bluuebunny/crossref_metadata_2025_split huggingface dataset:
FUS post-transcriptional splicing is autoregulated via RNA condensation with therapeutic potential for ALS-FUS
Authors: Huang Wan-Ping , Kumar Vedanth , Yap Karen , An Haiyan , John Sabin J. , Hodgson Rachel E. , Avila Anna Sanchez , Day Emily , Ellis Brittany C.S. , Chung Tek Hong , Lord Jenny , Müller-McNicoll Michaela , Makeyev Eugene V. , Shelkovnikova Tatyana A. 
Published: February 2025

AbstractMutations in theFUSgene cause aggressive and often juvenile forms of amyotrophic lateral sclerosis (ALS-FUS). In addition to mRNA, theFUSgene gives rise to a partially processed RNA with retained introns 6 and 7. We demonstrate that these FUSint6&7-RNAs form nuclear condensates scaffolded by the highly structured intron 7 and associated with nuclear speckles. Using hybridization-proximity labelling proteomics, we show that the FUSint6&7-RNA condensates are enriched in splicing factors and the m6A reader YTHDC1. These ribonucleoprotein structures facilitate post-transcriptional FUS splicing and depend on m6A/YTHDC1 for their maintenance. FUSint6&7-RNAs become hypermethylated in cells expressing mutant FUS, leading to their enhanced condensation and consequently, splicing. We further demonstrate that FUS protein is repelled by m6A. Thus, ALS-FUS mutations may cause an abnormal activation of FUS post-transcriptional splicing via altered RNA methylation. Strikingly, ectopic expression of FUS intron 6&7 sequences dissolves the endogenous FUSint6&7-RNA condensates, downregulating FUS mRNA and protein. Overall, we describe an RNA condensation-dependent mechanism regulating FUS splicing that can be harnessed for developing new therapies.
The 3’ Region of the ZPA Regulatory Sequence (ZRS) is required for activity and contains a critical E-box
Authors: Ball Kathryn F. , Manu Stephen , Underhill Abbie K. , Rudd Sarah R. , Malone Madison M. , Amoah Japhet , Cooper Allen M. , Pira Charmaine U. , Oberg Kerby C. 
Published: February 2025

1AbstractBackgroundDuring development, Hand2 and Hoxd13 transcription factors (TFs) regulate Sonic hedgehog (Shh) expression in the zone of polarizing activity (ZPA) in the distal posterior limb mesoderm. The ZPA regulatory sequence (ZRS) is a conserved, limb-specific enhancer that controls Shh expression. The ZRS can be divided into 5’, central, and 3’ subdomains, each with an E-box site that can bind basic helix-loop-helix (bHLH) TFs like Hand2. In addition, two Hoxd13 sites are present in the 5’ and central subdomains. Hand2 purportedly binds the ZRS through the central E-box, and both Hand2 and Hoxd13 have been shown to activate the ZRSin vitro. We hypothesized that the central E-box was required for activity, while the other E-boxes and Hoxd13 sites localize ZRS activity to the distal posterior limb mesoderm.MethodsTo identify the functional role of each subdomain, we generated three ZRS fragments (5’, central, and 3’) and combined fragment constructs to test subdomain collective contributions. Additionally, we disrupted the five binding sites, alone or in concert, using site-directed mutagenesis. All ZRS constructs were cloned into a GFP reporter and evaluated in anin vivochicken limb bioassay. We validated our findings using select ZRS constructs in transgenic mice.ResultsWe found that the 3’ fragment was necessary for ZRS activity, while the 5’ and central fragments had no activity alone or when combined. However, combining the 3’ fragment with the 5’ fragment restored robust activity. Further, mutation of all five binding sites markedly reduced ZRS activity. Reinstating each of the Hoxd13 sites restored focal activity, while restoring the 5’ and central E-boxes had little effect. However, the 3’ E-box proved sufficient for robust activity even in the absence of the other four binding sites.ConclusionsOur data indicate that the ZRS 3’, not the central, subdomain is necessary for activity and contains the 3’ E-box that Hand2 likely uses to induce Shh expression, while the 5’ and central E-boxes appear to be inhibitory. Our data also suggest that the Hoxd13 binding sites promote localized activity within the ZPA.
Aerobic exercise decreases the number and transcript expression of inflammatory M1 macrophages and CD8+ T cells in the epicardial adipose tissue of female pigs
Authors: Ahmad Irshad , Gupta Shreyan , Thomas Micah , Cai James J. , Heaps Cristine L. , Newell-Fugate Annie E. 
Published: February 2025

