bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of three novel neutralizing antibody epitopes on the human astrovirus capsid spike and mechanistic insights into virus neutralization
Authors: Lanning Sarah , Aguilar-Hernández Nayeli , Serrão Vitor Hugo B , López Tomás , O’Rourke Sara M. , Lentz Adam , Ricemeyer Lena , Espinosa Rafaela , López Susana , Arias Carlos F. , DuBois Rebecca M.
Published: September 2024

Human astroviruses (HAstVs) are a leading cause of viral childhood diarrhea that infect nearly every individual during their lifetime. Although human astroviruses are highly prevalent, no approved vaccine currently exists. Antibody responses appear to play an important role in protection from HAstV infection, however knowledge about the neutralizing epitope landscape is lacking, as only 3 neutralizing antibody epitopes have previously been determined. Here, we structurally define the epitopes of 3 uncharacterized HAstV-neutralizing monoclonal antibodies: antibody 4B6 with X-ray crystallography to 2.67 Å, and antibodies 3H4 and 3B4 simultaneously with single-particle cryogenic-electron microscopy to 3.33 Å. We assess the epitope locations relative to conserved regions on the capsid spike and find that while antibodies 4B6 and 3B4 target the upper variable loop regions of the HAstV spike protein, antibody 3H4 targets a novel region near the base of the spike that is more conserved. Additionally, we found that all 3 antibodies bind with high affinity, and they compete with receptor FcRn binding to the capsid spike. These studies inform which regions of the HAstV capsid can be targeted by monoclonal antibody therapies and could aid in rational vaccine design.

Importance

Human astroviruses infect nearly every child in the world, causing diarrhea, vomiting, and fever. Despite the prevalence of human astroviruses, little is known about how antibodies block virus infection. Here, we determined high-resolution structures of the astrovirus capsid protein in complex with three virus-neutralizing antibodies. The antibodies bind distinct sites on the capsid spike domain. We find that the antibodies block virus attachment to human cells and prevent capsid spike interaction with the human neonatal Fc receptor. These findings support the use of the human astrovirus capsid spike as an antigen in a vaccine to prevent astrovirus disease.
Phase-Dependent Stimulation of the Hippocampus: A Computational Modeling Approach
Authors: Lee Hsin-Pei , Arginteanu Toren , Kudela Pawel , Anderson William S. , Salimpour Yousef
Published: September 2024

Phase-amplitude coupling (PAC) between brain oscillations of different frequencies plays a fundamental role in neural processing, and phase-dependent neuromodulation has emerged as a promising strategy to modulate PAC. In the hippocampus, theta-gamma PAC is critically involved in memory-related functions and information propagation. Computational models provide a valuable platform for investigating the neurobiological mechanisms underlying phase- dependent effects, bypassing the limitations of in vivo and in vitro experiments. In this study, we extended a previously published computational model of the hippocampal CA3 region using the NEURON and Python environments. A closed-loop autoregressive (AR) forward prediction model was employed to sample the network’s local field potential (LFP) in real time, enabling the precise calculation of phase-locked stimulus time points. Our results demonstrated the successful delivery of phase-locked current injections to all neuronal populations at both the peak and trough of theta oscillations. Phase-specific alterations in the theta band were observed during stimulation, along with enhanced theta-gamma coupling induced by peak-phase stimulation. Single neuron activity analysis highlighted the critical role of oriens lacunosum- moleculare (OLM) cells in modulating phase-dependent network dynamics. These findings underscore the potential of closed-loop stimulation systems to modulate PAC, with significant implications for the treatment of neurological disorders characterized by abnormal oscillatory activity, such as Alzheimer’s disease and other memory-related disorders.

Significance Statement

By employing a computational model of the hippocampal CA3 region, we reveal the ability of the phase-dependent stimulation technique to modulate phase-amplitude coupling, a critical mechanism in memory and information processing. Our findings highlight the importance of precise phase-locked stimulation and the key role of specific interneurons in regulating network dynamics. These insights lay the groundwork for developing targeted neuromodulation therapies to restore normal oscillatory patterns in the brain, with promising implications for treating memory-related neurological disorders.
Combined transcriptomic, connectivity, and activity profiling of the medial amygdala using highly amplified multiplexedin situhybridization (hamFISH)
Authors: Edwards Mathew D. , Yin Ziwei , Sueda Risa , Gubanova Alina , Xu Chang S. , Lakner Virág , Murchie Megan , Lee Chi-Yu , Ng Kristal , Farrell Karolina , Faraway Rupert , Ganguly Subham , Jacobs Elina , Bintu Bogdan , Isogai Yoh
Published: September 2024

