bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)
Authors: Shariff Muhammed , Dobariya Aksharkumar , Albaghdadi Obada , Awkal Jacob , Moussa Hadi , Reyes Gabriel , Syed Mansur , Hart Robert , Longfellow Cameron , Douglass Debra , El Ahmadieh Tarek Y. , Good Levi B. , Jakkamsetti Vikram , Kathote Gauri , Angulo Gus , Ma Qian , Brown Ronnie , Dunbar Misha , Shelton John M. , Evers Bret M. , Patnaik Sourav , Hoffmann Ulrike , Hackmann Amy E. , Mickey Bruce , Peltz Matthias , Jessen Michael E. , Pascual Juan M. 
Published: May 2023

AbstractSelective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even when preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.
Improving the prediction of protein stability changes upon mutations by geometric learning and a pre-training strategy
Authors: Xu Yunxin , Liu Di , Gong Haipeng 
Published: May 2023

AbstractAccurate prediction of the fitness and stability of a protein upon mutations is of high importance in protein engineering and design. Despite the rapid development of deep learning techniques and accumulation of experimental data, the multi-labeled nature of fitness data hinders the training of robust deep-learning-based models for the fitness and stability prediction tasks. Here, we propose three geometric-learning-based models, GeoFitness, GeoDDG and GeoDTm, for the prediction of the fitness score, ΔΔGand ΔTmof a protein upon mutations, respectively. In the optimization of GeoFitness, we designed a novel loss function to allow supervised training of a unified model using the large amount of multi-labeled fitness data in the deep mutational scanning (DMS) database. By this means, GeoFitness efficiently learns the general functional effects of protein mutations and achieves better performance over the other state-of-the-art methods. To further improve the downstream tasks of ΔΔG/ΔTmprediction, we re-utilized the encoder of GeoFitness as a pre-trained module in GeoDDG and GeoDTm to overcome the challenge of lack of sufficient amount of specifically labeled data. This pre-training strategy in combination with data expansion remarkably improves model performance and generalizability. When evaluated on the benchmark test sets (S669 for ΔΔGprediction and a newly collected set S571 for ΔTmprediction), GeoDDG and GeoDTm outperform the other state-of-the-art methods by at least 30% and 70%, respectively, in terms of the Spearman correlation coefficient between predicted and experimental values. An online server for the suite of these three predictors, GeoStab-suite, is available athttp://structpred.life.tsinghua.edu.cn/server_geostab.html.
Genome-wide profiling reveals a dual role for histone H2A monoubiquitylation at Polycomb-repressed and enhancer chromatin
Authors: MacGillivray Kailynn , Fusca Daniel , Tan Luomeng , Aram Reta , Saltzman Arneet L. 
Published: May 2023

AbstractHistone modifications are an integral component of eukaryotic genome regulation. Polycomb Repressive Complex 1 (PRC1) is responsible for depositing histone H2A lysine 119 monoubiquitylation (H2AK119ub) and can work cooperatively with PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) to maintain gene repression. However, H3K27me3-independent functions and roles in gene activation have also been described for PRC1. Thus, the extent to which Polycomb complexes and their corresponding histone modifications function together or independently and the conservation of these roles in different organisms is unclear. UsingC. elegansas a model, we investigated the relationship between H2AK119ub and H3K27me3. Here we show that the majority of H2AK119ub and H3K27me3 enrichment across the genome in embryos is distinct, and that the bulk levels of these modifications are regulated independently. We identify many genes related to nervous system development and functionality that have H2AK119ub-enriched promoters and are misregulated in H2AK119ub-deficient mutants, including a subset of genes that are normally H3K27me3-repressed. Surprisingly, we also find an enrichment of H2AK119ub at enhancers, including enhancers proximal to genes which are both up-regulated and down-regulated following the loss of this histone modification. Together, our results indicate a dual role for H2AK119ub in the regulation of both H3K27me3-repressed and enhancer chromatin states.
Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis
Authors: Wang Lianlei , Liu Zhaoyang , Zhao Sen , Xu Kexin , Aceves Valeria , Qiu Cheng , Troutwine Benjamin , Liu Lian , Ma Samuel , Niu Yuchen , Wang Shengru , Yuan Suomao , Li Xiaoxin , Zhao Lina , Liu Xinyu , Wu Zhihong , Zhang Terry Jianguo , Gray Ryan S. , Wu Nan 
Published: May 2023

ABSTRACTSOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation ofSOX9is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of howSOX9variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants ofSOX9identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain ofSOX9. Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated aSox9hypomorphic mutant mouse model bearing a microdeletion within the TAM domain (Sox9Asp272del). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. HomozygousSox9Asp272delmice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs inSox9Asp272delmutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant ofSOX9within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.
Joint cell type identification in spatial transcriptomics and single-cell RNA sequencing data
Authors: Geras Agnieszka , Domżał Kacper , Szczurek Ewa 
Published: May 2023

AbstractUnderstanding the intricate composition of tissues in complex living organisms is crucial for unraveling the mechanisms underlying health and disease. This study addresses the challenge of dissecting cell types within tissues by integrating information from two powerful experimental techniques: single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST). While scRNA-seq offers insights into transcriptional heterogeneity at the cellular level, ST provides spatial information within tissues. Current methods for cell-type annotation in scRNA-seq and mixture decomposition in ST data are often conducted independently, resulting in reduced statistical power and accuracy. To bridge this gap, we propose ST-Assign, a novel hierarchical Bayesian probabilistic model that jointly performs cell-type annotation in scRNA-seq data and cell-type mixture decomposition in ST data. ST-Assign accounts for shared variables such as gene expression profiles and leverages prior knowledge about marker genes, amplifying statistical strength and mitigating experimental noise. The model’s excellent performance is demonstrated on simulated and real mouse brain data, showcasing accurate cell-type mixture decomposition and cell-type assignment. In comparison to existing tools, ST-Assign demonstrates superior capabilities, particularly in the task of assigning cell types to individual cells. ST-Assign enables exploring the spatial composition of cell types and holds the potential for enhancing our comprehension of diverse biological systems.
Permeabilization status affects the relationship between basal metabolic rate and mitochondrial respiration in great tit blood cells
Authors: Thoral Elisa , García Díaz Carmen C. , Persson Elin , Chamkha Imen , Elmér Eskil , Ruuskanen Suvi , Nord Andreas 
Published: May 2023

AbstractAlthough mitochondrial respiration is believed to explain a substantial part of the variation in whole-animal basal (BMR) or resting metabolic rate (RMR), few studies have addressed the relationship between organismal and cellular metabolism and how this may vary in environments where individual demands for energy differ. We investigated the relationship between whole-individual metabolic rate, measured in temperatures ranging thermoneutrality to far below thermoneutrality, and mitochondrial respiration of intact or permeabilized blood cells in two separate studies on wild great tits (Parus majorL.). Our results show that, in permeabilized cells, there are significant positive relationships between BMR or RMR and several mitochondrial traits, including phosphorylating respiration rate through both complexes I and II (i.e., OXPHOS respiration). However, surprisingly, the LEAK respiration (i.e., basal respiration that mainly counteract for proton leakage) was not related to BMR or RMR. When measurements were performed using intact blood cells, BMR was positively related to ROUTINE respiration (i.e., mitochondrial respiration on endogenous substrates) in one of the two studies, but no other mitochondrial traits could explain variation in BMR or RMR in any thermal environment. These studies seem to show that the level of activation of mitochondrial metabolism as well as the permeabilization status of blood cells play a primary role on the extent to which blood metabolism might explain variations in the whole-individual metabolic rate.
Huge narwhal displacement following shipping of iron ore in the Canadian Arctic Archipelago
Authors: Witting Lars 
Published: May 2023

AbstractWith 100,000 narwhals inhabiting populations in the Canadian Arctic Archipelago, the Northwest Passage runs through the largest aggregation of narwhals in the world. I use a metapopulation analysis that covers eight of the narwhal populations in the area to estimate that about 25,000 narwhals have emigrated from Eclipse Sound to Admiralty Inlet since 2007, causing almost total population collapse in Eclipse Sound following shipping of iron ore through Milne Inlet and Eclipse Sound. It is estimated that up to about 30,000 narwhals may vanish in the long run, unless shipping is increasingly regulated, or narwhals adapt to the disturbance and reinhabits the abandoned areas. Reflecting only a local disturbance, these population effects warn against intense shipping in other fjords with narwhals, and against a potentially much larger impact from increased shipping through the Northwest Passage in the future.
Antibodies against SARS-CoV-2 control complement-induced inflammatory responses to SARS-CoV-2
Authors: Bermejo-Jambrina Marta , van der Donk Lieve E.H. , van Hamme John L. , Wilflingseder Doris , de Bree Godelieve , Prins Maria , de Jong Menno , Nieuwkerk Pythia , van Gils Marit J. , Kootstra Neeltje A. , Geijtenbeek Teunis B.H. 
Published: May 2023

