bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-dimensional immunofluorescence atlas of the brain of the hackled-orb weaver spider,Uloborus diversus
Authors: Artiushin Gregory , Corver Abel , Gordus Andrew 
Published: September 2024

AbstractSpider orb-web building is a captivating, rare example of animal construction, whose neural underpinnings remain undiscovered. An essential step in understanding the basis of this behavior is a foundational mapping of the spider’s neuroanatomy, which has thus far been primarily studied using non-web building species. We created a three-dimensional atlas for the hackled orb-weaver,Uloborus diversus, based on immunostaining for the presynaptic component, synapsin, in whole-mounted spider synganglia. Aligned to this volume, we examined the expression patterns of neuronal populations representing many of the classical neurotransmitter and neuromodulators, as well as a subset of neuropeptides – detailing immunoreactivity in an unbiased fashion throughout the synganglion, revealing co-expression in known structures, as well as novel neuropils not evident in prior spider works.This optically-sliced, whole-mount atlas is the first of its kind for spiders, representing a substantive addition to knowledge of brain anatomy and neurotransmitter expression patterns for an orb-weaving species.
Maturation of human cardiac organoids enables complex disease modelling and drug discovery
Authors: Pocock Mark , Reid Janice D. , Robinson Harley R. , Charitakis Natalie , Krycer James R. , Foster Simon R. , Fitzsimmons Rebecca L. , Lor Mary , Tuano Natasha , Howden Sara , Vlahos Katerina , Watt Kevin I. , Piers Adam , Voges Holly K. , Fortuna Patrick R.J. , Rae James , Parton Robert G. , Konstantinov Igor E. , Weintraub Robert G. , Elliott David , Ramialison Mirana , Porrello Enzo R. , Mills Richard J. , Hudson James E. 
Published: September 2024

SummaryCardiac maturation is an important developmental phase culminating in profound biological and functional changes to adapt to the high demand environment after birth1,2. Maturation of human pluripotent stem cell-derived human cardiac organoids (hCO) to more closely resemble human heart tissue is critical for understanding disease pathology. Herein, we profile human heart maturationin vivo3to identify key signalling pathways that drive maturation in hCOs4,5. Transient activation of both the 5’ AMP-activated kinase (AMPK) and estrogen-related receptor (ERR) promoted hCO maturation by mimicking the increased functional demands of post-natal development. hCOs cultured under these directed maturation (DM) conditions (DM-hCOs) display robust transcriptional maturation including increased expression of mature sarcomeric and oxidative phosphorylation genes resulting in enhanced metabolic capacity. DM-hCOs have functionally mature properties such as sarcoplasmic reticulum-dependent calcium handling, accurate responses to drug treatments perturbing the excitation-coupling process and ability to detect ectopy CASQ2 and RYR2 mutants. Importantly, DM- hCOs permit modelling of complex human disease processes such as desmoplakin (DSP) cardiomyopathy, which is driven by multiple cell types. Subsequently, we deploy DM-hCOs to demonstrate that bromodomain extra-terminal inhibitor INCB054329 rescues theDSPphenotype. Together, this study demonstrates that recapitulatingin vivodevelopment promotes advanced maturation enabling disease modelling and the identification of a therapeutic strategy forDSP-cardiomyopathy.
Inter- and intra-tumor heterogeneous immune presentation in primary uterine carcinosarcoma determined by digital spatial profiling
Authors: Li Ying-Xuan , Lin Wei-Chou , Chen Ko-Chen , Chang Wen-Chun , Wu Chin-Jui , Wei Lin-Hung , Huang Ruby Yun-Ju , Sheu Bor-Ching 
Published: September 2024