In situtranscriptomic technologies provide a promising avenue to link gene expression, connectivity, and physiological properties of neural cell types. Commercialized methods that allow the detection of hundreds of genesin situ, however, are expensive and therefore typically used for generating unimodal reference data rather than for resource-intensive multimodal analyses. A major bottleneck is the lack of a routine means to efficiently generate cell type data. Here, we have developed hamFISH (highly amplified multiplexedin situhybridization), which enables the sequential detection of 32 genes using multiplexed branched DNA amplification. We used hamFISH to profile the projection, activity, and transcriptomic diversity of the medial amygdala (MeA), a critical node for innate social and defensive behaviors in mice. In total, we profiled 643,834 cells and classified neurons into 16 inhibitory and 10 excitatory types, many of which were found to be spatially clustered. We then examined the organization of outputs of these cells and activation profiles during different social contexts. Therefore, by facilitating multiplexed detection of single molecule RNAs, hamFISH provides a streamlined and versatile platform for multimodal profiling of specific brain nuclei.
Modeling Sensorimotor Processing with Physics-Informed Neural Networks
Authors: Perez Rotondo Adriana , Marin Vargas Alessandro , Dimitriou Michael , Mathis Alexander
Published: September 2024

Proprioception is essential for planning and executing precise movements. Muscle spindles, the key mechanoreceptors for proprioception, are the principle sensory neurons enabling this process. Emerging evidence suggests spindles act as adaptable processors, modulated by gamma motor neurons to meet task demands. Yet, the specifics of this modulation remain unknown. Here, we present a novel, physics-informed neural network model that integrates biomechanics and neural dynamics to capture spindle function with high fidelity and efficiency, while maintaining computational tractability. Through validation across multiple experimental datasets and species, our model not only outperforms existing approaches but also reveals key drivers of variability in spindle responses, offering new insights into proprioceptive mechanisms.
Exploiting correlations across trials and behavioral sessions to improve neural decoding
Authors: Zhang Yizi , Lyu Hanrui , Hurwitz Cole , Wang Shuqi , Findling Charles , Hubert Felix , Pouget Alexandre ,   International Brain Laboratory, Varol Erdem , Paninski Liam
Published: September 2024

Traditional neural decoders model the relationship between neural activity and behavior within individual trials of a single experimental session, neglecting correlations across trials and sessions. However, animals exhibit similar neural activities when performing the same behavioral task, and their behaviors are influenced by past experiences from previous trials. To exploit these informative correlations in large datasets, we introduce two complementary models: a multi-session reduced-rank model that shares similar behaviorally-relevant statistical structure in neural activity across sessions to improve decoding, and a multi-session state-space model that shares similar behavioral statistical structure across trials and sessions. Applied across 433 sessions spanning 270 brain regions in the International Brain Laboratory public mouse Neuropixels dataset, our decoders demonstrate improved decoding accuracy for four distinct behaviors compared to traditional approaches. Unlike existing deep learning approaches, our models are interpretable and efficient, uncovering latent behavioral dynamics that govern animal decision-making, quantifying single-neuron contributions to decoding behaviors, and identifying different activation timescales of neural activity across the brain. Code:https://github.com/yzhang511/neural_decoding.
Polysaccharide BAP1 ofBifidobacterium adolescentisCCDM 368 attenuates ovalbumin-induced allergy through inhibition of Th2 immunity in mice
Authors: Pacyga-Prus Katarzyna , Hornikova Tereza , Šrůtková Dagmar , Leszczyńska-Nowak Katarzyna , Zabłocka Agnieszka , Schwarzer Martin , Górska Sabina
Published: September 2024

Allergies have become a growing problem and the number of cases is increasing yearly. Administration of postbiotics, well-defined bacterial molecules, is gaining attention as a novel and promising strategy to ameliorate the allergic burden. The BAP1 polysaccharide (PS) ofBifidobacterium adolescentisCCDM 368, was previously characterized by us regarding its structure andin vitroimmunomodulatory properties. Here, to decipher the effect of BAP1 on immune system development, it was intranasally (i.n.) administered to germ-free mice. We observed increased IgA in bronchoalveolar lavage (BAL) fluid, decreased CCL2 production, and higherRorcgene expression in the lung. The intranasal administration of BAP1 reduced lung inflammation and decreased eosinophils numbers in BAL in the ovalbumin-induced allergy mouse model. Moreover, BAP1 decreased OVA-specific IgE levels in sera and Th2-related cytokines in OVA-stimulated splenocytes and lung cells. Finally, increasedRorcand inhibitedIl10gene expression were observed in lung tissue indicating their possible role in BAP1 function. Our findings support and expand on our previousin vitro and ex vivostudies by demonstrating that BAP1, with a unique chemical structure, induces a specific immunomodulatory effect in the host and could be potentially used for alleviating allergic diseases.

