bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of cortico-muscular coupling associated with split-belt locomotor adaptation
Authors: Oshima Atsushi , Yokoyama Hikaru , Kaneko Naotsugu , Takahashi Ryogo , Takiyama Ken , Nakazawa Kimitaka 
Published: September 2024

AbstractHumans can adjust their walking patterns according to the demands of their internal and external environments, referred to as locomotor adaptation. Although significant functional coupling (i.e. cortico-muscular coherence [CMC]) has been shown between cortical and lower-limb muscle activity during steady-state walking, little is known about CMC in locomotor adaptation. Therefore, we investigated the adaptation-dependent modulation of the CMC between the sensorimotor region and the tibialis anterior muscle using a split-belt locomotor adaptation paradigm that can impose an asymmetric perturbation. We hypothesized that the CMC would temporarily decrease after exposure to the asymmetric perturbation and removal of the perturbation because of a mismatch between the predicted and actual sensory feedback. We also hypothesized that the CMC would increase as adaptation and de-adaptation to perturbation progressed because the motor system could become able to predict sensory feedback. Our findings revealed that the CMC temporarily decreased after exposure to and removal of the perturbation. Moreover, the CMC increased with adaptation and de-adaptation to perturbation. Although these results depend on the leg, frequency bands, and gait phases, they partially support our hypothesis. These findings suggest that flexible updating of cortico-muscular coupling in the motor system is a key mechanism underlying locomotor adaptation in humans. The results from our study on healthy young individuals contribute to the understanding of neuromuscular control of gait and provide valuable insight for optimising gait rehabilitation.Key pointsLocomotor adaptation plays a crucial role in our daily activities and gait rehabilitation.Although knowledge regarding the brain and muscle activities associated with locomotor adaptation has been accumulated, little is known about the functional coupling of the brain and muscle activities.Using high-density EEG and lower limb EMG, we demonstrated the modulation of cortico-muscular coherence between the sensorimotor region and the tibialis anterior muscle with adaptation and de-adaptation during a split-belt treadmill walking paradigm.Our findings suggest that flexible updating of cortico-muscular coupling in the motor system underlies locomotor adaptation in humans.Understanding the human brain’s control of muscles during split-belt locomotor adaptation will deepen our knowledge of neuromuscular control of gait and provide valuable insights for gait rehabilitation.
Bone adhered soil as a source of target and environmental DNA and proteins
Authors: de-Dios Toni , Bonucci Biancamaria , Barbieri Rémi , Kushniarevich Alena , D’Atanasio Eugenia , Dittmar Jenna M , Cessford Craig , Solnik Anu , Robb John E. , Warinner Christina , Oras Ester , Scheib Christiana L. 
Published: September 2024

AbstractIn recent years, sediments from cave environments have provided invaluable insights into ancient hominids, as well as past fauna and flora. Unfortunately, locations with favourable conditions for ancient DNA (aDNA) preservation in sediments are scarce. In this study we analysed a set of samples obtained from soil adhered to different human skeletal elements, originating from Neolithic to Medieval sites in England, and performed metagenomics and metaproteomics analysis. From them, we were able to recover aDNA sequences matching the genomes of endogenous gut and oral microbiome bacteria. We also found the presence of genetic data corresponding to animals and plants. In particular we managed to retrieve the partial genome and proteome of a Black Rat (Rattus rattus), sharing close genetic affinities to other medievalRattus rattus. Furthermore, we have also been able to reconstruct a partial human genome. The genetic profile of those human sequences matches the one recovered from the original skeletal element. Our results demonstrate that material usually discarded, as it is soil adhering to human remains, can be used to get a glimpse of the environmental conditions at the time of the death of an individual, even in contexts where due to harsh environmental conditions, the skeletal remains themselves are not preserved.
Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids
Authors: Capendale Pamela E. , Ambikan Anoop T. , García-Rodríguez Inés , Vieira de Sá Renata , Pajkrt Dasja , Wolthers Katja C. , Neogi Ujjwal , Sridhar Adithya 
Published: September 2024