AbstractBackgroundEpicardial adipose tissue (EAT) regulates coronary artery function via lipid metabolism and immune cell recruitment. Increased EAT is a risk factor for coronary artery disease (CAD), but aerobic exercise mitigates CAD. The effect of aerobic exercise on immune cells in EAT is unknown. We hypothesized that aerobic exercise creates an anti-inflammatory environment characterized by increased M2 macrophages and up-regulation of anti-inflammatory cytokine transcripts in EAT.MethodsFemale Yucatan pigs (n=7) were allocated to sedentary or exercised groups. To mimic CAD, a coronary artery was chronically occluded or remained non-occluded. EAT samples were processed for bulk and single nuclei transcriptomic sequencing.ResultsSub-clustering identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs being dominant. Non-occluded sedentary EAT had the largest percentage of M1 macrophages and CD8+ T cells. Irrespective of occlusion, sedentary EAT had the largest fraction of cells expressing genes in the tumor necrosis factor (TNF) superfamily. Irrespective of occlusion, exercise upregulated peroxisome proliferator-activated receptor (PPAR) gamma (G) expression and enriched PPAR signaling pathways in adipocytes, macrophages, and T cells. However,PPARGexpression was lowest in CD8+ T cells from non-occluded exercised EAT. The greatest number of significant cell-cell communications between adipocytes and immune cells via growth factors and adhesion molecules occurred in occluded sedentary EAT.ConclusionAerobic exercise mitigates the proinflammatory nature of EAT in CAD via modulation of immune cell subpopulations, decreased TNF superfamily and increasedPPARGgene expression, and decreased growth factor communication between adipocytes and immune cells.
Fmr1KO causes delayed rebound spike timing in mediodorsal thalamocortical neurons through regulation of HCN channel activity
Authors: Ordemann Gregory J. , Lyuboslavsky Polina , Kizimenko Alena , Brumback Audrey C. 
Published: February 2025

AbstractBackgroundThe neurodevelopmental disorder Fragile X syndrome (FXS) results from hypermethylation of theFMR1gene which prevents FMRP production. FMRP modulates the expression and function of a wide variety of proteins, including voltage-gated ion channels such as Hyperpolarization-Activated Cyclic Nucleotide gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders. MD connectivity with mPFC is integral to executive functions like working memory and social behaviors that are disrupted in FXS.MethodsWe used a combination of retrograde labeling andex vivobrain slice whole cell electrophysiology in 40 wild type and 42Fmr1KO male mice to investigate how a lack ofFmr1affects intrinsic cellular properties in lateral (MD-L) and medial (MD-M) MD neurons that project to the medial prefrontal cortex (MD→mPFC neurons).ResultsIn MD-L neurons,Fmr1knockout caused a decrease in HCN-mediated membrane properties such as voltage sag and membrane afterhyperpolarization. These changes in subthreshold properties were accompanied by changes in suprathreshold neuron properties such as the variability of action potential burst timing.ConclusionsInFmr1knockout mice, reduced HCN channel activity in MD→mPFC neurons impairs both the timing and magnitude of HCN-mediated membrane potential regulation. Changes in response timing may adversely affect rhythm propagation inFmr1KO thalamocortical circuitry. MD thalamic neurons are critical for maintaining rhythmic activity involved in cognitive and affective functions. Understanding specific mechanisms of thalamocortical circuit activity may lead to therapeutic interventions for individuals with FXS.
Characterisation of facial expressions and behaviours of horses in response to positive and negative emotional anticipation using network analysis
Authors: Phelipon Romane , Bertrand Léa , Jardat Plotine , Reigner Fabrice , Lewis Kate , Micheletta Jérôme , Lansade Léa 
Published: February 2025