Graphical abstract
A hybrid bioprinting-electrospinning platform integrating nanofibers and mesenchymal cell spheroids for customizable wound healing dressings
Authors: Hosseini Seyede Atefe , Planz Viktoria , Stelzer Ernst H. K. , Windbergs Maike , Pampaloni Francesco
Published: September 2024

We introduce a platform for the fabrication of customizable wound healing dressing. The platform integrates electrospun nanofibers, bioprinted hydrogels, and cellular spheroids into hierarchical, fiber-reinforced hybrid constructs. The construct leverages the mechanical strength of polycaprolactone (PCL) nanofibers and the ECM-like properties of GelMA/PEGDA hydrogel. These materials support the incorporation of bone marrow-derived mesenchymal stem cell (BM-hMSC) spheroids, which act as a supportive “cell niche,” enhancing the viability of the hMSC during and after bioprinting, and facilitating their spreading across the construct during the maturation phase. The characterization of the hybrid constructs demonstrated strong structural integrity and enhanced mechanical properties, making them well-suited for clinical wound dressing applications.In vitroassays, including live/dead staining, MTT assays, and scratch assays, revealed increased cell attachment, proliferation, and migration. The spheroids maintained their viability over extended periods, significantly contributing to wound closure in the scratch assay. This innovative approach, which combines electrospinning and light-based bioprinting, offers a promising strategy for the development of customizable wound dressings that closely adapt to the complex architecture of human skin. The bioprinting approach allows for the creation of tailored geometries for specific clinical requirements. Future research will focus on optimizing scaffold design and conducting long-termin vivostudies to validate the platform’s clinical potential.
Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen
Authors: Raghunandanan Sajith , Priya Raj , Lin Gaofeng , Alanazi Fuad , Zoss Andrew , Warren Elise , Yang X. Frank
Published: September 2024

InBorrelia burgdorferi, the Lyme disease pathogen, differential gene expression is primarily controlled by the alternative sigma factor RpoS (σS). Understanding how RpoS levels are regulated is crucial for elucidating howB. burgdorferiis maintained throughout its enzootic cycle. Our recent studies have shown that a homolog of Fur/PerR repressor/activator, BosR, functions as an RNA-binding protein that controls therpoSmRNA stability. However, the mechanisms of regulation of BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we revealed a positive feedback loop between RpoS and BosR, where RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion ofrpoSsignificantly reduced BosR levels, while artificial induction ofrpoSresulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affectbosRmRNA levels but instead modulates the turnover rate of the BosR protein. Furthermore, we demonstrated that environmental cues do not directly influencebosRexpression but instead inducerpoStranscription and RpoS production, thereby enhancing BosR protein levels. This discovery adds a new layer of complexity to the RpoN-RpoS pathway and suggests the need to re-evaluate the factors and signals previously believed to regulate RpoS levels through BosR.

IMPORTANCE

Lyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent,Borreliella(orBorrelia)burgdorferi, is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection ofB. burgdorferi. This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disruptB. burgdorferi’s enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria.
Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening
Authors: Thakur Bhishem , Katte Revansiddha H. , Xu Wang , Janowska Katarzyna , Sammour Salam , Henderson Rory , Lu Maolin , Kwong Peter D. , Acharya Priyamvada
Published: September 2024

The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminal stretch of the envelope (Env) gp41 subunit1–3. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41 and assembles into a trimer, in which FP is accessible for antibody binding3. Env conformational changes or “opening” that follow receptor binding result in FP relocating to a newly formed interprotomer pocket at the gp41-gp120 interface where it is sterically inaccessible to antibody4. The mechanistic steps connecting the entry-related transition of antibody accessible-to-inaccessible FP configurations remain unresolved. Here, using SOSIP-stabilized Env ectodomains5, we visualized atomic-level details of a functional entry intermediate, where partially open Env was bound to receptor CD4, co-receptor mimetic antibody 17b, and FP-targeting antibody VRC34.01, demonstrating that FP remains antibody accessible despite substantial receptor-induced Env opening. We determined a series of structures delineating stepwise opening of Env from its closed state to a newly resolved intermediate and defining downstream re-organizations of the gp120-gp41 interface that ultimately resulted in FP burial in an antibody-inaccessible configuration. Our studies improve our understanding of HIV-1 entry and provide information on entry-related conformation reorganization of a key site of HIV vulnerability to neutralizing antibody.
Megabouts: a flexible pipeline for zebrafish locomotion analysis
Authors: Jouary Adrien , Silva Pedro T.M. , Laborde Alexandre , Mata J. Miguel , Marques João C. , Collins Elena M. D. , Peterson Randall T. , Machens Christian K. , Orger Michael B.
Published: September 2024

Accurate quantification of animal behavior is crucial for advancing neuroscience and for defining reliable physiological markers. We introduce Megabouts (megabouts.ai), a software package standardizing zebrafish larvae locomotion analysis across experimental setups. Its flexibility, achieved with a Transformer neural network, allows the classification of actions regardless of tracking methods or frame rates. We demonstrate Megabouts’ ability to quantify sensorimotor transformations and enhance sensitivity to drug-induced phenotypes through high-throughput, high-resolution behavioral analysis.
Synaptonemal complex protects double-Holliday junctions during meiosis
Authors: Tang Shangming , Koo Jennifer , Pourhosseinzadeh Mohammad , Nguyen Emerald , Liu Natalie , Ma Christopher , Lu Hanyu , Lee Monica , Hunter Neil
Published: September 2024

