bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Electrophysiology and Neuroimaging Approach in Assessing Disorders of Consciousness: A Multimodal Multicentric Machine Learning Study
Authors: Manasova Dragana , Louan Belloli Laouen Mayal , Rosenfelder Martin , Willacker Lina , Flo Rama Emilia , Valota Chiara , Hermann Bertrand , Kaufmann Brigitte Charlotte , Pirastru Alice , Derchi Chiara Camilla , Raiser Theresa , Valente Melanie , Sangare Aude , Türker Başak , Pyatigorskaya Nadya , Béranger Benoît , Colombo Michele , Munoz-Musat Esteban , Escrichs Anira , Atzori Tiziana , Baglio Francesca , Lapa Constantin , Berlis Ansgar , Krüger Kristina , Luther Tina , Perlbarg Vincent , Deco Gustavo , Sanz-Perl Yonathan , Tagliazucchi Enzo , Puybasset Louis , Rohaut Benjamin , Naccache Lionel , Comanducci Angela , Arzi Anat , Rosanova Mario , Bender Andreas , Sitt Jacobo Diego 
Published: November 2024

AbstractSeverely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness (DoC). This spectrum includes clinical categories such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioral assessment of consciousness can often be deceptive.To bridge this dissociation, neuroimaging techniques are employed to look for the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation - functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessment through interpretable machine learning (ML). The electrophysiological modalities included high-density electroencephalography (EEG) (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional magnetic resonance imaging (MRI), diffusion MRI, and 18F-fluoro-deoxy-glucose positron emission tomography (FDG PET).Our investigation reveals that specific modalities, such as functional assessments provide comprehensive insights into the currently evaluated state of consciousness - the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient’s evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centers with different acquisition parameters. Importantly, we show that there is an improved model performance with the increase in the number of modalities. We observe a higher inter-modality disagreement for MCS patients and those patients who improve. Lastly, we observe a difference in feature importances in diagnosis and prognosis.This integrative multimodal and ML methodology presents a promising avenue for a more nuanced understanding of DoC, contributing to enhanced diagnostic precision and prognostic capabilities in clinical practice.
Mapping the endosomal proximity proteome reveals Retromer as a hub for RAB GTPase regulation
Authors: Antón-Plágaro Carlos , Chen Kai-en , Guo Qian , Liu Meihan , Evans Ashley J. , Lewis Philip A. , Heesom Kate J , Wilkinson Kevin A. , Collins Brett M. , Cullen Peter J. 
Published: November 2024

ABSTRACTEndosomal retrieval and recycling of integral cargo proteins is essential for cell, tissue and organism-level development and homeostasis and is orchestrated through a specialised retrieval sub-domain on the endosomal vacuole. However, although sub-domain dysfunction is associated with human disease our appreciation of the molecular details and functional components of the retrieval sub-domain(s) remains poorly described. Here, using comparative proximity proteomics of critical retrieval sub-domain components Retromer and Retriever, their cargo adaptors, and a component of the opposing ESCRT-degradative sub-domain, we provide a data-rich resource that identifies new molecular details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface of Retromer with RAB GTPases. Combining X-ray crystallography and in silico predictions with extensive biochemical and cellular analysis, we dissect the direct association of Retromer with RAB10 regulators DENND4A, DENND4C, TBC1D1, and TBC1D4, and the RAB35 regulator TBC1D13. Overall, we conclude that the Retromer retrieval sub-domain constitutes a major hub for the regulated switching of selected RAB GTPases and propose that this constitutes a major component of the role of Retromer in neuroprotection.
Task-induced internal bodily rather than brain states regulate human self-perception
Authors: Xie Musi , Bao Han , Wu Hang , Zhang Yihui , Liu Yueyao , Han Junrong , Zhang Xilin , Qin Pengmin 
Published: November 2024

