bluuebunny/crossref_metadata_2025_split huggingface dataset:
In SituSingle-Cell Spatial Profiling of Matrisome Gene Expression in Glioblastoma
Authors: De Arpan , Forero Santiago A. , Sebastian Sumod , Morales John E. , De La Fuente-Granada Marisol , Huse Jason T. , Ballester Leomar Y. , Weinberg Jeffrey S. , Lang Frederick F. , Akdemir Kadir C. , McCarty Joseph H. 
Published: November 2024

AbstractGlioblastoma (GBM) is the most common and aggressive primary brain cancer in adults, characterized by robust infiltrative growth and invasion within the neural microenvironment. While various stromal cells, including astrocytes, microglia, and vascular cells in the microenvironment, communicate with GBM cells to promote growth and invasion, relatively less is known about another critical component of the tumor stroma: the extracellular matrix (ECM). The matrisome comprises hundreds of ECM genes and affiliated adhesion and signaling components; however, little is understood about (i) the repertoire of matrisome genes and proteins expressed in GBM, (ii) the stromal and cancer cells of origin that express different matrisome factors, and (iii) how these components are interconnected to drive tumor malignancy. Here, we have used in situ single-cell transcriptomics to analyze the spatial expression of nearly 350 genes that constitute the human brain matrisome. Our efforts have identified several differentially expressed matrisome genes involved in ECM adhesion and signaling between cancer and stromal cells. Additionally, matrisome genes associated with low-grade glioma pathogenesis and progression to high-grade GBM have been identified and spatially mapped. Collectively, these experiments reveal the single-cell origins of differentially expressed ECM biomarkers as well as their spatial expression patterns in brain tumors. These findings may lead to new therapeutic efforts to inhibit matrisome components to benefit patients with malignant brain cancer.
Ex VivoDelivery of mRNA to Immune CellsViaa Non-Endosomal Route Obviates the Need for Nucleoside Modification
Authors: Ghoshal Bartika , Chakraborty Debajyoti , Nag Manish , Varadarajan Raghavan , Jhunjhunwala Siddharth 
Published: November 2024

AbstractBase modification and the use of lipid nanoparticles (LNPs) are thought to be essential for efficientin vivodelivery and expression of mRNA. However, forex vivoimmune cell engineering, the need for either of the two is unclear. Previous reports have suggested that nucleic acids may be efficiently delivered to immune cellsex vivo,through a non-endosomal delivery route, but the need for base modification has not been determined. Herein, we demonstrate that when a non-endosomal delivery method is used, unmodified mRNA performs equally well to the commonly used base-modified mRNA, including theN1methyl pseudo-uridine modification, in terms of protein expression and inflammatory response in cells. However, if an endosomal delivery route is used, thenN1methyl pseudo-uridine modification is necessary for high expression and low inflammatory response, as demonstrated by others as well. Overall, we show that non-endosomal mRNA delivery renders nucleoside modifications non-essential, and that unmodified mRNA combined with non-endosomal delivery route may be used for efficientex vivomRNA-based engineering of immune cells.
Quantifying the nuclear localisation of fluorescently tagged proteins
Authors: Hurbain Julien , ten Wolde Pieter Rein , Swain Peter S. 
Published: November 2024

AbstractCells are highly dynamic, continually responding to intra- and extracellular signals. Monitoring and measuring the response to these signals at the single-cell level is challenging. Signal transduction is fast, but reporters for downstream gene expression are typically slow, requiring fluorescent proteins to be expressed and to mature. An alternative is to fluorescently tag and then monitor the intracellular locations of transcription factors and other effectors. These proteins move in or out of the nucleus in minutes, after upstream signalling modifies their state of phosphorylation. Although such approaches are being used increasingly, there is no consensus on how to quantify the nuclear and cytoplasmic localisation of these proteins. Using budding yeast, we developed a convolutional neural network that quantifies nuclear localisation from fluorescence and, optionally, bright-field images. Focusing on the cellular response to changing glucose, we generated ground-truth data using strains with both a transcription factor and a nuclear protein tagged with fluorescent markers. We then showed that the neural network based approach outperformed seven published methods, particularly when predicting single-cell time series, which are key to determining how cells respond and adapt. Collectively, our results are conclusive — using machine learning to automatically determine the appropriate image processing consistently outperforms ad hoc methods. Adopting such methods promises to both improve the accuracy and, with transfer learning, the consistency of single-cell analyses.
The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to primary cilia
Authors: Linnert Joshua , Kusuluri Deva Krupakar , Güler Baran E. , Patnaik Sarita Rani , May-Simera Helen L. , Wolfrum Uwe 
Published: November 2024