Chromosomal linkages formed through crossover recombination are essential for accurate segregation of homologous chromosomes during meiosis1. DNA events of recombination are spatially and functionally linked to structural components of meiotic chromosomes2. Imperatively, biased resolution of double-Holliday junction (dHJ) intermediates into crossovers3,4occurs within the synaptonemal complex (SC), the meiosis-specific structure that mediates homolog synapsis during the pachytene stage5,6. However, the SC’s role in crossing over remains unclear. Here we show that SC promotes crossover-specific resolution by protecting dHJs from unscheduled and aberrant resolution. When key SC components are conditionally inactivated during pachytene, dHJs are resolved into noncrossover products by Sgs1-Top3-Rmi1 (STR), the yeast ortholog of the human BLM complex7. Cohesin, the core component of SC lateral elements, plays a primary role in chromatin organization and is required to maintain both SCs and crossover recombination complexes (CRCs) during pachytene. SC central region component Zip1 is required to maintain CRCs even when dHJs are stabilized by inactivating STR. Reciprocally, SC stability requires continuous presence of CRCs, an unanticipated interdependence with important implications for SC dynamics. In conclusion, through hierarchical and interdependent functions of its key components, the SC enables crossover-specific dHJ resolution and thereby ensures the linkage and segregation of homologous chromosomes.
EEG frontal alpha asymmetry mediates the association between maternal and child internalizing symptoms in childhood
Authors: Sacks Dashiell D. , Wang Yiyi , Abron Asja , Mulligan Kaitlin M. , Kelsey Caroline M. , Xie Wanze , Nelson Charles A. , Enlow Michelle Bosquet
Published: September 2024

Background

Anxiety and depression are highly prevalent in youth and can cause significant distress and functional impairment. The presence of maternal anxiety and depression are well-established risk factors for child internalizing psychopathology, yet the responsible mechanisms linking the two remain unclear.

Methods

We examined the potential mediating and moderating roles of EEG frontal alpha asymmetry (FAA) in the intergenerational transmission of internalizing symptoms in a longitudinal sample ofN= 323 mother-child dyads. Self-report maternal internalizing symptoms were evaluated at child age 3 years and 5 years, child EEG at 5 years, and parent-report child internalizing symptoms at age 7 years. Mediation was evaluated via bootstrapped (N= 5000) confidence intervals.

Results

We found significant associations among maternal internalizing (anxiety, depressive) symptoms at child ages 3 and 5 years, child FAA at age 5 years, and child internalizing symptoms at age 7 years. There was a significant mediation effect, whereby greater maternal anxiety and depressive symptoms at age 3 years were significantly associated with greater relative right FAA in children at age 5 years, which, in turn, was significantly associated with greater child internalizing symptoms at age 7 years (ps<.001). There was no moderating effect of FAA on the association between maternal internalizing symptoms at age 5 years and child internalizing symptoms at age 7 years.

Conclusions

Greater right frontal asymmetry may be a neurophysiological mechanism that mediates the intergenerational transmission of internalizing symptoms.
Education as a Proxy for Cognitive Reserve: Moderating Effects on White Matter Hyperintensity Burden in Healthy Aging and Cognitive Decline
Authors: Elkana Odelia , Beheshti Iman ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2024

Background

Cognitive reserve, often approximated by levels of education, is thought to protect against the deleterious effects of brain pathology on cognitive function. White matter hyperintensities (WMHs) are commonly associated with aging and cognitive decline, and higher WMH burden has been linked to the progression from healthy cognitive status (HC) to mild cognitive impairment (MCI). Understanding how cognitive reserve, as indicated by education, influences the relationship between WMH burden and cognitive outcomes can provide valuable insights for interventions aimed at delaying cognitive decline.

Objective

This study investigates the moderating role of education, as a proxy for cognitive reserve, on the relationship between WMH burden and the transition from HC to MCI.

Methods

Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, focusing on participants classified as cognitively healthy at baseline. A total of 153 cognitively healthy adults at the baseline were split into two groups: one group (n=85) remained cognitively healthy for at least 7 years, while the other group (n=68) progressed to MCI within 7 years. A multiple linear regression model was used to examine the interaction between group membership, baseline age, education, and sex in predicting WMH loads. The primary focus was on the interaction between group membership and education to assess the protective effect of cognitive reserve.

Results

The regression model explained 18.5% of the variance in WMH load. The analysis revealed statistically significant interaction between group membership and education on WMH loads (Interaction term: β = -0.097, p = 0.047), indicating that higher education levels are associated with a reduced WMH burden among individuals who progressed to MCI. The main effect of education alone was not significant, nor were the interactions involving sex (p > 0.05).