AbstractA fundamental ability for us is to identify and distinguish with others, known as the self, whose neural substrate is hard to identify by external self-related stimuli because of possible interference from internal self-related states of both body and brain. Using the same stimuli, we ruled out this dilemma by manipulating human subjects performing own- and celebrity-face discrimination tasks to induce self-related and non-self-related states, respectively. Results showed that stimulus-driven sensory sensory differences among own-, celebrity-, and stranger-faces were independent of task-induced internal states, whereas their perceptual differences were strongly modulated by these states. Intriguingly, we further found that subjects’ bodily (indexed by heartbeat-evoked potentials) rather than brain (indexed by pre-stimulus α-powers) states not only predicated their self-perception but also moderated the relationship between external stimuli and self-perception. Our results reveal for the first time an adaptive self-perception, shaped by not only external stimuli but also internal states, especially the interoception.
Clonal analysis of murine HSC self-renewal and differentiation in native hematopoiesis
Authors: You Chenyu , Zhang Zhen , Lin Li , Sun Jianlong 
Published: November 2024

AbstractHematopoietic stem cells (HSC) maintain lifelong hematopoiesis. However, in current clonal analyses with unbiased “barcoding” approaches, steady-state hematopoietic clones in young and middle-aged adults rarely have detectable HSCs, which precludes comprehensive interrogation of HSC clonal behaviors. In the current study, we used the previously described Sleeping Beauty transposon model to investigate HSC self-renewal and differentiation at a clonal level following a lifelong chase that significantly enriched HSC-derived clones. From seventeen mice, we detected over seventy thousand clones in native hematopoiesis that reflected the known HSC differentiation biases observed in transplantation. Our data indicated an intimate connection between megakaryocytic-restricted differentiation and HSC self-renewal expansion. By comparing the differentiation patterns of clones derived from transplanted HSCs, we further demonstrated the abilities of HSCs to preserve their cell fates towards self-renewal or multilineage differentiation. Unlike HSCs, clonal expansion in multipotent progenitors was associated with either a differentiation-active or differentiation-indolent state. Moreover, the clonal expansion events in the more differentiated stem and progenitor cells, but not the most primitive HSCs, drove clonal expansion in the megakaryocyte and myeloid cell lineages. Our study provided a comprehensive portrait of native hematopoiesis at a clonal level and revealed the general patterns in which HSCs maintained self-renewal and multi-lineage differentiation.
Transcallosal generation of phase aligned beta-bursts underlies TMS-induced interhemispheric inhibition
Authors: Georgiev Christian , Mongold Scott J. , Cabaraux Pierre , Naeije Gilles , Duque Julie , Bourguignon Mathieu 
Published: November 2024

AbstractBackgroundThe excitability of the sensorimotor (SM1) cortices is reflected in the bilateral ∼20 Hz beta oscillations. The extent to which these oscillations subtend the interhemispheric inhibition captured by the Transcranial Magnetic Stimulation (TMS) ipsilateral Silent Period (iSP) protocol is unknown.ObjectivesWe investigated the relationship between movement-induced beta suppression, iSP, and manual dexterity.MethodsForty adults underwent an Electroencephalography assessment of beta oscillations during volitional left hand movement and a TMS assessment of iSP recorded from the right hand. In both cases, left SM1 beta oscillations (contralateral to the activated right SM1), were monitored through a proxy signal – the Electromyography of the contracted right hand. Manual dexterity was assessed with the Purdue Pegboard Test.ResultsVolitional movement caused significant bilateral SM1 beta suppression in nearly all participants (≥ 85 %). ISPs were observed in every participant. In the proxy signal for the left SM1, the iSP coincides with TMS-induced high-amplitude beta bursts. These bursts showed significant phase alignment across participants 10–70 ms after the TMS pulse. There was no significant association between the left-/right-hemisphere beta suppression, iSP, and manual dexterity.ConclusionOur results highlight the distinct nature of beta oscillation changes during voluntary movement compared to TMS-iSP and show that TMS induces IHI via transcallosal induction of phase aligned beta bursts. Furthermore, our data suggests that only the initial phase of a beta burst carries an inhibitory effect. It also highlights the possibility of evoking a beta burst with the iSP protocol, opening perspectives for future modeling studies.Highlights-Movement-induced beta suppression does not reflect Transcranial Magnetic Stimulation-induced interhemispheric inhibition-Transcranial Magnetic Stimulation induces interhemispheric inhibition via transcallosal induction of phase aligned high-amplitude beta bursts-The inhibitory effect of a beta burst appears to be carried by its initial oscillatory cycle-Beta oscillations and interhemispheric inhibition’s role for motor dexterity need further exploration
Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity
Authors: Lazarova Mariya , Eicher Thomas , Börnsen Clara , Zeng Hui , Athar Mohd , Okada Ui , Yamashita Eiki , Spannaus Inga M. , Borgosch Max , Cha Hi-jea , Vargiu Attilio V. , Murakami Satoshi , Diederichs Kay , Frangakis Achilleas S. , Pos Klaas M. 
Published: November 2024

