bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale Effects of Excitatory-Inhibitory Homeostasis in Lesioned Cortical Networks: A Computational Study
Authors: Páscoa dos Santos Francisco , Vohryzek Jakub , Verschure Paul F.M.J. 
Published: November 2022

AbstractStroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesion-dependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic pain. In summary, our results show that the effects of E-I homeostasis extend beyond local E-I balance, driving the restoration of global properties of FC, and relating to post-stroke symptomatology. Therefore, we suggest the framework of E-I homeostasis as a relevant theoretical foundation for the study of stroke recovery and for understanding the emergence of meaningful features of FC from local dynamics.
MOF-mediated Histone H4 Lysine 16 Acetylation Governs Mitochondrial and Ciliary Functions By Controlling Gene Promoters
Authors: Wang Dongmei , Li Haimin , Chandel Navdeep S , Dou Yali , Yi Rui 
Published: November 2022

AbstractHistone H4 lysine 16 acetylation (H4K16ac), governed by the histone acetyltransferase (HAT) MOF, orchestrates critical functions in gene expression regulation and chromatin interaction. However, how does MOF and H4K16ac control cellular function and regulate mammalian tissue development remains unclear. Furthermore, whether the function of MOF is mediated by MSL or NSL, two distinct MOF-containing HAT complexes, have not been determined during mammalian development. Here we show that conditional deletion ofMofbut notKansl1, an essential component of the NSL complex, causes severe defects during murine skin development. In the absence ofMofand H4K16ac, basal epithelial progenitors of mammalian skin fail to establish the basement membrane and cell polarity, causing the failure of self-renewal. Furthermore, epidermal differentiation and hair growth are severely compromised, leading to barrier defects and perinatal lethality. Single-cell and bulk RNA-seq, in combination with MOF ChIP-seq, reveal that MOF regulated genes are highly enriched in mitochondria and cilia. Mechanistically, MOF coordinates with RFX2 transcription factor, which preferentially binds to gene promoters, to regulate ciliary and mitochondrial genes. Importantly, genetic deletion ofUqcrq, a nuclear-encoded, essential subunit for electron transport chain (ETC) Complex III, recapitulates the defects of epidermal differentiation and hair follicle growth observed in MOF cKO. Together, this study reveals the requirement of MOF-mediated epigenetic mechanism for mitochondria and cilia, and demonstrates the important function of the MOF/ETC axis for mammalian skin development.
Multiplexed and scalable cellular phenotyping toward the standardized three-dimensional human neuroanatomy
Authors: Murakami Tatsuya C. , Heintz Nathaniel 
Published: November 2022

SUMMARYThe advent of three-dimensional histological methods has advanced studies of cellular-resolution anatomy of the brain. The use of whole-mount staining and tissue clearing has advanced systems-level identification of cells underlying brain functions in mouse models. However, application of these methods to studies of human brains has been difficult due to their structural variability and the lack of standardized quantitative metrics. Here we report a rapid and scalable staining/imaging technique, termed mFISH3D, that enables single-cell-resolution imaging of mRNAs of more than ten genes in a large mammalian brain. To apply mFISH3D to postmortem human cerebral cortex, we have reconstructed morphogenic tracks of cortical growth, and used the tracks to provide a framework for quantitative assessment of cytoarchitecture. The workflow enabled the objective quantification of biological heterogeneity among cortical regions. We propose these techniques for standardization of 3D histology of the human cortex to provide reproducible measurements of cell-type-specific neuroanatomy.
Interactions between circuit architecture and plasticity in a closed-loop system
Authors: Payne Hannah L. , Raymond Jennifer L. , Goldman Mark S. 
Published: November 2022