Conclusion

These findings support the hypothesis that education, as a proxy for cognitive reserve, provides a protective effect against the accumulation of WMH burden in older adults. The results suggest that higher cognitive reserve may mitigate the impact of neurodegenerative processes, thereby delaying the transition from HC to MCI. This underscores the importance of educational attainment in the preservation of cognitive health during aging.
Evaluating and Comparing Measures of Aperiodic Neural Activity
Authors: Donoghue Thomas , Hammonds Ryan , Lybrand Eric , Washcke Leonhard , Gao Richard , Voytek Bradley
Published: September 2024

Neuro-electrophysiological recordings contain prominent aperiodic activity – meaning irregular activity, with no characteristic frequency – which has variously been referred to as 1/f (or 1/f-like activity), fractal, or ‘scale-free’ activity. Previous work has established that aperiodic features of neural activity is dynamic and variable, relating (between subjects) to healthy aging and to clinical diagnoses, and also (within subjects) tracking conscious states and behavioral performance. There are, however, a wide variety of conceptual frameworks and associated methods for the analyses and interpretation of aperiodic activity – for example, time domain measures such as the autocorrelation, fractal measures, and/or various complexity and entropy measures, as well as measures of the aperiodic exponent in the frequency domain. There is a lack of clear understanding of how these different measures relate to each other and to what extent they reflect the same or different properties of the data, which makes it difficult to synthesize results across approaches and complicates our overall understanding of the properties, biological significance, and demographic, clinical, and behavioral correlates of aperiodic neural activity. To address this problem, in this project we systematically survey the different approaches for measuring aperiodic neural activity, starting with an automated literature analysis to curate a collection of the most common methods. We then evaluate and compare these methods, using statistically representative time series simulations. In doing so, we establish consistent relationships between the measures, showing that much of what they capture reflects shared variance – though with some notable idiosyncrasies. Broadly, frequency domain methods are more specific to aperiodic features of the data, whereas time domain measures are more impacted by oscillatory activity. We extend this analysis by applying the measures to a series of empirical EEG and iEEG datasets, replicating the simulation results. We conclude by summarizing the relationships between the multiple methods, emphasizing opportunities for re-examining previous findings and for future work.
Regulatory logic and transposable element dynamics in nematode worm genomes
Authors: Fierst Janna L. , Eggers Victoria K.
Published: September 2024

Genome sequencing has revealed a tremendous diversity of transposable elements (TEs) in eukaryotes but there is little understanding of the evolutionary processes responsible for TE diversity. Non-autonomous TEs have lost the machinery necessary for transposition and rely on closely related autonomous TEs for critical proteins. We studied two mathematical models of TE regulation, one assuming that both autonomous tranposons and their non-autonomous relatives operate under the same regulatory logic, competing for transposition resources, and one assuming that autonomous TEs self-attenuate transposition while non-autonomous transposons continually increase, parasitizing their autonomous relatives. We implemented these models in stochastic simulations and studied how TE regulatory relationships influence transposons and populations. We found that only outcrossing populations evolving with Parasitic TE regulation resulted in stable maintenance of TEs. We tested our model predictions inCaenorhabditisgenomes by annotating TEs in two focal families, autonomous LINEs and their non-autonomous SINE relatives and the DNA transposonMutator. We found broad variation in autonomous - non-autonomous relationships and rapid mutational decay in the sequences that allow non-autonomous TEs to transpose. Together, our results suggest that individual TE families evolve according to disparate regulatory rules that are relevant in the early, acute stages of TE invasion.
Light-triggered protease-mediated release of actin-bound cargo from synthetic cells
Authors: Akter Mousumi , Moghimianavval Hossein , Luker Gary D. , Liu Allen P.
Published: September 2024

Synthetic cells offer a versatile platform for addressing biomedical and environmental challenges, due to their modular design and capability to mimic cellular processes such as biosensing, intercellular communication, and metabolism. Constructing synthetic cells capable of stimuli-responsive secretion is vital for applications in targeted drug delivery and biosensor development. Previous attempts at engineering secretion for synthetic cells have been confined to non-specific cargo release via membrane pores, limiting the spatiotemporal precision and specificity necessary for selective secretion. Here, we designed and constructed a protein-based platform termed TEV Protease-mediated Releasable Actin-binding protein (TRAP) for selective, rapid, and triggerable secretion in synthetic cells. TRAP is designed to bind tightly to reconstituted actin networks and is proteolytically released from bound actin, followed by secretion via cell-penetrating peptide membrane translocation. We demonstrated TRAP’s efficacy in facilitating light-activated secretion of both fluorescent and luminescent proteins. By equipping synthetic cells with a controlled secretion mechanism, TRAP paves the way for the development of stimuli-responsive biomaterials, versatile synthetic cell-based biosensing systems, and therapeutic applications through the integration of synthetic cells with living cells for targeted delivery of protein therapeutics.
Enhanced detection of RNA modifications and read mapping with high-accuracy nanopore RNA basecalling models
Authors: Diensthuber Gregor , Pryszcz Leszek P. , Llovera Laia , Lucas Morghan C. , Delgado-Tejedor Anna , Cruciani Sonia , Roignant Jean-Yves , Begik Oguzhan , Novoa Eva Maria
Published: September 2024