AbstractPrimary cilia are antenna-like sensory organelles present on almost all eukaryotic cells. Their sensory capacity relies on receptors, in particular G-protein-coupled receptors (GPCRs) which localize to the ciliary membrane. Here we show that ADGRV1, a member of the GPCR subfamily of adhesion GPCRs, is part of a large protein network, interacting with numerous proteins of a comprehensive ciliary proteome. ADGRV1 is localized to the base of prototypic primary cilia in cultured cells and the modified primary cilia of retinal photoreceptors, where it interacts with TRiC/CCT chaperonins and the Bardet Biedl syndrome (BBS) chaperonin-like proteins. Knockdown of ADGRV1, CCT2 and 3, and BBS6 result in common ciliogenesis phenotypes, namely reduced ciliated cells combined with shorter primary cilia. In addition, the localization of ADGRV1 to primary cilia depends on the activity of a co-complex of TRiC/CCT chaperonins and the BBS chaperonin-like proteins. In the absence of components of the TRiC/CCT-BBS chaperonin co-complex, ADGRV1 is depleted from the base of the primary cilium and degraded via the proteasome. Defects in the TRiC/CCT-BBS chaperonin may lead to an overload of proteasomal degradation processes and imbalanced proteostasis. Dysfunction or absence of ADGRV1 from primary cilia may underly the pathophysiology of human Usher syndrome type 2 and epilepsy caused by mutations inADGRV1.
Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability
Authors: Sannigrahi Malay K. , Raghav Lovely , Rich Dominick J. , Schrank Travis P. , Califano Joseph A. , Lukens John N. , Sun Lova , Morgan Iain M. , Cohen Roger B. , Lin Alexander , Liu Xinyi , Brown Eric J. , You Jianxin , Mirabello Lisa , Mishra Sambit K. , Shimunov David , Brody Robert M , Pearson Alexander T. , Gimotty Phyllis A. , Diab Ahmed , Jalaly Jalal B. , Basu Devraj 
Published: November 2024

ABSTRACTBackgroundLimited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.Methods50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced. Groups were compared by gene set enrichment analysis, and select differences were validated by immunohistochemistry. Features discriminating groups were scored in each tumor using gene set variation analysis, and scores were evaluated for recurrence prediction ability.ResultsCases downregulated pathways linked to anti-tumor immunity (FDR-adjusted p<.05) and contained fewer tumor-infiltrating lymphocytes (p<.001), including cytotoxic T-cells (p=.005). Cases also upregulated pathways related to cell division and other aspects of tumor progression. Upregulated and downregulated pathways were respectively used to define a tumor progression score (TPS) and immune suppression score (ISS) for each tumor. Correlation between TPS and ISS (r=.603, p<.001) was potentially explained by observed upregulation of DNA repair pathways in cases, which might enhance their progression directly and by limiting cytosolic DNA-induced inflammation. Accordingly, cases contained fewer double-strand breaks based on staining for phospho-RPA32 (p=.006) and γ-H2AX (p=.005) and downregulated pro-inflammatory components of the cytoplasmic DNA sensing pathway. A combined score derived from TPS and ISS optimized recurrence prediction and stratified survival in a manner generalizable to three external cohorts.ConclusionsWe provide novel evidence that limiting genomic instability makes tumor-intrinsic and immune-mediated contributions to HPV+ OPSCC recurrence risk, opening opportunities to detect and target this treatment-resistant biology.
Meta-atlas of Juvenile and Adult Enteric Neuron scRNA-seq for Dataset Comparisons and Consensus on Transcriptomic Definitions of Enteric Neuron Subtypes
Authors: Benthal Joseph T. , May-Zhang Aaron A. , Southard-Smith E. Michelle 
Published: November 2024