SummaryParechovirus ahumpari 3 (HPeV-3), is among the main agents causing severe neonatal neurological infections such as encephalitis and meningitis. However, the underlying molecular mechanisms and changes to the host cellular landscape leading to neurological disease has been understudied. Through quantitative proteomic analysis of HPeV-3 infected neural organoids, we identified unique metabolic changes following HPeV-3 infection that indicate immunometabolic dysregulation. Protein and pathway analyses showed significant alterations in neurotransmission and potentially, neuronal excitotoxicity. Elevated levels of extracellular glutamate, lactate dehydrogenase (LDH), and neurofilament light (NfL) confirmed glutamate excitotoxicity to be a key mechanism contributing to neuronal toxicity in HPeV-3 infection and can lead to apoptosis induced by caspase signaling. These insights are pivotal in delineating the metabolic landscape following severe HPeV-3 CNS infection and may identify potential host targets for therapeutic interventions.
ProtRNA: A Protein-derived RNA Language Model by Cross-Modality Transfer Learning
Authors: Zhang Ruoxi , Ma Ben , Xu Gang , Ma Jianpeng 
Published: September 2024

AbstractProtein language models (PLM), such as the highly successful ESM-2, have proven to be particularly effective. However, language models designed for RNA continue to face challenges. A key question is: can the information derived from PLMs be harnessed and transferred to RNA? To investigate this, a model termed ProtRNA has been developed by cross-modality transfer learning strategy for addressing the challenges posed by RNA’s limited and less conserved sequences. By leveraging the evolutionary and physicochemical information encoded in protein sequences, the ESM-2 model is adapted to processing "low-resource" RNA sequence data. The results show comparable or even superior performance in various RNA downstream tasks, with only 1/8 the trainable parameters and 1/6 the training data employed by other baseline RNA language models. This approach highlights the potential of cross-modality transfer learning in biological language models.
IFN-I signaling in type 2 conventional dendritic cells supports TH2 and T follicular helper differentiation after allergen immunization
Authors: Webb Greta R , Hilligan Kerry L , Old Sam I , Tang Shiau-Choot , Lamiable Olivier , Ronchese Franca 
Published: September 2024

AbstractType 2 dendritic cells (DC2s) are essential for TH2 differentiation, but the signaling pathways involved in allergen sensing, DC activation and instruction of CD4+ T cell priming remain unclear. Previous transcriptomic analyses demonstrated a type-I interferon (IFN-I) signature in skin cDC2s following immunization with non-viable larvae ofNippostrongylus brasiliensis(Nb), house dust mite (HDM), andSchistosomaegg antigen (SEA). Blocking IFN-I signaling with anti-IFNAR1 (aIFNAR1) led to reduced TH2 cytokine responses to these antigens, however, the phenotype of cytokine-producing CD4+ T cells was not further defined. Here we show that conditional loss of IFNAR1 signaling in CD11c+ DCs significantly impaired effector TH2 and TFH CD4+ T cell responses toNb.In vivoproliferation experiments demonstrated reduced numbers of highly divided CD4+ T cells in IFNAR1ΔCD11cmice compared to IFNAR1WT, with the highly divided population comprising both TH2 and TFH. Characterization of the cDC2 compartment by flow cytometry and bulk RNAseq demonstrated lower numbers ofNb+ cDC2s in the skin-draining LN and a reduced expression ofIl15andIl15Rain IFNAR1ΔCD11cmice compared to IFNAR1WT, while expression of costimulatory molecules including CD80, CD86,Cd40andPdcd1lg2(PD-L2) was not impaired. Therefore, IFN-I conditioning of skin cDC2s is necessary for their effective priming of CD4+ T cell responses to allergens, providing evidence for a role of tissue cytokines in driving cDC2 activation in a TH2 context.
Enantiomeric histidine-rich peptide coacervates enhance antigen delivery to T cells
Authors: Pramanik Ushasi , Das Anirban , Brown Elise M. , Struckman Heather L. , Wang Huihao , Stealey Samuel , Sprunger Macy L. , Wasim Abdul , Fascetti Jonathan , Mondal Jagannath , Silva Jonathan R. , Zustiak Silviya P. , Jackrel Meredith E. , Rudra Jai S. 
Published: September 2024