SummaryAntibiotic efflux plays a key role for the multidrug resistance in Gram-negative bacteria1–3. Multidrug efflux pumps of the resistance nodulation and cell division (RND) superfamily function as part of cell envelope spanning systems and provide resistance to diverse antibiotics 4,5. Here, we identify two phylogenetic clusters of RND proteins with conserved binding pocket residues. Based on the characterisation of one representative of each cluster,K. pneumoniaeOqxB andE. coliAcrB, we show that the transfer of a single conserved residue between both clusters alters the resistance against a panel of structurally unrelated drugs. The substitution is not only associated with changes in the binding pocket architecture, but also alters the equilibrium between the conformational states of the transport cycle. We show that AcrB and OqxB adopt fundamentally different apo states that suggest different mechanisms of initial substrate binding and might determine the differences between the substrate preferences of both pumps. The observed conformational heterogeneity between different RND clusters is suggested to be phylogenetically conserved and might play a role for the diversification of the resistance phenotype between homologous RND multidrug efflux pumps.
IFNγ-Expressing Myeloid Cells Localize within Lipoproteinosis during Drug-Associated Pulmonary Alveolar Proteinosis occurring in Systemic Juvenile Idiopathic Arthritis
Authors: Delmastro Alea , Liu Candace C. , Ding Xiao-Wen , Tan Serena Y. , Averbukh Inna , Bosse Marc , Keyes Timothy J. , Sharma Surbhi , Deutsch Gail , Angelo Michael , Saper Vivian E. , Mellins Elizabeth D. , McCaffrey Erin F. 
Published: November 2024

SummaryIn the United States, approximately one in 1000 children are diagnosed with the autoinflammatory disease, Juvenile Idiopathic Arthritis (JIA). A subset of JIA cases manifests as Systemic JIA (sJIA), which is characterized by joint pain, fevers, rashes, and systemic inflammation. Severe pulmonary complications have not historically been associated with sJIA. Since 2010, inhibitors of interleukin-1 and interleukin 6 (IL-1i/IL-6i) are the recommended course of treatment for sJIA, yet recently studies show evidence of a severe drug hypersensitivity reaction implicating these medications in a subset of those treated. With this reaction, sJIA patients can develop severe lung disease, including pulmonary alveolar proteinosis (PAP). As this drug-associated lung disease has only recently been identified, the etiology of sJIA drug-associated PAP (sJIA-daPAP) is poorly understood. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to define the cellular immune infiltrate and describe pathological features of PAP in sJIA-daPAP patients. We found an enrichment of eosinophils, neutrophils, and M2 macrophages within regions of lipoproteinosis. These enriched subsets all upregulate IFNγ within lipoproteinosis, a signature specific to sJIA-daPAP samples compared to non-sJIA-PAP samples. In a cellular neighborhood analysis, we identified that eosinophils, neutrophils and M2 macrophages frequently co-localize within the same cellular microenvironment, especially in lipoproteinosis regions. Therefore, this spatial coordination may be involved in clearance or persistence of lipoproteinosis in sJIA-daPAP. This study provides a comprehensive overview of sJIA-daPAP immune pathology and suggests cellular mechanisms that drive inflammation in sJIA patients experiencing pulmonary complications associated with delayed drug hypersensitivity during IL-1i/IL-6i treatment.
Multimodal CRISPR screens uncover DDX39B as a global repressor of A-to-I RNA editing
Authors: Wei Tianzi , Li Jiaxuan , Lei Xiang , Lin Risheng , Wu Qingyan , Zhang Zhenfeng , Shuai Shimin , Tian Ruilin 
Published: November 2024