AbstractUterine carcinosarcoma (UCS) is a rare gynecologic cancer with unfavorable prognosis. Its biphasic histologic components are known to associated with outcomes. Dissecting the tumor heterogeneity within UCS is crucial to discover molecular biomarkers for patient stratification. The aim of this study was to utilize spatial profiling technology to analyze immune presentation in different histological components within UCS tumors. The study included 23 UCS patients whose tumor sections were subjected to nanoString GeoMx Digital Spatial Profiling (DSP) to profile 30 immune-related proteins in 491 segments. We identified distinct cluster-labeled subtypes showing varied immune marker expressions. The immune presentations within the carcinoma and sarcoma components showed significant differences. Markers indicating M2 macrophages (CD45+CD163+) and epithelial-mesenchymal transition (EMT) (SMA, fibronectin) were highly expressed in the sarcoma components. The immune presentation subtypes within each histological component also differed between patients with recurrence in 5 years and without recurrence over 5 years. The cluster-labeled subtype with high Neutrophil/PMN-MDSC marker expression (CD66b) was associated with longer survival, whereas the subtype with high NK cell marker expressions (CD56) was linked to poor prognosis. Our result suggested that immune features within the carcinoma component of UCS tumors would determine patient outcomes and should be considered as a strategy for patient stratification.
The effect of unilateral hand muscle contraction on frontal alpha asymmetry and inhibitory control in intrinsic reward contexts, a randomized controlled trial
Authors: Akil Atakan M. , Cserjési Renáta , Nagy Tamás , Demetrovics Zsolt , Logemann H. N. Alexander 
Published: September 2024

ABSTRACTChallenged inhibitory control has been implicated in various disorders, including addiction. Previous research suggests that asymmetry of frontal brain activity, indexed by frontal alpha asymmetry (FAA), is associated with inhibitory control and could be a target for neuromodulatory intervention. Some evidence suggests that unilateral muscle contraction (UMC) can modulate FAA; however, experimental evidence is scarce. We conducted a randomized controlled trial, with 65 participants (Mage= 26.6; SD = 7.4), 37 of whom were females. We collected EEG data to calculate FAA and assessed inhibitory performance using the Stop Signal Task (SST) in neutral and intrinsic reward (palatable food) conditions, both before and after a unilateral left-hand muscle contraction task aimed at enhancing right relative to left frontal activity. We found a significant main effect of group on FAA. Specifically, UMC group was associated with higher right relative to left frontal activity, associated with resting state inhibitory activity. Event-related potential analyses revealed a significant dissociation between the stop N2 and stop P3 components as a function of time. More specifically, as time progressed, the stop N2 was enhanced, while the stop P3 was reduced. These results did not lead to observable changes in the behavioral index of stopping. In conclusion, UMC did not affect any behavioral and brain activity indices. There is some indication of a potential effect on FAA. However, this effect could reflect coincidental differences in trait FAA. Our findings provide new insights into the temporal dynamics of brain activity indices of inhibitory control.
scDrugAtlas: an integrative single-cell drug response atlas for unraveling tumor heterogeneity in therapeutic efficacy
Authors: Huang Wei , Ren Xinda , Bai Yinpu , Liu Hui 
Published: September 2024

AbstractTumor heterogeneity often leads to substantial differences in responses to same drug treatment. The presence of pre-existing or acquired drug-resistant cell sub-populations within a tumor survive and proliferate, ultimately resulting in tumor relapse and metastasis. The drug resistance is the leading cause of failure in clinical tumor therapy. Therefore, accurate identification of drug-resistant tumor cell subpopulations could greatly facilitate the precision medicine and novel drug development. However, the scarcity of single-cell drug response data significantly hinders the exploration of tumor cell resistance mechanisms and the development of computational predictive methods. In this paper, we propose scDrugAtlas, a comprehensive database devoted to integrating the drug response data at single-cell level. We manually compiled more than 100 datasets containing single-cell drug responses from various public resources. The current version comprises large-scale single-cell transcriptional profiles and drug response labels from more than 1,000 samples (cell line, mouse, PDX models, patients and bacterium), across 66 unique drugs and 13 major cancer types. Particularly, we assigned a confidence level to each response label based on the tissue source (primary or relapse/metastasis), drug exposure time and drug-induced cell phenotype. We believe scDrugAtlas could greatly facilitate the Bioinformatics community for developing computational models and biologists for identifying drug-resistant tumor cells and underlying molecular mechanism. The scDrugAtlas database is available at:http://drug.hliulab.tech/scDrugAtlas/.
FGFR2 promotes resistance to ALK tyrosine kinase inhibitors and its inhibition acts synergistically with lorlatinib in the treatment of ALK-expressing neuroblastoma
Authors: Pucci Perla , Barrett Charlotte , Trigg Ricky , Matthews Jamie D. , Borenäs Marcus , Schlederer Michaela , Jahangiri Leila , Hare Lucy , Steel Christopher , James Emily , Prokoph Nina , Kenner Lukas , Palmer Ruth , Hallberg Bengt , Burke G. A. Amos , Turner Suzanne D. 
Published: September 2024