ABSTRACTBackgroundThe enteric nervous system (ENS) is a complex network of interconnected ganglia within the gastrointestinal (GI) tract. Among its diverse functions, the ENS detects bowel luminal contents and coordinates the passing of stool. ENS defects predispose to GI motility disorders. Previously, distinct enteric neuron types were cataloged by dye-filling techniques, immunohistochemistry, retrograde labeling, and electrophysiology. Recent technical advances in single cell RNA-sequencing (scRNA-seq) have enabled transcriptional profiling of hundreds to millions of individual cells from the intestine. These data allow cell types to be resolved and compared to using their transcriptional profiles (“clusters”) rather than relying on antibody labeling. As a result, greater diversity of enteric neuron types has been appreciated. Because each scRNA-seq study has relied on different methods for cell isolation and library generation, numbers of neuron clusters and cell types detected differs between analyses. Cell counts in each dataset are particularly important for characterization of rare cell types since small numbers of profiled cells may not sample rare cell types. Importantly, each dataset, depending on the isolation methods, may contain different proportions of cells that are not detected in other datasets. Aggregation of datasets can effectively increase the total number of cells being analyzed and can be helpful for confirming the presence of low-abundance neuron types that might be absent or observed infrequently in any single dataset.ResultsHere we briefly systematically review eachMus musculussingle cell or single nucleus RNA-sequencing enteric nervous system dataset. We then reprocess and computationally integrate these select independent scRNA-seq enteric neuron datasets with the aim to identify new cell types, shared marker genes across juvenile to adult ages, dataset differences, and achieve some consensus on transcriptomic definitions of enteric neuronal subtypes.ConclusionsData aggregation generates a consensus view of enteric neuron types and improves resolution of rare neuron classes. This meta-atlas offers a deeper understanding of enteric neuron diversity and may prove useful to investigators aiming to define alterations among enteric neurons in disease states. Future studies face the challenge of connecting these deep transcriptional profiles for enteric neurons with historical classification systems.
Source amplitude increases with body mass across avian genera
Authors: Ziegenhorn Morgan A. , Lanctot Richard B. , Brown Stephen C. , Saalfeld Sarah T. , Smith Paul A. , Lecomte Nicolas 
Published: November 2024

AbstractAmplitude, or intensity, of sound is a fundamental characteristic of inter acoustic communication, with relevance in many scientific fields. The amplitude of an animal’s acoustic signal at its source (“source amplitude”) may be particularly relevant in the field of acoustic allometry, where relationships between species’ physical and acoustic features (e.g., dominant frequency) have been well-established across taxa. However, despite their potential scientific value, records and studies of source amplitudes remain remarkably scarce for avian species. Here we present novel estimates of source amplitude (range, mean, and median) for 17 species of Arctic-breeding birds, derived from measurements made in Utqiaġvik, Alaska during June 2024. We found a strong positive correlation between body mass and source amplitude in this data via a Markov Chain Monte Carlo multivariate generalized linear mixed model (MCMCglmm). Both phylogeny and individual identity were important random effects in this model. In contrast, random effects from environmental factors and measurement characteristics were minimal. Our work represents the first model describing the relationship between source amplitude and allometry across avian genera. We hope that this study will spur other investigations into avian source amplitude and its relationship to morphological and life history features for species in the Arctic and elsewhere.
High-throughput measurement of adipocyte size with open-source software using whole-slide adipose tissue images
Authors: Alan Ramalho , Marie-Frédérique Gauthier , Ina Maltais-Payette , Giada Ostinelli , Frédéric Hould , Laurent Biertho , André Tchernof 
Published: November 2024

AbstractThe aim of this study was to create and validate a high-throughput method based on open-source software for the measurement of adipocyte diameters in white adipose tissue histological sections. Human omental and subcutaneous adipose tissue samples collected during bariatric surgery were used to prepare hematoxylin and eosin-stained histological slides. Digital images were acquired. Adipocyte diameters were measured both manually and with an automated procedure created using ImageJ. Comparative analysis of our automated method with the manual measurement and associations of the mean adipocyte diameters with cardiometabolic markers were used to validate our method. A total of 377 adipose samples (190 participants) were included in the analysis. Pearson correlation of mean adipocyte diameters shows a strong linear relationship between methods (r=0.88, p<0.0001). The average diameter measured with the automated method was significantly smaller (8.1±5.3µm difference, p<0.0001) compared to the manual method, likely reflecting bias in selecting the cells measured with the manual approach. Pearson correlation analyses between mean omental adipocyte diameters and markers of cardiometabolic risk show that the diameters of both methods are significantly associated with the same parameters (fasting concentrations of TG, HDL-Chol, homeostasis model assessment insulin resistance, and visceral adiposity index values) with no significant differences between methods. There were also no significant differences between the manual and automated method regarding the correlations between mean subcutaneous adipocyte diameters and anthropometric or metabolic markers. In conclusion, we have created and validated a rapid automated method based on open-source software to measure adipocyte diameters from whole-slide adipose tissue images.
Epigenetic silencing and host genome evolution determine fate of viral insertions inAcanthamoeba
Authors: Blais Cédric , Colp Morgan J. , Sarre Luke A. , de Mendoza Alex , Archibald John M. 
Published: November 2024