In recent years, nanopore direct RNA sequencing (DRS) became a valuable tool for studying the epitranscriptome, owing to its ability to detect multiple modifications within the same full-length native RNA molecules. Although RNA modifications can be identified in the form of systematic basecalling “errors” in DRS data sets,N6-methyladenosine (m6A) modifications produce relatively low “errors” compared with other RNA modifications, limiting the applicability of this approach to m6A sites that are modified at high stoichiometries. Here, we demonstrate that the use of alternative RNA basecalling models, trained with fully unmodified sequences, increases the “error” signal of m6A, leading to enhanced detection and improved sensitivity even at low stoichiometries. Moreover, we find that high-accuracy alternative RNA basecalling models can show up to 97% median basecalling accuracy, outperforming currently available RNA basecalling models, which show 91% median basecalling accuracy. Notably, the use of high-accuracy basecalling models is accompanied by a significant increase in the number of mapped reads—especially in shorter RNA fractions—and increased basecalling error signatures at pseudouridine (Ψ)- andN1-methylpseudouridine (m1Ψ)-modified sites. Overall, our work demonstrates that alternative RNA basecalling models can be used to improve the detection of RNA modifications, read mappability, and basecalling accuracy in nanopore DRS data sets.
A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma
Authors: Müller Jan , Hartwig Christina , Sonntag Mirko , Bitzer Lisa , Adelmann Christopher , Vainshtein Yevhen , Glanz Karolina , Decker Sebastian O. , Brenner Thorsten , Weber Georg F. , von Haeseler Arndt , Sohn Kai
Published: September 2024

Here, we present a method for enrichment of double-stranded cfDNA with an average length of ∼40 bp from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we find significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA methylation, positively with H3K4me3 histone modifications and gene transcription. The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not yet been recognized. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with postoperative controls, we identify 136 and 241 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis, demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.
The Study of Sensorimotor Circuit Assembly inDrosophila melanogasterEmbryos and Larvae
Authors: Wreden Chris C. , Heckscher Ellie S.
Published: September 2024

In animals, movement is generated by the activity of motor circuits housed in the vertebrate spinal cord or the arthropod nerve cord. How motor circuits form is a fundamental question, with wide-ranging impacts on the fields of development, neurobiology, medicine, evolution, and beyond. Until recently, studying circuit assembly had been experimentally difficult, with a paucity of suitable models. Due to the introduction of novel neuroscience tools (calcium imaging, optogenetics, connectomics),Drosophilaembryos and larvae can be used as models to study motor circuit assembly. Here, we briefly review the knowledge relevant to motor circuit assembly inDrosophilalarvae. We discuss the larval body and its movements, larval neurons and circuits in the motor system, and how the generation of neural diversity starting from stem cells relates to circuit formation. The long-term goal ofDrosophilaresearch in this field is to identify developmental rules, determine when the rules apply, generate an integrated understanding of motor circuit development, and uncover molecular mechanisms driving the assembly process. Motor circuits are an ancient part of the nervous system, and so far, the developmental programs guiding motor circuit assembly appear to be largely conserved across phyla. Thus, as methods improve in other systems, findings inDrosophilawill provide foundational concepts that will inspire hypotheses in those systems.
Effect of anisotropy on the formation of heavy quarkonium bound states
Authors: Carrington Margaret E. , Kunstatter Gabor , Mukherjee Arghya
Published: September 2024

We study the real part of the static potential of a heavy quark-antiquark system in an anisotropic plasma medium. We use a quasiparticle approach where the collective dynamics of the plasma constituents is described using hard-loop perturbation theory. The parton distribution function is characterized by a set of parameters that can accurately describe the anisotropy of the plasma produced in a heavy ion collision. We calculate the potential numerically in strongly anisotropic systems and study the angular dependence of the distortion of the potential relative to the isotropic one. We obtain an analytic expression for the real part of the heavy quark potential in the limit of weak anisotropy using a model that expresses the potential in terms of effective screening masses that depend on the anisotropy parameters and the orientation of the quark-antiquark pair. A one-dimensional potential is formulated in terms of angle averaged screening masses that incorporate the anisotropy of the medium into a radial coordinate. We solve the corresponding Schrödinger equation and show that the magnitude of the binding energy typically increases with anisotropy. Anisotropy can play an important role, especially in states with nonzero angular momentum. This means that the number of bound states that are formed could depend on specific characteristics of the anisotropy of the plasma. Our study suggests that plasma anisotropy plays an important role in the dynamics of heavy quarkonium and motivates further study.