ABSTRACTAnaplastic Lymphoma Kinase inhibitors (ALK TKIs) are approved for the treatment of ALK-positive non-small cell lung cancer (NSCLC) and are in clinical trial for ALK-aberrant high-risk neuroblastoma (NB) patients, particularly loratinib. However, resistance to ALK inhibitors can occur in patients, via the activation of bypass-signalling pathways, and there is a need to identify these mechanisms as well as drugs that inhibit them to design therapeutic approaches that prevent resistance, and to treat ALK TKI relapsed/refractory disease. Using genome-wide CRISPR-Cas9 overexpression screens, we identified and validatedFGFR2as a desensitizer to lorlatinib in aberrant ALK-expressing high-risk NB. FGFR2 and FGFR2-associated pathways are up-regulated in lorlatinib-resistant NB cells. Moreover, high-throughput screens using a library of 1,430 FDA approved drugs identified kinase inhibitors including those targeting FGFR2 as efficacious in reducing the survival of lorlatinib resistant NB cells. Hence, the FGFR pathway was investigated as a therapeutic target applying the pan-FGFR inhibitor erdafitinib or the multi-kinase inhibitor ponatinib, resulting in reduced survival of lorlatinib-resitant cells in comparison to their lorlatinib-sensitive counterparts. Moreover, both FGFR inhibitors act synergistically with lorlatinibin vitroandin vivo, using patient-derived xenografts (PDXs) and genetically engineered models (GEMM) of ALK-expressing NB.FGFR2mRNA expression also correlate with a poorer prognosis for NB patients, regardless of sub-type, suggesting that a broader range of patients may benefit from FGFR inhibitors. Overall, our data suggests that FGFR2 potentially plays roles in lorlatinib resistance in NB and that combined pharmacological inhibition of ALK and FGFR constitutes a therapeutic approach to treat high-risk NB.
Evaluating noise correction approaches for non-invasive electrophysiology of the human spinal cord
Authors: Bailey Emma , Nierula Birgit , Stephani Tilman , Maess Burkhard , Nikulin Vadim , Eippert Falk 
Published: September 2024

AbstractThe spinal cord is a vital component of the central nervous system for the processing of sensorimotor information transmitted between the body and the brain. Electrospinography (ESG) is the most accessible non-invasive technique for recording spinal signals in humans, but the vast and detrimental impact of physiological noise (mostly of cardiac nature) has prevented widespread adoption. Here, we aim to address this issue by examining various denoising algorithms for cardiac artefact reduction – including principal component analysis-based techniques (PCA), independent component analysis-based approaches (ICA) and signal space projection (SSP). We observed that in situations where large numbers of spinal electrodes are used, SSP offers the best results in terms of balancing the removal of harmful noise and preserving neural information of interest. In cases where only a small number of electrodes are available, an approach based on PCA is deemed helpful. Approaches based on ICA were found to be unsuitable for cardiac artefact removal in ESG, due to a suboptimal balance of artefact removal and signal preservation. Finally, we also approached this issue from a signal-enhancement perspective and observed that in cases where extensive electrode arrays are used in the context of task-based designs, a spatial filtering technique based on canonical correlation analysis (CCA) reveals clear evoked spinal potentials even with single-trial resolution. Taken together, there are several appropriate algorithms for physiological noise removal in ESG, rendering this an accessible and easy-to-use technique for non-invasive assessments of human spinal cord function.
Trained deep neural network models of the ventral visual pathway encode numerosity with robustness to object and scene identity
Authors: Chapalain Thomas , Thirion Bertrand , Eger Evelyn 
Published: September 2024

