bluuebunny/crossref_metadata_2025_split huggingface dataset:
IsRNAcirc: 3D structure prediction of circular RNAs based on coarse-grained molecular dynamics simulation
Authors: Jiang Haolin , Xu Yulian , Tong Yunguang , Zhang Dong , Zhou Ruhong 
Published: July 2024

AbstractAs an emerging class of RNA molecules, circular RNAs play pivotal roles in various biological processes, thereby determining their three-dimensional (3D) structure is crucial for a deep understanding of their biological significances. Similar to linear RNAs, the development of computational methods for circular RNA 3D structure prediction is challenging, especially considering the inherent flexibility and potentially long length of circular RNAs. Here, we introduce an extension of our previous IsRNA2 model, named IsRNAcirc, to enable circular RNA 3D structure predictions through coarse-grained molecular dynamics simulations. The workflow of IsRNAcirc consists of four main steps, including input preparation, end closure, structure prediction, and model refinement. Our results demonstrate that IsRNAcirc can provide reasonable 3D structure predictions for circular RNAs, which significantly reduce the locally irrational elements contained in the initial input. Moreover, for a validation test set comprising 34 circular RNAs, our IsRNAcirc can generate 3D models with better scores than the template-based 3dRNA method. These findings demonstrate that our IsRNAcirc method is a promising tool to explore the structural details along with intricate interactions of circular RNAs.Author SummaryKnowledge of the 3D structure of circular RNA molecules can help us better understand their roles in eukaryotic cells. However, experimental determination of circular RNA 3D structure remains challenging, with currently only one complete circular RNA 3D structure available in the Protein Data Bank. Thus, extending from their linear counterparts, computational methods that can predict circular RNA 3D structure are urgently needed. In particular, physics-basedde novo3D structure prediction methods are promising due to their powerful sampling capability in the conformational space, which avoid the problem of limited available templates in template-based approaches. We have developed IsRNAcirc, a new physics-based method that employs an accurate coarse-grained force field and replica-exchange molecular dynamics simulations to predict the 3D structure of circular RNAs. IsRNAcirc is shown to significantly reduce the number of locally irrational structures in the input trials, which are caused by the lack of suitable templates and the improper assembly of fragments. Furthermore, in the absence of experimental reference structures, the predicted 3D models were validated using the popular scoring functions, such as DFIRE-RNA and rsRNASP, demonstrating that IsRNAcirc outperforms the template-based 3dRNA method in generating low-energy conformations.
Multi-scale modelling of location- and frequency-dependent synaptic plasticity induced by transcranial magnetic stimulation in the dendrites of pyramidal neurons
Authors: Hananeia Nicholas , Ebner Christian , Galanis Christos , Cuntz Hermann , Opitz Alexander , Vlachos Andreas , Jedlicka Peter 
Published: July 2024

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) induces long-term changes of synapses, but the mechanisms behind these modifications are not fully understood. Al- though there has been progress in the development of multi-scale modeling tools, no com- prehensive module for simulating rTMS-induced synaptic plasticity in biophysically realistic neurons exists..ObjectiveWe developed a modelling framework that allows the replication and detailed prediction of long-term changes of excitatory synapses in neurons stimulated by rTMS.MethodsWe implemented a voltage-dependent plasticity model that has been previously established for simulating frequency-, time-, and compartment-dependent spatio-temporal changes of excitatory synapses in neuronal dendrites. The plasticity model can be incorporated into biophysical neuronal models and coupled to electrical field simulations.ResultsWe show that the plasticity modelling framework replicates long-term potentiation (LTP)-like plasticity in hippocampal CA1 pyramidal cells evoked by 10-Hz repetitive magnetic stimulation (rMS). This plasticity was strongly distance dependent and concentrated at the proximal synapses of the neuron. We predicted a decrease in the plasticity amplitude for 5 Hz and 1 Hz protocols with decreasing frequency. Finally, we successfully modelled plasticity in distal synapses upon local electrical theta-burst stimulation (TBS) and predicted proximal and distal plasticity for rMS TBS. Notably, the rMS TBS-evoked synaptic plasticity exhibited robust facilitation by dendritic spikes and low sensitivity to inhibitory suppression.ConclusionThe plasticity modelling framework enables precise simulations of LTP-like cellular effects with high spatio-temporal resolution, enhancing the efficiency of parameter screening and the development of plasticity-inducing rTMS protocols.HighlightsFirst rigorously validated model of TMS-induced long-term synaptic plasticity in ex- tended neuronal dendrites that goes beyond point-neuron and mean-field modellingRobust simulations of experimental data on LTP-like plasticity in the proximal dendrites of CA1 hippocampal pyramidal cells evoked by 10 Hz repetitive magnetic stimulation (rMS)Replication of distal synaptic plasticity for a local electrical theta burst stimulation (TBS) protocolPrediction of distal and proximal LTP-like plasticity for rMS TBS1 Hz rMS does not induce long-term depression
A Safe and Effective New Method for Thin Cornea Cross-linking
Authors: Zhou Shengmei , Lin Zhirong , Hong Yi , Liao Yi 
Published: July 2024