Published by the American Physical Society
2024
One dimensional staggered bosons, clock models, and their noninvertible symmetries
Authors: Berenstein David , Lloyd P. N. Thomas
Published: September 2024

We study systems of staggered boson Hamiltonians in a one dimensional lattice and in particular how the translation symmetry by one unit in these systems is in reality a noninvertible symmetry closely related to T-duality. We also study the simplest systems of clock models derived from these staggered boson Hamiltonians. We show that the noninvertible symmetries of these lattice models together with the discrete ZN symmetry predict that these are critical points with a U(1) current algebra at c=1 and radius 2N whenever N>4. We also present an independent computation of this value that arises directly from the staggered boson variables and does not use these additional symmetries. We also present a theoretical estimate of the values of critical coupling constants away from the self-dual symmetry point in these clock models.

Published by the American Physical Society
2024
Reinforcing mindware or supporting cognitive reflection: Testing two strategies for addressing a persistent learning challenge in the context of air resistance
Authors: Lindsey Beth A. , Boudreaux Andrew , Rosen Drew J. , Stetzer MacKenzie R. , Kryjevskaia Mila
Published: September 2024

In this study, we have explored the effectiveness of two instructional approaches in the context of the motion of objects falling at terminal speed in the presence of air resistance. We ground these instructional approaches in dual-process theories of reasoning, which assert that human cognition relies on two thinking processes. Dual-process theories suggest multiple possible avenues by which instruction might impact student reasoning. In this paper, we compare two possible instructional approaches: one designed to reinforce the normative approach (improving the outputs of the intuitive process) and another that guides students to reflect on and analyze their initial ideas (supporting the analytic process). The results suggest that for students who have already demonstrated a minimum level of requisite knowledge, instruction that supports analysis of their likely intuitive mental model leads to greater learning benefits in the short term than instruction that focuses solely on providing practice with the normative mindware. These results have implications for the design of instructional materials and help to demonstrate how dual-process theories can be leveraged to explain the success of existing research-based materials.

Published by the American Physical Society
2024
An efficient concrete plastic damage model for crack propagation in gravity dams during seismic action
Authors: Nghia-Nguyen Trong , Thanh Cuong Le , Khatir Samir , Hoang Le Minh , Chaiyaput Salisa , Abdel Wahab Magd
Published: September 2024

Purpose

Concrete gravity dams are important structures for flood control and hydraulic power generation, but they can be vulnerable to seismic activity due to ground movements that trigger crack propagation.

Design/methodology/approach

To better understand the factors that affect the stability of concrete gravity dams against concrete fracture during earthquakes, a concrete plastic damage model has been utilized with two new expressions to simulate compressive and tensile damage variables.

Findings

The findings showed that the crack patterns were strongly influenced by the concrete’s strength. The simulation results led to the proposal of appropriate concrete properties aimed at minimizing damage. These findings, together with the proposed model, offer significant insights that can enhance the safety and stability of concrete gravity dam structures.

Originality/value

This study offers a comprehensive analysis of concrete behavior under varying grades and introduces simple and robust expressions for evaluating concrete parameters in plastic damage models. The versatility of these expressions enables accurate simulation of stress-strain curves for different grades, resulting in excellent agreement between model results and experimental findings. The simulation of the Koyna Dam case study demonstrates a similarity in crack patterns with previous simulations and field observations.
Analyzing generation Z’s intentions to support sustainable tourism development in Nha Trang
Authors: Hoang Long Cuu , Nguyen Ha Duy
Published: September 2024

Purpose

This study aims to examine the determinants of Generation Z's intention to support sustainable development in tourism, with a focus on Nha Trang, Vietnam (a coastal city with famous tourism activities).

Design/methodology/approach

The study was conducted with an aid of SPSS 20.0 and SmartPLS 4.0 softwares to analyze the data collected from 394 valid respondents in Ho Chi Minh City through a cross-sectional method with a self-administered survey.

Findings

Empirical evidence revealed that sustainable tourism attitude, sustainable tourism belief and perceived sustainable destination image positively influenced Generation Z's support intentions toward sustainable tourism. In addition, perceived sustainable destination image also indirectly impacted intention to support sustainable tourism through the sustainable tourism attitude and/or belief (both single and sequential mediations).

Originality/value

This is among pioneering studies to figure out that knowledge negatively moderated the relationship between sustainable tourism attitude and intention to support sustainable tourism.
A lightweight passive ankle exoskeleton adjusted stiffness by shape memory alloy
Authors: Ge Jiao , Zhang Jiaqi , Chen Daheng , Dong Tiesheng
Published: September 2024

Purpose

The purpose of this paper is to actively calibrate power density to match the application requirements with as small an actuator as possible. So, this paper introduces shape memory alloy to design variable stiffness elements. Meanwhile, the purpose of this paper is also to solve the problem of not being able to install sensors on shape memory alloy due to volume limitations.

Design/methodology/approach

This paper introduces the design, modeling and control process for a variable stiffness passive ankle exoskeleton, adjusting joint stiffness using shape memory alloy (SMA). This innovative exoskeleton aids the human ankle by adapting the precompression of elastic components by SMA, thereby adjusting the ankle exoskeleton’s integral stiffness. At the same time, this paper constructs a mathematical model of SMA to achieve a dynamic stiffness adjustment function.