AbstractDysregulated immune responses contribute to pathogenesis of COVID-19 leading to uncontrolled and exaggerated inflammation observed during severe COVID-19. However, it remains unclear how immunity to SARS-CoV-2 is induced and subsequently controlled. Notably, here we have uncovered an important role for complement in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonized SARS-CoV-2 via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently interacted with dendritic cells (DCs), inducing type I IFN and pro-inflammatory cytokine responses, which were inhibited by antibodies against the complement receptors (CR)3 and CR4. These data suggest that complement is important in inducing immunity via DCs in the acute phase against SARS-CoV-2. Strikingly, serum from COVID-19 patients as well as monoclonal antibodies against SARS-CoV-2 attenuated innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking the FcyRII, CD32, restored complement-induced immunity. These data strongly suggest that complement opsonization of SARS-CoV-2 is important for inducing innate and adaptive immunity to SARS-CoV-2. Subsequent induction of antibody responses is important to limit the immune responses and restore immune homeostasis. These data suggest that dysregulation in complement and FcyRII signalling might underlie mechanisms causing severe COVID-19.
Human plasma-like medium facilitates metabolic tracing and enables upregulation of immune signaling pathways in glioblastoma explants
Authors: Shami Mohamad El , Savani Milan R , Gattie Lauren C , Smith Bailey , Hicks William H , Rich Jeremy N , Richardson Timothy E , McBrayer Samuel K , Abdullah Kalil G 
Published: May 2023

AbstractPurposeMetabolism within the tumor microenvironment (TME) represents an increasing area of interest to understand glioma initiation and progression. Stable isotope tracing is a technique critical to the study of tumor metabolism. Cell culture models of this disease are not routinely cultured under physiologically relevant nutrient conditions and do not retain cellular heterogeneity present in the parental TME. Moreover, in vivo, stable isotope tracing in intracranial glioma xenografts, the gold standard for metabolic investigation, is time consuming and technically challenging. To provide insights into glioma metabolism in the presence of an intact TME, we performed stable isotope tracing analysis of patient-derived, heterocellular Surgically eXplanted Organoid (SXO) glioma models in human plasma-like medium (HPLM).MethodsGlioma SXOs were established and cultured in conventional media or transitioned to HPLM. We evaluated SXO cytoarchitecture and histology, then performed spatial transcriptomic profiling to identify cellular populations and differential gene expression patterns. We performed stable isotope tracing with15N2-glutamine to evaluate intracellular metabolite labeling patterns.ResultsGlioma SXOs cultured in HPLM retain cytoarchitecture and cellular constituents. Immune cells in HPLM-cultured SXOs demonstrated increased transcription of immune-related signatures, including innate immune, adaptive immune, and cytokine signaling programs.15N isotope enrichment from glutamine was observed in metabolites from diverse pathways, and labeling patterns were stable over time.ConclusionTo enable ex vivo, tractable investigations of whole tumor metabolism, we developed an approach to conduct stable isotope tracing in glioma SXOs cultured under physiologically relevant nutrient conditions. Under these conditions, SXOs maintained viability, composition, and metabolic activity while exhibiting increased immune-related transcriptional programs.
The Bergen Breakfast Scanning Club dataset: a deep brain imaging dataset
Authors: Wang Meng-Yun , Korbmacher Max , Eikeland Rune , Specht Karsten 
Published: May 2023

AbstractPopulational brain imaging methods based on group averages provide valuable insights into the general functions of the brain. However, they often overlook the inherent inter- and intra-subject variability, limiting our understanding of individual differences. To address this limitation, researchers have turned to big datasets and deep brain imaging datasets. Big datasets enable the exploration of inter-subject variations, while deep brain imaging datasets, involving repeated scanning of multiple subjects over time, offer detailed insights into intra-subject variability. Despite the availability of numerous big datasets, the number of deep brain imaging datasets remains limited. In this article, we present a deep brain imaging dataset derived from the Bergen Breakfast Scanning Club (BBSC) project. The dataset comprises data collected from three subjects who underwent repeated scanning over the course of approximately one year. Specifically, three types of data chunks were collected: behavioral data, functional brain data, and structural brain data. Functional brain images, encompassing magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI), along with their anatomical reference T1-weighted brain images, were collected twice a week during the data collection period. In total, 38, 40, and 25 sessions of functional data were acquired for subjects 1, 2, and 3, respectively. On the other hand, structural brain images, including T2-weighted brain images, diffusion-weighted images (DWI), and fluid-attenuated inversion recovery (FLAIR) images, were obtained once a month. A total of 10, 9, and 6 sessions were collected for subjects 1, 2, and 3, respectively.The primary objective of this article is to provide a comprehensive description of the data acquisition protocol employed in the BBSC project, as well as detailed insights into the preprocessing steps applied to the acquired data.
Comparison of eDNA, bulk-sample metabarcoding, and morphological approaches: A case study of riverine benthic macroinvertebrate communities
Authors: Doloiras-Laraño Arnelyn D. , Yaegashi Sakiko , Serrana Joeselle M. , Ishitani Naoto , Watanabe Kozo 
Published: May 2023