AbstractDetermining the sites of plasticity underlying changes in neural activity and behavior is critical for understanding mechanisms of learning. Identifying such sites from neural recording data can be challenging due to feedback pathways that impede reasoning about cause and effect. We studied interactions between feedback, neural activity, and plasticity in the context of a closed-loop motor learning task for which there is disagreement about the loci and directions of plasticity. We constructed a set of models that differed in the strength of their recurrent feedback. Despite these differences, each model successfully fit a large set of neural and behavioral data. However, the patterns of plasticity predicted by the models fundamentally differed, with the sign of plasticity at a key site changing from depression to potentiation as feedback strength increased. Guided by our analysis, we suggest how such models can be experimentally disambiguated. Our results address a long-standing debate regarding cerebellum-dependent motor learning and demonstrate how learning-related changes in neural activity can appear to contradict the sign of the underlying plasticity when feedback is present.
Consensus Label Propagation with Graph Convolutional Networks for Single-Cell RNA Sequencing Cell Type Annotation
Authors: Lewinsohn Daniel P , Vigh-Conrad Katinka A , Conrad Donald F , Scott Cory B 
Published: November 2022

AbstractMotivationSingle-cell RNA sequencing (scRNA-seq) data, annotated by cell type, is useful in a variety of downstream biological applications, such as profiling gene expression at the single-cell level. However, manually assigning these annotations with known marker genes is both time-consuming and subjective.ResultsWe present a Graph Convolutional Network (GCN) based approach to automate the annotation process. Our process builds upon existing labeling approaches, using state-of-the-art tools to find cells with highly confident label assignments through consensus and spreading these confident labels with a semi-supervised GCN. Using simulated data and two scRNA-seq data sets from different tissues, we show that our method improves accuracy over a simple consensus algorithm and the average of the underlying tools. We also compare our method to a non-parametric neighbor majority approach, showing comparable results. We then demonstrate that our GCN method allows for feature interpretation, identifying important genes for cell type classification. We present our completed pipeline, written in PyTorch, as an end-to-end tool for automating and interpreting the classification of scRNA-seq data.AvailabilityOur code for conducting the experiments in this paper and using our model is available athttps://github.com/lewinsohndp/scSHARPContactd_lewinsohn@coloradocollege.eduSupplementary informationSupplementary data are available atJournal Nameonline.
Caught in the Act: targeted mutagenesis of the herpesvirus fusogen central helix captures transition states
Authors: Zhou Momei , Vollmer Benjamin , Machala Emily , Chen Muyuan , Grünewald Kay , Arvin Ann M. , Chiu Wah , Oliver Stefan L. 
Published: November 2022

AbstractHerpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Structure-function studies of the VZV gB DIII central helix were performed targeting residues526EHV528. Critically, a H527P mutation captured gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] were identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.
Progressive neural engagement within the IFG-pMTG circuit as gesture and speech entropy and MI advances
Authors: Zhao Wanying , Li Zhouyi , Li Xiang , Du Yi 
Published: November 2022

AbstractSemantic representation emerges from distributed multisensory modalities, yet a comprehensive understanding of the functional changing pattern within convergence zones or hubs integrating multisensory semantic information remains elusive. In this study, employing information-theoretic metrics, we quantified gesture and speech information, alongside their interaction, utilizing entropy and mutual information (MI). Neural activities were assessed via interruption effects induced by High-Definition transcranial direct current stimulation (HD-tDCS). Additionally, chronometric double-pulse transcranial magnetic stimulation (TMS) and high-temporal event-related potentials were utilized to decipher dynamic neural changes resulting from various information contributors. Results showed gradual inhibition of both inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) as degree of gesture-speech integration, indexed by MI, increased. Moreover, a time-sensitive and staged progression of neural engagement was observed, evidenced by distinct correlations between neural activity patterns and entropy measures of speech and gesture, as well as MI, across early sensory and lexico-semantic processing stages. These findings illuminate the gradual nature of neural activity during multisensory gesture-speech semantic processing, shaped by dynamic gesture constraints and speech encoding, thereby offering insights into the neural mechanisms underlying multisensory language processing.
Monitoring mouse brain perfusion with hybrid magnetic resonance optoacoustic tomography
Authors: Ren Wuwei , Deán-Ben Xosé Luís , Skachokova Zhiva , Augath Mark-Aurel , Ni Ruiqing , Chen Zhenyue , Razansky Daniel 
Published: November 2022