AbstractAdenosine-to-Inosine (A-to-I) RNA editing is a critical post-transcriptional modification that diversifies the transcriptome and influences various cellular processes. Despite its significance, the regulatory mechanisms controlling A-to-I editing remain largely unknown. In this study, we present two complementary CRISPR-based genetic screening platforms: CREDITS (CRISPR-basedRNAEDITing regulatorScreening), which enables genome-scale identification of editing regulators using an RNA recorder-based reporter system, and scCREDIT-seq (single-cellCRISPR-basedRNAEDITingsequencing), which provides multiplexed single-cell characterization of transcriptome and editome changes for pooled perturbations on dozens of selected genes. Through screening 1,350 RNA-binding proteins, we identified a series of known and novel A-to-I editing regulators. Detailed mechanistic investigation revealed DDX39B as a global repressor of A-to-I editing, which functions by preventing double-stranded RNA accumulation through its helicase and ATPase activities. We demonstrate that targeting DDX39B significantly enhances the efficiency of RNA editing-based tools like CellREADR and LEAPER, and represents a promising strategy for anti-HDV therapy by modulating viral genome editing. These technological advances not only expand our understanding of RNA editing regulation but also provide powerful tools for exploring tissue-specific and context-dependent RNA modification mechanisms, with broad implications for therapeutic development.
Computational analysis to assess hemodynamic forces in descending thoracic aortic aneurysms
Authors: Duca Francesca , Bissacco Daniele , Crugnola Luca , Faitini Chiara , Domanin Maurizio , Migliavacca Francesco , Trimarchi Santi , Vergara Christian 
Published: November 2024

AbstractDescending Thoracic Aortic Aneurysm (DTAA) is a life-threatening disorder, defined as a localized enlargement of the descending portion of the thoracic aorta. In this context, we develop a Fluid-Structure Interaction (FSI) computational framework, with the inclusion of a turbulence model and different material properties for the healthy and the aneurysmatic portions of the vessel, to study the hemodynamics and its relationship with DTAA.We first provide an analysis on nine ideal scenarios, accounting for different aortic arch types and DTAA ubications, to study changes in blood pressure, flow patterns, turbulence, wall shear stress, drag forces and internal wall stresses. Our findings demonstrate that the hemodynamics in DTAA is profoundly disturbed, with the presence of flow recirculation, formation of vortices and transition to turbulence. In particular, configurations with a more steep aortic arch exhibit a more chaotic hemodynamics. We notice also an increase of pressure values for configurations with less steep aortic arch and of drag forces for configurations with distal DTAA.Secondly, we replicate our analysis for three patient-specific cases (one for type of arch) obtaining conforting results in terms of accordance with the ideal scenarios. Finally, in a very preliminary way, we try to relate our findings to possible stent-graft migrations after TEVAR procedure to provide predictions on the post-operative state.KEY POINTSThis study employs computational methods to assess hemodynamic forces in descending thoracic aortic aneurysms;We consider ideal cases by varying aortic arch type and aneurysm location;Our results show: chaotic hemodynamics for steep aortic arches; increase of pressure values for less steep aortic arches; high risk of plaque in the sac for proximal aneurysms and in the neck for distal aneurysms;We analyse also 3 patient-specific cases, confirming the major outcomes found for the ideal cases;We try to suggest how our pre-operative findings may be put in relation to assess the risk of stent-graft migration of a possible TEVAR procedure.
Machine learning outcompetes human assessment in identifying eggs of a conspecific brood parasite
Authors: Hughes Anna E. , Mari Lisandrina , Troscianko Jolyon , Jelínek Václav , Albrecht Tomáš , Šulc Michal 
Published: November 2024