SUMMARYPeptides and peptidomimetics that self-assemble via LLPS have recently emerged as building blocks for fabricating functional biomaterials due to their unique physicochemical properties and dynamic nature. One of life’s most distinctive signatures is its selectivity for chiral molecules and, to date, coacervates comprised of D-amino acids have not been reported. Here, we demonstrate that histidine-rich repeats of (GHGXY)4(X=L/V/P) and their enantiomers undergo LLPS opening new avenues for enhancing coacervate stability. Through a series of biophysical studies, we find that LLPS kinetics, droplet size, fusion, and encapsulation efficiency are dictated by the primary sequence. Further, these coacervates can encapsulate therapeutic cargo which are then internalized via endocytic mechanisms. Finally, we show that the coacervates enhance antigen presentation to CD4+and CD8+T cells resulting in robust proliferation and production of functional cytokines. Collectively, our study describes the development and characterization of enantiomeric peptide coacervates as attractive vaccine delivery vehicles with tunable physicochemical properties.HIGHLIGHTSD amino acid-peptides were used for the first time to construct phase separating coacervatesChirality does not restrict LLPS or modulate other coacervate propertiesAntigen delivery using chiral coacervates enhances and prolongs presentation to T cellsPROGRESS AND POTENTIALPeptides can undergo self-assembly via liquid-liquid phase separation (LLPS) to result in solute-rich coacervates that can serve as biomaterials. Using histidine-rich peptide repeats, this work demonstrates that peptides composed of entirely D-amino acids can form functional coaceravtes. The kinetics of LLPS and bulk properties of the droplets can be controlled through simple amino acid substitutions. The coacervates, while immunologically inert, exert an adjuvanting effect and enhance antigen presentation to T cells leading to proliferation and functional cytokine production. The materials showcased here possess high translational potential for combined delivery of immunomodulators and antigens for vaccine delivery against infectious diseases or cancer. The deliverables from this study will also inspire the development of chiral systems that will contribute to the knowledge of cellular processes associated with phase changes integral to both physiology and pathology.
Foot placement control underlies stable locomotion across species
Authors: De Comite Antoine , Seethapathi Nidhi 
Published: September 2024

AbstractAnimals navigate their environment stably without inefficient course corrections despite unavoidable errors. In humans and some robots, this stability is achieved by controlling the placement of the foot on the ground such that recent movement errors are corrected. However, it is unknown whether and how animals with diverse nervous systems and body mechanics use such foot placement control: foot trajectories of many-legged animals are considered as stereotypical velocity-driven patterns, as opposed to error-driven. Here, we posit a control structure for stabilizing foot placement in any legged embodiment by unifying velocity-driven and body state-driven contributions, and develop a framework to discover control strategies used across species from natural locomotor variability. Using this framework, we find evidence for body state-dependent foot placement control in flies and mice, previously only shown to exist in humans. We discover that the urgency and centralization of the foot placement control strategy is shaped by the animal’s neuromechanical embodiment. More inherently stable many-legged embodiment is associated with a lower control magnitude and timescale. Further, many-legged embodiment is accompanied by decentralized control with modular control functions, timescales, and gains, whereas analogous functions are centralized across both legs in humans. Our approach discovers signatures of stabilizing control across species and reveals how different neuromechanical embodiments achieve a shared functional goal: foot placement control.
Causality Analysis of Protein Corona Composition: Phosphatidylcholine-Enhances Plasma Proteome Profiling by Proteomics
Authors: Rafieioskouei Arshia , Rogale Kenneth , Saei Amir Ata , Mahmoudi Morteza , Bonakdarpour Borzoo 
Published: September 2024