AbstractThe mechanical properties of the collagen matrix determine the corneal regularity. Thus, corneal thinning, cone-like protrusion, and loss of corneal astigmatism characterize corneal ecstatic diseases, including keratoconus and post-LASIK ectasia. Currently, riboflavin (RF)/ultraviolet A (UVA) based corneal collagen cross-linking (CXL) is commonly used in clinics to stiffen cornea and halt disease progression in patients. However, due to tissue damage, especially irreversible endothelium loss, standard RF/UVA protocol is only allowed in eyes with corneal thickness over 400 μm after epithelium debridement. Thus, lots of patients with thin cornea have limited therapeutic options. Here, we introduced a new strategy to cross-link cornea collagens using synthesized photo-initiators lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and visible blue light (BL). The LAP/BL protocol could effectively increase corneal stiffness, similar to the RF/UVA protocol in both porcine and rabbit cornea. When the LAP/BL protocol was used, both epithelial wound healing, stromal cell repopulation, and corneal edema recovery rates were accelerated compared with the RF/UVA protocol. More importantly, as BL is used instead of UVA, corneal endothelium was mostly preserved in both rabbit and mouse models even when cornea thickness was as thin as 100 μm. In summary, we propose that the LAP/BL protocol is a safe and effective choice for thin cornea CXL.
An orbitocortical-thalamic circuit suppresses binge alcohol-drinking
Authors: Gimenez-Gomez P , Le T , Zinter M , M’Angale P , Duran-Laforet V , Freels TG , Pavchinskiy R , Molas S , Schafer DP , Tapper AR , Thomson T , Martin GE 
Published: July 2024

SummaryAlcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.
Torque Teno Sus Virus 1: A Potential Surrogate Pathogen to Study Pig-Transmitted Transboundary Animal Diseases
Authors: Li Xiaolong , Parker Brandon M. , Boughton Raoul K. , Beasley James C. , Smyser Timothy J. , Austin James D. , Pepin Kim M. , Miller Ryan S. , Vercauteren Kurt C. , Wisely Samantha M. 
Published: July 2024

AbstractUnderstanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given challenges associated with studying TADs in free-ranging populations, a surrogate pathogen system forin situstudies of pathogen dynamics would be ideal to elucidate how pathogens may circulate and be maintained within populations, how they may spillover into domestic populations, and how disease spread may be mitigated. We assessed the suitability of Torque teno sus virus 1 (TTSuV1) to serve as a surrogate pathogen for molecular epidemiological studies in wild pigs by investigating the prevalence, persistence, correlation with host health status and genetic variability at two study areas: Archbold’s Buck Island Ranch in Florida and Savannah River Site in South Carolina. We then conducted a molecular epidemiological case study within the Archbold’s Buck Island Ranch site to determine how analysis of this pathogen could inform transmission studies. Prevalence was high at both study areas (40%,n= 190). Phylogenetic analyses revealed high levels of genetic variability within and between study sites. Our case study showed that pairwise host relatedness and geographic distance were highly correlated to pairwise viral genetic similarity. Molecular epidemiological analyses revealed a distinct pattern of direct transmission from pig to pig occurring within and between family groups. Our results suggest TTSuV1 is highly suitable for molecular epidemiological analyses and will be useful for futurein situstudies of transmission dynamics in wild pigs.
Agent-Based Modeling of Virtual Tumors Reveals the Critical Influence of Microenvironmental Complexity on Immunotherapy Efficacy
Authors: Wang Yixuan , Bergman Daniel R. , Trujillo Erica , Fernald Anthony A. , Li Lie , Pearson Alexander T. , Sweis Randy F. , Jackson Trachette L. 
Published: July 2024