AbstractProgress in brain research critically depends on the development of next-generation multi-modal imaging tools that are capable of capturing transient functional events and multiplexed contrasts noninvasively and concurrently. A number of outstanding questions, such as those pertaining to the link between blood-oxygen-level-dependent (BOLD) signaling, oxygen saturation and underlying neural activity, could potentially be addressed by truly integrating several complementary neuroimaging readouts into one hybrid system, thus enabling a holistic view of dynamic eventsin vivo. Here we developed a hybrid magnetic resonance and optoacoustic tomography (MROT) system for murine brain imaging by incorporating an MR-compatible spherical matrix array transducer and fiberbased light illumination into a 9.4T small animal scanner, whilst further designing an optimized radiofrequency coil for whole-brain interrogation. The utility of the system is demonstrated by acquiring complementary angiographic and soft tissue anatomical contrast along with simultaneous dual-modality visualization of contrast agent dynamicsin vivo.
Natural genetic variation in the pheromone production ofC. elegans
Authors: Lee Daehan , Fox Bennett W. , Palomino Diana C. F. , Panda Oishika , Tenjo Francisco J. , Koury Emily J. , Evans Kathryn S. , Stevens Lewis , Rodrigues Pedro R. , Kolodziej Aiden R. , Schroeder Frank C. , Andersen Erik C. 
Published: November 2022

AbstractFrom bacterial quorum sensing to human language, communication is essential for social interactions. Nematodes produce and sense pheromones to communicate among individuals and respond to environmental changes. These signals are encoded by different types and mixtures of ascarosides, whose modular structures further enhance the diversity of this nematode pheromone language. Interspecific and intraspecific differences in this ascaroside pheromone language have been described previously, but the genetic basis and molecular mechanisms underlying the variation remain largely unknown. Here, we analyzed natural variation in the production of 44 ascarosides across 95 wildCaenorhabditis elegansstrains using high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS). By cross-analyzing genomes andexo-metabolomes of wild strains, we discovered quantitative trait loci (QTL) that underlie the natural differences in pheromone bouquet composition. Fine mapping of the QTL further uncovered associations between mitochondrial metabolism and pheromone production. Our findings demonstrate how natural genetic variation in core metabolic pathways can affect the production of social signals.
Prediction and diagnosis of chronic kidney disease development and progression using machine-learning: protocol for a systematic review and meta-analysis of reporting standards and model performance
Authors: Chen Fangyue , Kantagowit Piyawat , Nopsopon Tanawin , Chuklin Arisa , Pongpirul Krit 
Published: November 2022

AbstractChronic Kidney disease (CKD) is an important yet under-recognized contributor to morbidity and mortality globally. Machine-learning (ML) based decision support tools have been developed across many aspects of CKD care. Notably, algorithms developed in the prediction and diagnosis of CKD development and progression may help to facilitate early disease prevention, assist with early planning of renal replacement therapy, and offer potential clinical and economic benefits to patients and health systems. Clinical implementation can be affected by the uncertainty surrounding the methodological rigor and performance of ML-based models. This systematic review aims to evaluate the application of prognostic and diagnostic ML tools in CKD development and progression.The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. The systematic review protocol for CKD prediction and diagnosis have been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022356704, CRD42022372378). A systematic search will be undertaken of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the IEEE Xplore digital library. Studies in which ML has been applied to predict and diagnose CKD development and progression will be included. The primary outcome will be the comparison of the performance of ML-based models with non-ML-based models. Secondary analysis will consist of model use cases, model construct, and model reporting quality.This systematic review will offer valuable insight into the performance and reporting quality of ML-based models in CKD diagnosis and prediction. This will inform clinicians and technical specialists of the current development of ML in CKD care, as well as direct future model development and standardization.
Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community
Authors: Weiss Anna S. , Niedermeier Lisa S. , von Strempel Alexandra , Burrichter Anna G. , Ring Diana , Meng Chen , Kleigrewe Karin , Lincetto Chiara , Hübner Johannes , Stecher Bärbel 
Published: November 2022