AbstractThe welfare of an animal is closely linked to their emotional experiences, making it essential to identify reliable indicators of these emotions. This study aimed to identify behaviours and facial movements in horses experiencing contrasting emotional valence, triggered by the anticipation of a positive condition (going to pasture) or a negative condition (going alone to a novel environment). Twenty horses were daily trained to wait in a starting box before being exposed to these two conditions. After one week of positive training or negative training, we analysed horses’ behaviours, cortisol variations, and facial movements while they waited in their starting box. First, we confirmed that the two conditions induced contrasting emotional valence, as evidenced by the shorter time taken to approach in the positive condition compared to the negative, and by the higher maximal heart rate and cortisol variation in the negative condition. Then using the Equine Facial Action Coding System (EquiFACS) and network analysis (NetFACS) we revealed distinct behaviours and facial expression profiles. In positive anticipation, the horses exhibited a greater range of behaviours, including shaking their heads from side to side, stepping back, sniffing, and pawing at the ground. Additionally, two distinct facial expression profiles were identified as specific to positive and negative anticipation. In positive anticipation, the horses displayed a higher neck, accompanied by a greater frequency of half-blinks and mouth movements. Conversely, in negative anticipation, the horses exhibited a medium neck, with ears backward accompanied by more flattened ears and expressed more nostril movements. The findings highlight the importance of these indicators in characterising horses’ emotions and emphasise their significance for assessing equine welfare.
Protein-Like Polymer for Inhibition of Tau Fibril Propagation in Human-Derived Models of Neurodegeneration
Authors: Longhini Andrew P. , Fattah Mara , Sala-Jarque Julia , DuBose Austin , Rivera Erica Keane , Sclafani Olivia R , Zhou Jessica , Anatot Jacqueline E. , Thompson Matthew P. , Unger Matthew T. , Beckett Emily R. , Fagan Colby , Nakamura Dylan , Morimoto Richard I. , Han Songi , Qiao Baofu , Gianneschi Nathan C. , Kosik Kenneth S. 
Published: February 2025

AbstractThe misfolding, aggregation, and spread of tau protein fibrils underlie tauopathies, a diverse class of neurodegenerative diseases for which effective treatments remain elusive. Among these are corticobasal dementia (CBD) and progressive supranuclear palsy (PSP), canonical examples of 4-repeat (4R) tauopathies characterized by tau isoforms exclusively with four microtubule-binding repeat domains. We target this 4R tau isoform-specific mechanism by focusing on misfolded tau’s distinctive stem-loop-stem structural motif formed by the junction of the 4R-defining alternatively spliced exon and the adjacent constitutive exon. A synthetic peptide based on this stem-loop-stem sequence can induce aggregation and spread in an isoform-specific manner. Here, we develop a protein-like polymer (PLP) in which multiple copies of this synthetic peptide form a brush-like structure capable of preventing tau aggregation by binding and capping fibril endsin vitro, in human brain organoids, and in cellular models with an EC50 of 105 ± 14 nM. PLPs demonstrate robust activity against fibrils derived from CBD and PSP patient brains and a PS19 mouse tauopathy model. Previous tau-targeted treatments have primarily focused on broad tau clearance, aggregation inhibition, or microtubule stabilization, often lacking isoform specificity and precision. In contrast, this approach targets the 4R tau isoform’s unique structural motif, offering a tailored therapeutic intervention for diseases like CBD and PSP. Supported by prior studies showing blood-brain barrier penetrance and safety profiles, this tau-binding PLP offers a promising translational path toward clinical applications in tauopathy treatment.
Atom-wise formulation of the many-body dispersion problem for linear-scaling van der Waals corrections
Authors: Muhli Heikki , Ala-Nissila Tapio , Caro Miguel A. 
Published: February 2025

A common approach to modeling dispersion interactions and overcoming the inaccurate description of long-range correlation effects in electronic structure calculations is the use of pairwise-additive potentials, as in the Tkatchenko-Scheffler [] method. In previous work [H. Muhli , ], we have shown how these are amenable to highly efficient atomistic simulation by machine learning their local parametrization. However, the atomic polarizability and the electron correlation energy have a complex and nonlocal many-body character and some of the dispersion effects in complex systems are not sufficiently described by these types of pairwise-additive potentials. Currently, one of the most widely used rigorous descriptions of the many-body effects is based on the many-body dispersion (MBD) model [A. Tkatchenko , ]. In this work, we show that the MBD model can also be locally parametrized to derive a local approximation for the highly nonlocal many-body effects. With this local parametrization, we develop an atomwise formulation of MBD that we refer to as linear MBD (lMBD), as this decomposition enables linear scaling with system size. This model provides a transparent and controllable approximation to the full MBD model with tunable convergence parameters for a fraction of the computational cost observed in electronic structure calculations with popular density-functional theory codes. We show that our model scales linearly with the number of atoms in the system and is easily parallelizable. Furthermore, we show how using the same machinery already established in previous work for predicting Hirshfeld volumes with machine learning enables access to large-scale simulations with MBD-level corrections.