AbstractSince the introduction of the first immune checkpoint inhibitor (ICI), immunotherapy has changed the landscape of molecular therapeutics for cancers. However, ICIs do not work equally well on all cancers and for all patients. There has been a growing interest in using mathematical and computational models to optimize clinical responses. Ordinary differential equations (ODEs) have been widely used for mechanistic modeling in immuno-oncology and immunotherapy because they allow rapid simulations of temporal changes in the cellular and molecular populations involved. Nonetheless, ODEs cannot describe the spatial structure in the tumor microenvironment or quantify the influence of spatially-dependent characteristics of tumor-immune dynamics. For these reasons, agent-based models (ABMs) have gained popularity because they can model more detailed phenotypic and spatial heterogeneity that better reflect the complexity seen in vivo. In the context of anti-PD-1 ICIs, we compare treatment outcomes simulated from an ODE model and an ABM to show the importance of including spatial components in computational models of cancer immunotherapy. We consider tumor cells of high and low antigenicity and two distinct cytotoxic T lymphocyte (CTL) killing mechanisms. The preferred mechanism differs based on the antigenicity of tumor cells. Our ABM reveals varied phenotypic shifts within the tumor and spatial organization of tumor and CTLs, despite similarities in key immune parameters, initial conditions of simulation, and early temporal trajectories of the cell populations.
A scene with an invisible wall - navigational experience shapes visual scene representation
Authors: Li Shi Pui Donald , Shao Jiayu , Lu Zhengang , McCloskey Michael , Park Soojin 
Published: July 2024

ABSTRACTHuman navigation heavily relies on visual information. Although many previous studies have investigated how navigational information is inferred from visual features of scenes, little is understood about the impact of navigational experience on visual scene representation. In this study, we examined how navigational experience influences both the behavioral and neural responses to a visual scene. During training, participants navigated in the virtual reality (VR) environments which we manipulated navigational experience while holding the visual properties of scenes constant. Half of the environments allowed free navigation (navigable), while the other half featured an ‘invisible wall’ preventing the participants to continue forward even though the scene was visually navigable (non-navigable). During testing, participants viewed scene images from the VR environment while completing either a behavioral perceptual identification task (Experiment1) or an fMRI scan (Experiment2). Behaviorally, we found that participants judged a scene pair to be significantly more visually different if their prior navigational experience varied, even after accounting for visual similarities between the scene pairs. Neurally, multi-voxel pattern of the parahippocampal place area (PPA) distinguished visual scenes based on prior navigational experience alone. These results suggest that the human visual scene cortex represents information about navigability obtained through prior experience, beyond those computable from the visual properties of the scene. Taken together, these results suggest that scene representation is modulated by prior navigational experience to help us construct a functionally meaningful visual environment.
Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy
Authors: Biswas Leelabati , Tyc Katarzyna M. , Aboelenain Mansour , Sun Siqi , Dundović Iva , Vukušić Kruno , Liu Jason , Guo Vanessa , Xu Min , Scott Richard T. , Tao Xin , Tolić Iva M. , Xing Jinchuan , Schindler Karen 
Published: July 2024

AbstractThe female reproductive lifespan depends on egg quality, particularly euploidy. Mistakes in meiosis leading to egg aneuploidy are common, but the genetic landscape causing this is not well understood due to limited phenotypic data. We identify genetic determinants of reproductive aging via egg aneuploidy using a biobank of maternal exomes linked with maternal age and embryonic aneuploidy data. We found 404 genes with variants enriched in individuals with high egg aneuploidy rates and implicate kinesin protein family genes in aneuploidy risk. Experimental perturbations showed that motor domain variants in these genes increase aneuploidy in mouse oocytes. A knock-in mouse model validated that a specific variant in kinesinKIF18Aaccelerates reproductive aging and diminishes fertility. These findings suggest potential non-invasive biomarkers for egg quality, aiding personalized fertility medicine.One sentence summaryThe study identifies novel genetic determinants of reproductive aging linked to egg aneuploidy by analyzing maternal exomes and demonstrates that variants in kinesin genes, specificallyKIF18A, contribute to increased aneuploidy and accelerated reproductive aging, offering potential for personalized fertility medicine.
Radiomic-Based Approaches in the Multi-metastatic Setting: A Quantitative Review
Authors: Geady Caryn , Patel Hemangini , Peoples Jacob , Simpson Amber , Haibe-Kains Benjamin 
Published: July 2024