AbstractMicrobe-microbe interactions are critical for gut microbiome function. A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Here, we aimed to determine members taking on a keystone role in shaping community ecology of a widely used synthetic bacterial community (OMM12). Using single-species dropout communities and metabolomic profiling, we identifiedBacteroides caecimurisI48,Blautia coccoidesYL58 andEnterococcus faecalisKB1 as major drivers ofin vitrocommunity assembly and elucidated underlying mechanisms of these keystone functions. Importantly, keystone species and bacterial strain relationships were found to strongly vary across different nutritional conditions, depending on the strains’ potential to modify the corresponding environment. Further, gnotobiotic mice transplanted with communities lackingB. caecimurisI48 andB. coccoidesYL58 exhibited morphological anomalies and altered intestinal metabolomic profiles, exposing physiologically relevant functions of these keystone community members. In summary, the presented study experimentally confirms the strong interdependency between bacterial community ecology and the biotic and abiotic environment, underlining the context-dependency and conditionality of bacterial interaction networks.
A simplified, amplicon-based method for whole genome sequencing of human respiratory syncytial viruses
Authors: Dong Xiaomin , Deng Yi-Mo , Aziz Ammar , Whitney Paul , Clark Julia , Harris Patrick , Bautista Catherine , Costa Anna Maria , Waller Gregory , Daley Andrew J , Wieringa Megan , Korman Tony , Barr Ian G. 
Published: November 2022

AbstractHuman Respiratory Syncytial Virus (RSV) infections pose a significant risk to human health worldwide, especially for young children. Whole genome sequencing (WGS) provides a useful tool for global surveillance to better understand the evolution and epidemiology of RSV and provide essential information that may impact on antibody treatments, antiviral drug sensitivity and vaccine effectiveness. Here we report the development of a rapid and simplified amplicon-based one-step multiplex reverse-transcription polymerase chain reaction (mRT-PCR) for WGS of both human RSV-A and RSV-B viruses. The method requires only two reactions for each sample, which significantly reduces the cost and time compared to other commonly used RSV WGS methods. In silico analysis and laboratory testing revealed that the primers used in the new method covered most of the currently circulating RSV-A and RSV-B. Amplicons generated were suitable for both Illumina and Oxford Nanopore Technologies (ONT) NGS platforms. This new method was tested on 200 clinical samples collected in Australia in 2020 and 2021 with RSV Ct values between 10 and 32. A success rate of 88% with a full coverage for the genome of 99 RSV-A and 77 RSV-B was achieved. This assay is simple to set up, robust, easily scalable in sample preparation and relatively inexpensive, and as such, provides a valuable addition to existing NGS RSV WGS methods.
MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells
Authors: Röring Rutger J. , Debisarun Priya A. , Botey-Bataller Javier , Suen Tsz Kin , Bulut Özlem , Kilic Gizem , Koeken Valerie A. C. M. , Sarlea Andrei , Bahrar Harsh , Dijkstra Helga , Lemmers Heidi , Gössling Katharina L. , Rüchel Nadine , Ostermann Philipp N. , Müller Lisa , Schaal Heiner , Adams Ortwin , Borkhardt Arndt , Ariyurek Yavuz , de Meijer Emile J. , Kloet Susan , ten Oever Jaap , Placek Katarzyna , Li Yang , Netea Mihai G. 
Published: November 2022

AbstractThe measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in γδ T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination.One-sentence summaryMMR vaccination induces cellular and metabolic reprogramming in γδ T cells towards a more active phenotype.
Reconstruction of Three-Dimensional Trajectories of Honeybees Flying in High-Density Aerial Environments
Authors: Mahadeeswara Mandiyam Yadav , Srinivasan Mandyam V 
Published: November 2022

AbstractSo far, relatively few studies have investigated the flight of insects moving in experimental conditions approximating natural scenes. This is mainly because of the technical difficulties involved in detecting and tracking individual insects in three dimensions in outdoor scenarios, as well as matching views of corresponding insects in stereo images for trajectory reconstruction (the so-called ‘Correspondence Problem’). In this study, we describe the methods we have developed to track and unambiguously reconstruct the trajectories and body orientations of a large number of bees flying in close proximity in a ‘bee cloud’, using just two high-speed video cameras configured as a stereo pair in a semi-outdoor setting. Using these methods, two separate bee clouds were filmed and the data were analysed to reconstruct the three-dimensional trajectories, including the head and tail positions, of a total of 382 bees. This dataset should enable future analysis of the movement characteristics of bees flying in a dense environment, as well as uncover potential strategies for mid-air collision avoidance.