Abstract“Number sense”, the ability to quickly estimate quantities of objects in a visual scene, is present in humans and many other animals, and has recently been demonstrated in biologically inspired vision models, even before training. However, real-world number perception requires abstraction from the properties of individual objects and their contexts, in contrast to the simplified dot patterns used in previous studies. Using novel, synthetically generated photorealistic stimuli, we discovered that deep convolutional neural networks optimized for object recognition can encode numerical information across varying object and scene identities in their distributed activity patterns. In contrast, untrained networks failed to discriminate numbers, and appeared to encode low-level visual summary statistics of scenes rather than the number of discrete objects per se. These results caution against using untrained networks to model early numerical abilities and highlight the need to use more complex stimuli to understand the mechanisms behind the brain’s visual number sense.
Immune Cell Influence on Diffuse Large B-Cell Lymphoma: A Mendelian Randomization Analysis
Authors: He Honghua , Zhong Jihong , Li Qinghua , Deng Chen , Yuan Xin , Zhang Kaixiang , Nie Lirong , Cai Nali 
Published: September 2024

AbstractObjectiveTo elucidate the causal relationship between immune cells and diffuse large B-cell lymphoma (DLBCL), we conducted a Mendelian randomization analysis.MethodsMendelian randomization (MR) leverages genetic variants as instruments to infer causal effects from observational data. Here, we performed a two-sample MR analysis to assess the causal impact of 731 immune cell types on DLBCL. We employed various MR techniques, including the weighted median estimator (WME) and inverse variance weighting (IVW), and conducted sensitivity analyses to ensure result robustness. Additionally, reverse MR analysis was performed to explore the potential causal relationship between DLBCL and immune cells.ResultsWe identified seventeen immune features with causal links to DLBCL, categorized across various cellular groups: four in B cells, two in T cell maturation stages, six in Tregs, four in the TBNK group, and one in dendritic cells (DCs). Sensitivity analyses confirmed the absence of heterogeneity, horizontal pleiotropy, and bias in our findings. Reverse causal analysis revealed a causal association between DLBCL and one of the seventeen immune cell types identified.ConclusionsOur MR analysis of seventeen immune cell types uncovers the complex interactions between the immune system and DLBCL, providing crucial insights into the tumor microenvironment and potential avenues for targeted immunotherapy.
Structured and unstructured reactivations during REM sleep are modulated by novel experiences
Authors: Choi Jisoo , Carmichael James , Williams Sylvain , Etter Guillaume 
Published: September 2024

AbstractMammalian sleep is composed of two distinct phases characterized by unique neural activity patterns: rapid eye movement (REM) and non-REM (nREM) sleep. While both phases are essential for memory consolidation, neural replay of awake experience as a candidate mechanism for memory consolidation has only been shown for nREM sleep and it remains unclear whether awake experiences are reactivated during REM sleep. Here, we evaluated whether awake experiences are reactivated by hippocampal CA1 pyramidal neurons during REM sleep using a combination of approaches including Bayesian decoding, sequence factorization, and co-activation analysis. We confirmed that representations of awake exploration are recapitulated during subsequent REM episodes with varying levels of temporal structure. We also found that temporally organized sequences were replayed with a higher frequency during REM sleep following a novel experience. Finally, we find internalized structure in CA1 activity prior to novel task exposure that is expressed in subsequent behaviour. Altogether, these results suggest that while hippocampal ensembles appear as a result of structural priors, salient experiences refine temporal sequences during subsequent REM sleep, suggesting a unique role for REM sleep in salient-experience consolidation.
Identifying Functional Homologues in Human and Marmoset Brain Networks via Movie-Driven Ultra-High Field fMRI
Authors: Zanini A. , Dureux A. , Menon R.S. , Everling S. 
Published: September 2024