AbstractBackgroundRadiomics traditionally focuses on analyzing a single lesion within a patient to extract tumor characteristics, yet this process may overlook inter-lesion heterogeneity, particularly in the multi-metastatic setting. There is currently no established method for combining radiomic features in such settings, leading to diverse approaches with varying strengths and limitations. Our quantitative review aims to illuminate these methodologies, assess their replicability, and guide future research toward establishing best practices, offering insights into the challenges of multi-lesion radiomic analysis across diverse datasets.MethodsWe conducted a comprehensive literature search to identify methods for integrating data from multiple lesions in radiomic analyses. We replicated these methods using either the author’s code or by reconstructing them based on the information provided in the papers. Subsequently, we applied these identified methods to three distinct datasets, each depicting a different metastatic scenario.ResultsWe compared ten mathematical methods for combining radiomic features across three distinct datasets, encompassing a total of 16,850 lesions in 3,930 patients. Performance of these methods was evaluated using the Cox proportional hazards model and benchmarked against univariable analysis of total tumor volume. We observed variable performance in methods across datasets. However, no single method consistently outperformed others across all datasets. Notably, while some methods surpassed total tumor volume analysis in certain datasets, others did not. Averaging methods showed higher median performance in patients with colorectal liver metastases, and in soft tissue sarcoma, concatenation of radiomic features from different lesions exhibited the highest median performance among tested methods.ConclusionsRadiomic features can be effectively selected or combined to estimate patient-level outcomes in multi-metastatic patients, though the approach varies by metastatic setting. Our study fills a critical gap in radiomics research by examining the challenges of radiomic-based analysis in this setting. Through a comprehensive review and rigorous testing of different methods across diverse datasets representing unique metastatic scenarios, we provide valuable insights into effective radiomic analysis strategies.
Regeneration recapitulates many embryonic processes, including reuse of developmental regulatory regions
Authors: Loubet-Senear Kaitlyn , Srivastava Mansi 
Published: July 2024

ABSTRACTThe wide distribution of regenerative capacity across the animal tree of life raises the question of how regeneration has evolved in distantly-related animals. Given that whole-body regeneration shares the same end-point – formation of a functional body plan – as embryonic development, it has been proposed that regeneration likely recapitulates developmental processes to some extent. Therefore, understanding how developmental processes are reactivated during regeneration is important for uncovering the evolutionary history of regeneration. Comparative transcriptomic studies in some species have revealed shared gene expression between development and regeneration, but it is not known whether these shared expression profiles correspond to shared functions, and which mechanisms activate expression of developmental genes during regeneration. We sought to address these questions using the acoelHofstenia miamia, which is amenable to studies of both embryonic development and whole-body regeneration. By examining functionally validated regeneration processes during development at single-cell resolution, we found that whereas patterning and cellular differentiation are largely similar, wound response programs have distinct dynamics between development and regeneration. Chromatin accessibility analyses revealed that regardless of playing concordant or divergent roles during regeneration and development, genes expressed in both processes are frequently controlled by the same regulatory regions, potentially via utilization of distinct transcription factor binding sites. This study extends the known correspondence of development and regeneration from broad transcriptomic similarity to include patterning and differentiation processes. Further, our work provides a catalog of regulatory regions and binding sites that potentially regulate developmental genes during regeneration, fueling comparative studies of regeneration.
Oxygen metabolism in descendants of the archaeal-eukaryotic ancestor
Authors: Appler Kathryn E. , Lingford James P. , Gong Xianzhe , Panagiotou Kassiani , Leão Pedro , Langwig Marguerite , Greening Chris , Ettema Thijs J. G. , De Anda Valerie , Baker Brett J. 
Published: July 2024

AbstractAsgard archaea were pivotal in the origin of complex cellular life. Hodarchaeales (Asgardarchaeota class Heimdallarchaeia) were recently shown to be the closest relatives of eukaryotes. However, limited sampling of these archaea constrains our understanding of their ecology and evolution1–3, including their anticipated role in eukaryogenesis. Here, we nearly double the number of Asgardarchaeota metagenome-assembled genomes (MAGs) to 869, including 136 new Heimdallarchaeia (49 Hodarchaeales) and several novel lineages. Examining global distribution revealed Hodarcheales are primarily found in coastal marine sediments. Detailed analysis of their metabolic capabilities revealed guilds of Heimdallarchaeia are distinct from other Asgardarchaeota. These archaea encode hallmarks of aerobic eukaryotes, including electron transport chain complexes (III and IV), biosynthesis of heme, and response to reactive oxygen species (ROS). The predicted structural architecture of Heimdallarchaeia membrane-bound hydrogenases includes additional Complex-I-like subunits potentially increasing the proton motive force and ATP synthesis. Heimdallarchaeia genomes encode CoxD, which regulates the electron transport chain (ETC) in eukaryotes. Thus, key hallmarks for aerobic respiration may have been present in the Asgard-eukaryotic ancestor. Moreover, we found that Heimdallarchaeia is present in a variety of oxic marine environments. This expanded diversity reveals these Archaea likely conferred energetic advantages during early stages of eukaryogenesis, fueling cellular complexity.