AbstractFreshwater biomonitoring is essential for aquatic biodiversity conservation. Advances in high-throughput sequencing allowed parallel sequencing of community samples containing DNA from environmental samples, i.e., metabarcoding. Two approaches of DNA-based method are widely used, bulk-sample metabarcoding the use of bulk tissues such as insects and eDNA the use of environmental samples such as air, water and soil. Despite the novelty of this approach for routine freshwater biomonitoring, questions still need to be answered about its applicability and reliability due to confounding factors, e.g., sample type, laboratory technicalities, and limitations of databases. Hence, studies on direct comparisons are essential to validate the efficiency of these molecular approaches compared to the conventional morphological approach to accurately assessed biodiversity for riverine benthic macroinvertebrate biomonitoring. This study used three approaches to estimate diversity and composition of benthic macroinvertebrates. We also evaluated the relationship between benthic macroinvertebrate communities and environmental factors. We morphologically identified 8,052 individuals from 35 families, 31 genera, and 29 species. eDNA metabarcoding identified 51 families, 84 genera, and 90 species, while 37 families, 55 genera, and 107 species were detected through bulk-sample metabarcoding. We report that bulk-sample metabarcoding showed finer taxonomic resolution than other approaches. Our study highlights the use of bulk-sample metabarcoding for macroinvertebrate biodiversity assessment.
Turing pattern formation in reaction-cross-diffusion systems with a bilayer geometry
Authors: Diez Antoine , Krause Andrew L. , Maini Philip K. , Gaffney Eamonn A. , Seirin-Lee Sungrim 
Published: May 2023

AbstractConditions for self-organisation via Turing’s mechanism in biological systems represented by reaction-diffusion or reaction-cross-diffusion models have been extensively studied. Nonetheless, the impact of tissue stratification in such systems is under-explored, despite its ubiquity in the context of a thin epithelium overlying connective tissue, for instance the epidermis and underlying dermal mesenchyme of embryonic skin. In particular, each layer can be subject to extensively different biochemical reactions and transport processes, with chemotaxis – a special case of cross- diffusion – often present in the mesenchyme, contrasting the solely molecular transport typically found in the epidermal layer. We study Turing patterning conditions for a class of reaction-cross- diffusion systems in bilayered regions, with a thin upper layer and coupled by a linear transport law. In particular, the role of differential transport through the interface is explored together with the presence of asymmetry between the homogeneous equilibria of the two layers. A linear stability analysis is carried out around a spatially homogeneous equilibrium state in the asymptotic limit of weak and strong coupling strengths, where quantitative approximations of the bifurcation curve can be computed. Our theoretical findings, for an arbitrary number of reacting species, reveal quantitative Turing conditions, highlighting when the coupling mechanism between the layered regions can either trigger patterning or stabilize a homogeneous equilibrium regardless of the inde- pendent patterning state of each layer. We support our theoretical results through direct numerical simulations, and provide an open source code to explore such systems further.
Learning dynamic image representations for self-supervised cell cycle annotation
Authors: Ulicna Kristina , Kelkar Manasi , Soelistyo Christopher J , Charras Guillaume T , Lowe Alan R 
Published: May 2023

AbstractTime-based comparisons of single-cell trajectories are challenging due to their intrinsic heterogeneity, autonomous decisions, dynamic transitions and unequal lengths. In this paper, we present a self-supervised framework combining an image autoencoder with dynamic time series analysis of latent feature space to represent, compare and annotate cell cycle phases across singlecell trajectories. In our fully data-driven approach, we map similarities between heterogeneous cell tracks and generate statistical representations of single-cell trajectory phase durations, onset and transitions. This work is a first effort to transform a sequence of learned image representations from cell cycle-specific reporters into an unsupervised sequence annotation.