Published by the American Physical Society
2025
Dynamical metastability and re-entrant localization of trapped active elements with speed and orientation fluctuations
Authors: Patel Manish , Shee Amir , Chaudhuri Debasish 
Published: February 2025

We explore the dynamics of active elements performing persistent random motion with fluctuating active speed and in the presence of translational noise in a d-dimensional harmonic trap, modeling active speed generation through an Ornstein-Uhlenbeck process. Our approach employs an exact analytic method based on the Fokker-Planck equation to compute time-dependent moments of any dynamical variable of interest across arbitrary dimensions. We analyze dynamical crossovers in particle displacement before reaching the steady state, focusing on three key timescales: speed relaxation, persistence, and dynamical relaxation in the trap. Notably, for slow active speed relaxation, we observe an intermediate-time metastable saturation in the mean-squared displacement before reaching the final steady state. The steady-state distributions of particle positions exhibit two types of non-Gaussian departures based on control parameters: bimodal distributions with negative excess kurtosis and heavy-tailed unimodal distributions with positive excess kurtosis. We obtain detailed steady-state phase diagrams using the exact calculation of excess kurtosis, identifying Gaussian and non-Gaussian regions and potential re-entrant transitions.

Published by the American Physical Society
2025
Anxiety, depression and neurocognitive disorder among HIV-infected people in penitentiary institutions of Azerbaijan
Authors: Abdullayeva Nargiz , Mammadbayli Aytan , Taghiyeva Madina 
Published: February 2025

Purpose
This study aims to assess neurocognitive impairment, depression and anxiety level in HIV-infected individuals in penitentiary institutions of Azerbaijan.

Design/methodology/approach
A cross-sectional design was used to recruit incarcerated individuals in penitentiary institutions of Azerbaijan meeting the inclusion criteria (diagnosed with HIV). Participants completed standardized assessments to screen anxiety and depression symptoms, hospital anxiety and depression scale and neurocognitive functioning and mini mental status examination. Demographic and clinical data, including age, gender, HIV disease progression, antiretroviral therapy adherence, history of substance abuse and duration of incarceration, were also collected as covariates of interest. The study was approved by Azerbaijan Medical University Ethics Committee (P.23 / 19.05.2022). Data were analyzed using student-Bonferroni and H−Kruskal−Wallis tests. Variance analysis was conducted using the ANOVA test, while discriminant analyses involved the χ2-Pearson test, through SPSS software, version 26.

Findings
Of the 88 HIV positive patients who agreed to participate, 99% were male, with a median age of 44 years (range: 30–62), median CD4 count 453.1 cells/µl (range: 153–1,290). The prevalence of HIV-associated neurocognitive disorder was 72.7%. Occurrence of comorbid depression and anxiety symptoms was found to be 72% and 67%, respectively. Most patients (59.1%) were HIV-positive for more than five years. Increased depression and anxiety levels were identified mostly in first two years after admission to prison (p < 0.05). HIV-associated neurocognitive disorder was most commonly found among depressed patients (p = 0.009).