AbstractThe study of the protein corona, the immediate and evolving biomolecular coating that forms on the surface of nanoparticles when exposed to a biological environment, is a crucial area in nanomedicine. This phenomenon significantly influences the behavior, functionality, and biological interactions of nanoparticles with biosystems. Until now, conclusions regarding the role of the protein corona in specific biological applications have been based on establishingcorrelationrather thancausation. By understanding causality, researchers can predict how changes in nanoparticle properties or biological conditions will affect protein corona composition, in turn affecting the nanoparticle interactions with the biosystems and their applications. This predictive capability is essential for designing nanoparticles with specific characteristics tailored for therapeutic and diagnostic nanomedicine applications. Here, we explore the concept of “actual causality” (by Halpern and Pearl) to mathematically prove how various small molecules, including metabolites, lipids, vitamins, and nutrients, spiked into plasma can induce diverse protein corona patterns on identical nanoparticles. This approach significantly enhances the depth of plasma proteome profiling. Our findings reveal that among the various spiked small molecules, phosphatidylcholine was the actual cause of the observed increase in the proteomic depth of the plasma sample. By considering the concept of causality in the field of protein corona, the nanomedicine community can substantially improve their ability to design safer and more efficient nanoparticles for both diagnostic and therapeutic purposes.
ScReNI: single-cell regulatory network inference through integrating scRNA-seq and scATAC-seq data
Authors: Xu Xueli , Liang Yanran , Tang Miaoxiu , Wang Jiongliang , Wang Xi , Li Yixue , Wang Jie 
Published: September 2024

ABSTRACTSingle cells exhibit heterogeneous gene expression profiles and chromatin accessibility, measurable separately via single-cell RNA sequencing (scRNA-seq) and single-cell transposase chromatin accessibility sequencing (scATAC-seq). Consequently, each cell possesses a unique gene regulatory network. However, limited methods exist for inferring cell-specific regulatory networks, particularly through the integration of scRNA-seq and scATAC-seq data. Here, we develop a novel algorithm named single-cell regulatory network inference (ScReNI), which leveragesk-nearest neighbors and random forest algorithms to integrate scRNA-seq and scATAC-seq data for inferring gene regulatory networks at the single-cell level. ScReNI is built to analyze both paired and unpaired datasets for scRNA-seq and scATAC-seq. Using these two types of single-cell sequencing datasets, we validate that a higher fraction of regulatory relationships inferred by ScReNI are detected by chromatin immunoprecipitation sequencing (ChIP-seq) data. ScReNI shows superior performance in network-based cell clustering when compared to existing single-cell network inference methods. Importantly, ScReNI offers the unique function of identifying cell-enriched regulators based on each cell-specific network. In summary, ScReNI facilitates the inferences of cell-specific regulatory networks and cell-enriched regulators.
Influence of the Glymphatic System on α-Synuclein Propagation: Role of Aquaporin-4 and the Dystrophin-Associated Protein Complex
Authors: Lopes Douglas M , Llewellyn Sophie K , Bury Sheila E , Wang Jiazheng , Wells Jack A , Gegg Matthew E , Verona Guglielmo , Lythgoe Mark F , Harrison Ian F 
Published: September 2024

AbstractPropagation and aggregation of prion proteins, such as tau and α-synuclein (αSyn), are key pathological features of neurodegenerative diseases. Extracellular clearance pathways, such as the glymphatic system, may play a crucial role in the removal of these toxic proteins from the brain. Primarily active during sleep, this system relies on aquaporin-4 (AQP4) water channel expression and polarisation to astrocytic endfeet, facilitating interstitial solute clearance. Glymphatic dysfunction has recently been implicated in Parkinson’s disease, however the precise mechanisms underlying the pathogenic effect of this dysfunction remain unclear. This includes how impaired glymphatic function influences αSyn propagation dynamics, and the role of propagating αSyn itself on glymphatic function.In this study, we used a mouse model of αSyn propagation to elucidate the impact of αSyn aggregation on glymphatic function, by measuring CSF-ISF exchange and assessing AQP4 and associated endfoot complex proteins in the brain over time and across different regions. Our results show that direct injection of αSyn pre-formed fibrils leads to reduced expression of the AQP4 endfoot complex, but propagation of endogenous αSyn induces an enhancement of glymphatic function suggesting compensatory upregulation in response to increasing endogenous αSyn load. To determine the influence of glymphatic dysfunction on αSyn propagation dynamics, we then employed a pharmacological approach to inhibit glymphatic function in this model. Acute glymphatic inhibition significantly reduced brain to CSF αSyn clearance, and chronic treatment exacerbated αSyn pathology, neurodegeneration, and motor behavioural deficits in mice. Together our findings show that αSyn clearance and propagation are modulated by glymphatic function and suggest that AQP4 complex dysregulation may contribute to glymphatic impairment associated with Parkinson’s diseases.Summary for the non-scientific communityThe glymphatic system clears brain waste during sleep. Lopes et al. show that α-synuclein, a protein linked to Parkinson’s, is cleared by this system. Using a mouse model of the disease, they suggest that aquaporin-4 water channels may impair glymphatic function, contributing to α-synuclein buildup in patients’ brains.
Intestinal helminth skews DC2 development towards regulatory phenotype to counter the anti-helminth immune response
Authors: Andrusaite Anna , Ridgewell Olivia , Ahlback Anna , Webster Holly , Yamaguchi Hiroki , Peel Molly , Frede Annika , Al-Khalidi Sarwah , Farthing Andrew , Heawood Anna , Smith Annabelle , Roberts Edward , Mowat Allan , Maizels Richard , Perona-Wright Georgia , Milling Simon 
Published: September 2024