AbstractNumerous task-based functional magnetic resonance imaging (fMRI) studies have demonstrated that complex neural functions such as language processing, action observation, face recognition, and motor coordination are governed by widespread, intricate networks that span both cortical and subcortical areas. Nonhuman primate models are indispensable for advancing our understanding of the evolution of these networks and provide unique opportunities for experimental interventions that are not feasible in humans. In this study, we utilized movie-driven fMRI (md-fMRI) to investigate and delineate homologous functional networks in the common marmoset (Callithrix jacchus). Both marmosets and human subjects watched the same movie which incorporated a variety of visual and auditory stimuli. This method enabled the identification of potential homologues of large-scale functional networks involved in visual, auditory, cognitive, motor, and limbic functions in marmosets, offering new insights into the shared neurofunctional architecture across species.
Engineering the auxin-inducible degron system for tunablein vivocontrol of organismal physiology
Authors: Vicencio Jeremy , Chihara Daisuke , Eder Matthias , Ahringer Julie , Stroustrup Nicholas 
Published: September 2024

ABSTRACTThe physiological mechanisms governing health and disease exhibit complex interactions between multiple genes and gene products. To study the dynamics of living systems, researchers need experimental methods capable of producing calibrated, quantitative perturbationsin vivo— perturbations that cannot be obtained using classical genetics, RNAi interference, or small molecule drugs. Recently, an auxin-inducible degron (AID) system has been developed to allow targeted degradation of proteins using small-molecule activators, providing spatiotemporal control of protein abundance. However, a better understanding of the biochemical activities of AID system components in their physiological context is needed to design quantitative interventions.Here, we apply engineering approaches to characterize and understand the performance of several AID technologies and then improve this performance in the multicellular animalCaenorhabditis elegans. We 1) develop new technologies that allow for a careful calibration of AID activity for specific purposes; 2) develop new TIR1 enzyme constructs with improved performance over existing constructs; 3) develop an approach to simultaneously and independently degrade target proteins in distinct tissues; and finally, 4) develop an approach for pan-organismal protein degradation by re-engineering the TIR1 enzyme. Taken together, these advances enable new quantitative experimental approaches to study the cellular and systems dynamics of animals.
Paradise fish (Macropodus opercularis) as a novel translational model for emotional and cognitive function
Authors: Varga Zoltán K. , Pejtsik Diána , Csorvás Tímea , Mikics Éva , Miklósi Ádám , Varga Máté 
Published: September 2024

ABSTRACTZebrafish have revolutionised physiological screening in vertebrates, but the interpretation of individual-based behavioural assays is burdened by the strong sociality of this species. We propose the use of a solitaire fish species, the paradise fish to keep the advantages and compensate for the limitations of the zebrafish model. We compared juvenile paradise fish and zebrafish in social and non-social exploratory tasks, anxiety tests and in a working memory assay to assess their performance in these individual-based models. We found that in contrast to zebrafish, paradise fish did not show social approach in the U-shape sociability test, their novelty exploration was not biased by the presence of a conspecific in the slalom test, and was not impaired by social isolation in the showjump or in the swimming plus-maze (SPM) anxiety tests. While social circumstances did not affect the anxiety of paradise fish, it was sensitive to the anxiolytic drug buspirone. Intra- and interest repeatability measures of the anxiety tests revealed that paradise fish express more consistent exploratory and defensive behaviours regarding time and context compared to zebrafish. Behavioural consistency in paradise fish was also supported by arm alternation as a predominant choice of exploration in the y-maze task. In summary, our results indicate that the behaviour of paradise fish is less biased by social cues and is more effective and repeatable in individual-based assays than zebrafish behaviour. We hypothesise that the two phenomena are connected and novelty exploration, anxiety and working memory can be more reliably measured and are translatable in a solitaire species.