AbstractAvian brood parasitism provides an exceptional system for studying coevolution. While conspecific brood parasitism (CBP) is more common than interspecific parasitism, it is less studied due to the challenge of detecting parasitic eggs, which closely resemble those of the host. Although molecular genotyping can accurately detect CBP, its high cost has led researchers to explore egg appearance as a more accessible alternative. Barn swallows (Hirundo rustica) are considered conspecific brood parasites, but identifying parasitic eggs has traditionally relied on human visual assessment. Here, we used UV-visible photographs of non-parasitized barn swallow clutches and simulated parasitism to compare the accuracy of human assessment with automated methods. In two games, participants and models identified parasitic eggs from six or two options. While humans performed better than chance (72% and 87% accuracy), they still made significant errors. In contrast, the automated supervised model was far more reliable, achieving 95% and 97% accuracy. We think that the model outperformed humans due to its ability to analyse a broader range of visual information, including UV reflectance, which humans cannot perceive. We recommend using supervised models over human assessment for identifying conspecific parasitic eggs and highlight their potential to advance research on evolution of egg colouration.
Roquin exhibits opposing effects on RNA stem-loop stability through its two ROQ domain binding sites
Authors: Tants Jan-Niklas , Walbrun Andreas , Kollwitz Lucas , Friedrich Katharina , Rief Matthias , Schlundt Andreas 
Published: November 2024

ABSTRACTThe interaction of mRNA and regulatory proteins is critical for post-transcriptional control. For proper function, these interactions as well as the involved protein and RNA structures are highly dynamic and thus, mechanistic insights from structural biology are challenging to obtain. In this study, we employ a multifaceted approach combining single-molecule force spectroscopy with NMR spectroscopy to analyze the concerted interaction of the two RNA-binding interfaces (A-site, B-site) of the immunoregulatory protein Roquin’s ROQ domain with the 3’ untranslated region (UTR) of theOx40mRNA. This 3’UTR contains two specific hairpin structures termed constitutive and alternative decay elements (CDE, ADE), which mediate mRNA degradation via binding of Roquin. Our single-molecule experiments reveal the CDE folds cooperatively, while ADE folding involves at least 3 on-pathway and 3 off-pathway intermediates. Utilizing an integrated microfluidics setup allows to extract binding kinetics to Roquin in real time. Supported by NMR, we find opposing effects of the two Roquin sub-domains on distinct regions of the ADE: while the A-site interacts strongly with the folded apical stem-loop, we find that the B-site has a distinct destabilizing effect on the central stem of the ADE owed to single-strand RNA binding. We propose that RNA-motif nature and Roquin A- and B-sites jointly steer mRNA decay with context-encoded specificity, and we suggest plasticity of stem structures as key determinant for Roquin-RNA complex formation. The unique methodological combination of NMR and single-molecule force spectroscopy reveals an unknown mechanism of a dual-function RNA-binding domain suggesting a new model for target RNA recognition.SIGNIFICANCE STATEMENTLocal RNA structure is decisive for specific engagement with gene-regulatory proteins and, as a consequence, correct cellular function. However, its existence often appears dynamic and thus, challenging to study. This study shows how NMR and single-molecule force spectroscopy efficiently complement each other to provide high-resolution, time-resolved data on RNA folding intermediates during dynamic complex formation with the immune-regulating protein Roquin, which exploits multiple RNA-binding sites. Our data reveal a dual-mode binding of Roquin to RNA by firmly attaching to the stem-loop and, at the same time, destabilizing other regions making them accessible to downstream interaction partners.
HGTs are not SPRs: In the presence of ghost lineages, series of Horizontal Gene Transfers do not result in series of Subtree Pruning and Regrafting
Authors: Tannier Eric , Tricou Théo , Benali Syrine , de Vienne Damien M. 
Published: November 2024

AbstractWhen a gene is horizontally transferred (HGT), under the “replacement” model where the transferred gene replaces its homolog in the recipient genome, the corresponding gene phylogeny departs from the species phylogeny by a Subtree Prune and Regraft (SPR) operation: the recipient branch is moved from its initial position to attach to the donor branch. Based on this observation, various methods have used SPRs to simulate or infer HGTs. We examine this apparent equivalence in the light of ghost lineages,i.e. all related species absent from the phylogeny because they are extinct, unknown or have not been sampled. These absent species branches are much more numerous than the visible ones under most situations, so HGTs have great chances of originating from ghosts. We show that in this case, there is a high probability that series of HGTs do not correspond to series of SPRs. This biases the simulations under SPRs and prevents the inference under SPRs from retrieving the true transfers. For instance if the studied phylogeny represents 1% of all the species susceptible to exchange genetic material with the 100 sampled species, and 11 transfers occurred, then modelling HGTs with SPRs will be misleading in around 50% of the cases. This applies to a certain extent to other phylogenetic simulation or inference methods of HGT, like reconciliation.