations. The model can be applied in the case of rapid swirl (large Froude number) where the base free surface is substantially deformed. Since the model contains only derivatives of finite order, it is readily amenable to standard numerical study.

Published by the American Physical Society
2025
Observation of nonreciprocal polarization modulations induced by an intense terahertz electric-field pulse in an electronic-type molecular ferroelectric
Authors: Kubo T. , Miyamoto T. , Takamura N. , Yamamoto M. , Ikeda R. , Sato T. , Okamoto H. 
Published: February 2025

An intense terahertz pulse has the potential to control the polarization of ferroelectrics at the subpicosecond time scale. In some ferroelectrics, it has been reported that irradiation with a terahertz pulse on the order of 100 kV/cm modulates the polarization in a manner proportional to the electric field. If a stronger electric field is applied, it may be possible to alter the polarization nonlinearly or even cause it to disappear. However, such attempts have not been reported to date. In this paper, we aim to nonlinearly control ferroelectric polarization by irradiating an organic molecular compound tetrathiafulvalene-p-chloranil (TTF-CA), a typical electronic-type ferroelectric, with a terahertz pulse having an electric-field amplitude of up to 2.2 MV/cm. When the temperature is reduced, TTF-CA undergoes a neutral () to ionic () phase transition at Tc=81K, and the degree of charge transfer ρ from CA to TTF changes from 0.3 to 0.6. In the phase, it shows the ferroelectricity owing to the collective intermolecular charge transfer at Tc. Therefore, if the -to- conversion is induced by a strong electric field, the ferroelectric polarization P may change significantly. To investigate the changes in ρ and P along the electric-field waveform of the terahertz pulse in the ferroelectric phase of TTF-CA, in this paper, a terahertz pump-optical reflectivity probe and second harmonic generation (SHG) probe measurements are performed. For the terahertz electric-field amplitudes ETHz<0.5MV/cm, the changes in ρ and P are proportional to ETHz. When ETHz>0.5MV/cm is applied parallel to P, the increases in ρ and P tend to become saturated. The increase in is only ∼10% at a maximum electric-field amplitude of 2.2 MV/cm. In contrast, when ETHz is antiparallel to P, the decreases in ρ and P are proportional to ETHz up to 1.5 MV/cm. When ETHz is further increased to values >1.5 MV/cm, a partial -to- conversion occurs via quantum electron tunneling processes, and P decreases in a nonlinear manner. The decrease in reaches ∼30% at 2.2 MV/cm. These nonreciprocal changes in ρ and P are discussed while considering the valence instability characteristic of TTF-CA. Furthermore, several coherent oscillations are observed in the changes of reflectivity and SHG, which reflect the modulations of ρ and P due to molecular vibrations (lattice modes), respectively. A detailed analysis of the amplitudes and phases of these coherent oscillations reveals that a molecular vibration with a frequency of ∼90 cm−1 is driven by changes in ρ induced by a terahertz electric field and modulates P significantly through the changes in the dimeric molecular displacements along the molecular stacking axis, that is, the polarization direction.

Published by the American Physical Society
2025
Why do players continue playing esports? A mixed-method study based on uses and gratifications theory
Authors: Nguyen Dung Minh , Daxauer Georg 
Published: February 2025

PurposeIn the growing esports landscape, understanding esports players’ motivations and behaviors is crucial to academics and practitioners. However, research on what motivates individuals to play esports and their effects on players’ affective engagement and behavioral responses remain limited. Drawing on the uses and gratifications (U&G) theory, this study explores key motivations that drive players to play esports and examines how these factors influence players’ affective engagement and intentions to continue playing.Design/methodology/approachA qualitative study using open-ended essays with 60 Taiwanese esports players was conducted to identify key factors motivating individuals to play esports. Subsequently, a quantitative survey with 328 esports players was undertaken to test the research model using structural equation modeling.FindingsThe qualitative results identified five key motivations (i.e. entertainment, escapism, achievement, self-presentation and social interaction), which were classified into utilitarian, hedonic and social gratifications. The quantitative analysis results revealed that all identified motivations positively influenced two dimensions of affective engagement (i.e. dedication and enthusiasm), which, in turn, led to esports continuance intention.Originality/valueThis study demonstrates the power of the U&G theory in identifying different gratifications associated with esports. Furthermore, by using a mixed-method approach incorporating both qualitative and quantitative techniques, this study offers a fresh perspective on esports-related research. The findings provide practical guidance for game developers and marketers to sustain player engagement, fostering sustainable growth in the esports industry.
Information precarity and microaggressions: how race-based trauma mediates Latinx people’s information practices
Authors: Vasquez Fátima Espinoza , Oltmann Shannon 
Published: February 2025

PurposeThis paper explores the concept of information precarity, tracing some of its foundations to microaggressions and systemic injustices experienced by marginalized populations over time as race-based trauma, which functions as a mediating mechanism affecting the information practices of individuals and communities.Design/methodology/approachWe describe the conceptual background of information precarity, information practices, microaggressions and race-based trauma, then illustrate these concepts through interviews and focus groups from a network of people and organizations helping a Latinx community navigate the COVID crisis.FindingsThe conceptual framework connecting information precarity with microaggressions and race-based trauma provides context and explanation for the information practices of marginalized communities living in information precarity.Research limitations/implicationsThe study primarily explored adverse experiences such as microaggressions, which means that instances where Latinx individuals successfully navigated systemic barriers should be further explored. The study is based on the lived experiences of a specific group of Latinx individuals from a particular geographic area. Thus, findings may not be generalizable to all Latinx populations or other marginalized groups. This study’s findings suggest that efforts to improve information access must go beyond providing resources or making more policies. We recommend actions. Recognizing that race-based trauma affects how people engage with information highlights the importance of building and maintaining trust with marginalized communities.Practical implicationsIn this study, we suggest actions. Recognizing that race-based trauma affects how people engage with information highlights the importance of building and maintaining trust with marginalized communities. Culturally sensitive outreach strategies such as support networks, community advisory boards, cultural liaisons or information brokers are crucial. Institutions can and should create environments where individuals feel safe to seek and share information with more personalized or community-specific approaches and a long-term commitment to information accessibility.Originality/valueFirst, it illustrates the mechanisms through which precarity persists by showing how microaggressions are a systemic barrier that significantly shapes information practices and perpetuates vulnerability. Second, we demonstrated that race-based trauma is a mediating factor in information precarity, highlighting how racism emerges tangibly in everyday interactions as a mediating factor in information practices. Third, we show that information precarity, mediated by race-based trauma, can result in an information practice of avoidance as a protective mechanism to steer clear of unfair treatment and racist behavior.