AbstractThe intestinal immune system maintains a balance between active immunity needed for protection and tolerance towards harmless antigens. Dendritic cells (DCs) found in the intestinal mucosa are key to the adaptive arm of these immunoregulatory events. DCs sample antigens in the tissue and then migrate to the draining lymph nodes, where they prime the T cells that then migrate back to the tissue as effector or regulatory cells. Intestinal DC are highly heterogeneous, and it remains unclear exactly which subsets induces the different kinds of immune response, or what signalling molecules and cellular mechanisms are involved. Here, we have studied these issues usingHeligmosomoides polygyrus bakeri (Hpb)infection in mice, a model which is uniquely suited to dissecting this regulatory circuit in the gut, where it drives type 2 protective immunity at the same time as inhibiting other aspects of the immune response. Here, we characterise intestinal DC duringHpbinfection for the first time. We observed a dynamical change of intestinal DC populations throughout the course of infection that correlated with altered phenotype and function. In particular,Hpbinfection saw a rise in a population of CD103+DC2 that retained a potent ability to drive Tregs during the infection and unlike CD103-DC2, had a reduced ability to induce pro-inflammatory immune response. Furthermore, transcriptional analysis revealed that TGFβ signalling may be responsible for some of the changes observed. This was confirmedin vitro, where supplementation TGFβ orHpb-produced TGFβ mimic (TGM) replicated the immunomodulatory effects seen in DCsin vivo. Together, these results present a mechanistic explanation of how helminths such asHpbmay modulate host immune responses by altering the differentiation and function of local DCs. Furthermore, our work provides the basis for understanding immune homeostasis in the intestine at the molecular and cellular levels. Thus, this work fills out a crucial gap in our knowledge of basic biology underlining the DC decision between pro- and anti-inflammatory immune response in the central circuit of adaptive immune response.
Beneficial rhizobacteria and virus infection modulate the soybean metabolome and influence the feeding preferences of the virus vectorEpilachna varivestis
Authors: Pulido Hannier , Mauck Kerry E. , De Moraes Consuelo M. , Mescher Mark C. 
Published: September 2024

AbstractThere is growing evidence that microbial plant symbionts shape interactions between plants and other organisms by modulating gene expression and metabolism. However, the detailed mechanisms mediating such effects are not well understood, particularly in systems where plants interact simultaneously with multiple symbionts and antagonists. In this study, we employed a multi-factorial design to explore the individual and combined effects of two plant-beneficial rhizobacteria (Delftia acidovoransandBradyrhizobium japonicum) and a pathogen (Bean pod mottle virus: BPMV) on gene expression and metabolite production by soybean plants, as well as downstream effects on plant interactions with a beetle vector of BPMVEpilachna varivestis. Our results document microbial effects on basic metabolism and defense pathways, resulting in increased levels of primary metabolites and depletion of secondary metabolites. These changes are consistent with the observed feeding preferences of beetles for rhizobia-inoculated and virus-infected plants. Together, our results indicate that BPMV infection and rhizobacteria colonization cause dramatic changes in plant metabolites related to nutrition and defense, with significant consequences for an agriculturally important pathosystem.