Findings

Using SMA as the driving force for stiffness modification in passive exoskeletons introduces several distinct advantages, inclusive of high energy density, programmability, rapid response time and simplified structural design. In the course of experimental validation, this ankle exoskeleton, endowed with variable stiffness, proficiently executed actions like squatting and walking and it can effectively increase the joint stiffness by 0.2 Nm/Deg.

Originality/value

The contribution of this paper is to introduce SMA to adjust the stiffness to actively calibrate power density to match the application requirements. At the same time, this paper constructs a mathematical model of SMA to achieve a dynamic stiffness adjustment function.
Ternary blended concrete strength evaluation: experimental and artificial intelligence techniques
Authors: Oyebisi Solomon , Shammas Mahaad Issa , Owamah Hilary , Oladeji Samuel
Published: September 2024

Purpose

The purpose of this study is to forecast the mechanical properties of ternary blended concrete (TBC) modified with oyster shell powder (OSP) and shea nutshell ash (SNA) using deep neural network (DNN) models.

Design/methodology/approach

DNN models with three hidden layers, each layer containing 5–30 nodes, were used to predict the target variables (compressive strength [CS], flexural strength [FS] and split tensile strength [STS]) for the eight input variables of concrete classes 25 and 30 MPa. The concrete samples were cured for 3–120 days. Levenberg−Marquardt's backpropagation learning technique trained the networks, and the model's precision was confirmed using the experimental data set.

Findings

The DNN model with a 25-node structure yielded a strong relation for training, validating and testing the input and output variables with the lowest mean squared error (MSE) and the highest correlation coefficient (R) values of 0.0099 and 99.91% for CS and 0.010 and 98.42% for FS compared to other architectures. However, the DNN model with a 20-node architecture yielded a strong correlation for STS, with the lowest MSE and the highest R values of 0.013 and 97.26%. Strong relationships were found between the developed models and raw experimental data sets, with R2 values of 99.58%, 97.85% and 97.58% for CS, FS and STS, respectively.

Originality/value

To the best of the authors’ knowledge, this novel research establishes the prospects of replacing SNA and OSP with Portland limestone cement (PLC) to produce TBC. In addition, predicting the CS, FS and STS of TBC modified with OSP and SNA using DNN models is original, optimizing the time, cost and quality of concrete.
High‐sensitivity C‐reactive protein to high‐density lipoprotein cholesterol ratio predicts long‐term adverse outcomes in patients who underwent percutaneous coronary intervention: A prospective cohort study
Authors: Dai Xin‐Ya , Xue Zheng‐Kai , Wang Xiao‐Wen , Chen Kang‐Yin , Hu Su‐Tao , Tse Gary , Rha Seung‐Woon , Liu Tong
Published: September 2024

High‐sensitivity C‐reactive protein (hsCRP) to high‐density lipoprotein cholesterol (HDL‐C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long‐term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study. Patients with CAD who underwent PCI at the Korea University Guro Hospital‐Percutaneous Coronary Intervention (KUGH‐PCI) Registry since 2004 were included. Patients were categorized into tertiles according to their CHR. The end points were all‐cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan–Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) and sensitivity analyses were performed. A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830–3.782, N = 1085) and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively greater risks of ACM, CM and MACEs (log‐rank, p < 0.001). Multivariate Cox regression showed that patients in the highest tertile had greater risks of ACM (HR: 2.127 [1.452–3.117]), CM (HR: 3.575 [1.938–6.593]) and MACEs (HR: 1.337 [1.089–1.641]) than those in the lowest tertile. RCS analyses did not reveal a significant non‐linear relationship between CHR and ACM, CM or MACEs. The significant associations remained significant in the sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data. Elevated CHR is a novel, independent risk factor for long‐term ACM, CM and MACEs in CAD patients following PCI.
The contributions of primary sources to fauna and the trophic structure in tropical seagrass areas: A case study from Thai waters
Authors: Tuntiprapas Piyalap , Hayashizaki Ken‐ichi , Prathep Anchana
Published: September 2024

Seagrass provides habitat and resources for various organisms in coastal areas. However, the productivity of a seagrass meadow might vary by its size, which can influence the contribution of primary sources to fauna and the food web structure. This study uses stable isotopes to investigate the contribution of sources to faunas and the associated food web structure in two tropical seagrass meadows. The carbon (δ13C) and nitrogen (δ15N) stable isotopes of primary sources such as mangrove leaf, coastal and riverine particulate organic matter, seagrass material and associated fauna (fish, bivalves, gastropods, crab, shrimp) were investigated from samples collected seagrass meadows of different sizes, at Libong Island and Tharai Island in Thailand. The contribution of the primary sources to the fauna diet showed that seagrass material was the main food source for fauna in both sites. Moreover, the trophic niche did not overlap among the groups of each fauna guild, reflecting the support seagrass provides to resident fauna. The study emphasizes the important role of seagrass as a habitat and feeding ground in tropical coastal ecosystems.