Originality/value
The findings of this study provide valuable insights into the cooccurrence and interrelationships between anxiety, depression and neurocognitive disorders in individuals with HIV in prisons. It highlights the unique intersection of HIV infection, mental health challenges and incarceration in a country where research on HIV-related issues in prisons is still developing. Ultimately, this study seeks to contribute to identify targeted interventions that address the mental health needs of incarcerated individuals living with HIV in Azerbaijan, promoting their overall well-being and quality of life.
A fatigue life prediction framework of laser-directed energy deposition Ti-6Al-4V based on physics-informed neural network
Authors: Dang Linwei , He Xiaofan , Tang Dingcheng , Xin Hao , Wu Bin 
Published: February 2025

PurposePores are the primary cause of fatigue failure in laser-directed energy deposition (L-DED) titanium alloys, which are largely determined by their location, size and shape. It is crucial for promoting the application of L-DED titanium alloys and ensuring their safety that establishing a fatigue life prediction method induced by pores, resulting in a proposed fatigue life prediction framework for L-DED Ti-6Al-4V based on a physics-informed neural network (PINN) algorithm.Design/methodology/approachIn this study, a novel fatigue life prediction framework for L-DED Ti-6Al-4V based on a PINN algorithm was proposed. The influence patterns of various fatigue-sensitive parameters were revealed. The paper also included validation and analysis of the method, such as hyperparameter analysis of the PINN, efficacy analysis driven by physical information and comparative analysis of different methods.FindingsThe proposed method demonstrated high accuracy, with a correlation coefficient of 0.99 with experimental life. The coefficient of determination was 0.95 and the mean squared error was 0.06.Originality/valueThe results indicate that the proposed fatigue life prediction framework was of strong generalization capability and robustness.
Opting for smart hotels: do digital immigrants perceive differently than digital natives do?
Authors: Yan Zhuoma , Konar Rupam , Sthapit Erose , Balasubramanian Kandappan , Chen Lei , Prentice Catherine 
Published: February 2025

PurposeThis study expanded the model of technology acceptance and investigated how the relationship between usefulness, ease of use, efficiency, personalization, safety and security and behavioural intention differ on Gen Z and silver tourists toward smart hotel. This study further applies multiple group analysis to examine whether there are substantial differences among these two groups of respondents.Design/methodology/approachUsing an online survey, this study was undertaken with Gen Z and silver tourists in mainland China who had stayed in smart hotel over the past 12 months. A total of 474 valid responses were collected. Structural equation modelling and multigroup analysis were employed to test the proposed relationships.FindingsThis study revealed that personalization did not affect the behavioural intention among Gen Z tourists, meanwhile, there is no positive relationship between usefulness, efficiency and behavioural intention on silver group. Additionally, the findings revealed that there are no substantial differences among Gen Z (digital natives) and silver customers (digital immigrants) regarding smart hotel behavioural intentions.Practical implicationsThis study offers strategic guidance for hotel managers to design and reposition smart hotel based on different customer sectors. Further, important implications for smart devices manufacturers are also provided to improve the functioning of hotel service robots.Originality/valueThis is the first study to compare the drivers and outcomes of behavioural intentions among different age groups of tourists toward smart hotels.
Sustainable management in the hospitality industry: the influence of green human resource management on employees’ pro-environmental behavior and environmental performance
Authors: Vu Tuan Duong , Nguyen Thi Thanh Nhan , Nguyen Hoang Nam , Nguyen Manh Hung 
Published: February 2025

PurposeThis study aims to evaluate the impact of green human resource management on cognitive factors, employees' pro-environmental behavior and the environmental performance of hotels in Vietnam.Design/methodology/approachDrawing upon primary data collected from a sample of 393 hotel employees, this study utilizes covariance-based structural equation modeling (CB-SEM) to test hypotheses and conduct path analysis.FindingsThe study’s findings reveal several key insights. Firstly, GHRM positively influences environmental knowledge (EK), environmental attitude (EA), attitude toward pro-environmental behavior (APB), pro-environmental behavior (PB) of employees and environmental performance (EP) of hotels. Additionally, the results also indicate that EK promotes EA, APB and PB, and both EA and EK can predict PB of employees. Surprisingly, the results from CB-SEM analysis reject the direct impact of APB on PB. Moreover, this study also confirmed the positive influence of PB on EP of hotels. Notably, the research delves into the moderating effect of work overload (WO) on the associations between GHRM and PB, as well as APB and PB.Practical implicationsThe findings offer valuable recommendations for hotel managers and policymakers, aiming for effective GHRM practices and improvement of employees’ PB and EP of hotels.Originality/valueThis study broadens the understanding of sustainable management practices, specifically in human resource management in the hospitality industry. Notably, it identifies significant avenues to address theoretical gaps left by previous studies.