ABSTRACTAcanthamoebais a cosmopolitan freshwater amoebae known for its association with Nucleocytoplasmic Large DNA Viruses (NCLDVs). Previous studies have shown thatAcanthamoebaspp. undergo lateral gene transfer (LGT) with NCLDVs. Here we have leveraged chromosome-scale assemblies of two strains ofAcanthamoeba castellanii, Neff and C3, to investigate the occurrence and genomic context of viral LGT inAcanthamoeba. We show that the viral ‘footprints’ in the C3 and Neff genomes are largely non-overlapping and that viral genes in Neff are found disproportionately in large sub-telomeric insertions. Multiple partial copies of these insertions are found throughout the Neff genome, but they are not expressed and do not encode functions for their own mobility. Viral regions are hyper-methylated and highly condensed, suggesting that the expression of recently acquired viral DNA is suppressed in heterochromatic regions. We propose a three-step model for the origin and fate of viral sequences inAcanthamoeba: (i) integration of DNA from giant viruses, (ii) epigenetic suppression of the viral DNAs, which allows them to persist in the genome, and (iii) deterioration of viral genomes by point mutation and intra- and inter-chromosomal recombination. Viral integrations inAcanthamoebaspp. are transient and may not have long-lasting effects on the fitness of the host amoeba. Our work strengthens a growing body of work showing widespread but transient integration of viral DNA in protists and extends the relevance of epigenetic silencing mechanisms to the evolution ofAmoebozoa. We highlight the importance of host genome dynamics for understanding the evolution of endogenized viral elements.
Mapping lineage-resolved scRNA-seq data with spatial transcriptomics using TemSOMap
Authors: Pan Xinhai , Danies-Lopez Alejandro , Zhang Xiuwei 
Published: November 2024

AbstractSpatial transcriptomics (ST) has become a powerful technique that advances the study of cell spatial organization and cell-cell interactions. While ST can preserve location information of cells or spots, limitations of such technologies include lower number of genes, and lower resolution compared to scRNA-seq datasets. These limitations can be alleviated by integrating scRNA-seq data with the ST data. By mapping the single cells onto the spatial data, we can infer the spatial coordinates of the cells from the scRNA-seq dataset. We consider leveraging temporal information in this challenging task of spatial location inference. During tissue formation, cells divided from the same ancestor are likely to be located close to each other in the tissue, thus the cell clonal or lineage information can improve cell location inference. CRISPR/Cas9-based lineage tracing technologies have enabled paired sequencing of cells’ gene expression and lineage barcodes. The lineage barcodes can be used to reconstruct the cell lineage tree, which represents cells’ clonal relationships. In order to incorporate this information, we developed TemSOMap (Temporal dynamics guidedSpatialOmicsMapping), which infers the spatial coordinates of cells by mapping a paired gene expression and lineage barcode dataset onto a spatial transcriptomics dataset. TemSOMap utilizes a machine learning framework to infer a cell-to-spot mapping matrix by minimizing a loss function based on expression and lineage. We show that TemSOMap more accurately infers the spatial location of single cells compared to state-of-the-art baseline methods under various scenarios, using both simulated and real datasets. The resulting lineage-resolved ST data can help us better understand the spatio-temporal dynamics of cells in a tissue. TemSOMap is publicly available athttps://github.com/ZhangLabGT/TemSOMap.
Phytoassisted synthesis of biogenic silver nanoparticles usingVernonia amygdalinaleaf extract: characterization, antibacterial, anti-inflammatory, and acute toxicity profile
Authors: Gildas Fonye Nyuyfoni , Parfait Nkana Blondeau , Deli Vandi , Kedi Philippe Belle Ebanda , Antoinette Ntoumba Agnes , Christian Nanga Chick , Geordamie Chimi Tchatchouang , Guilaine Djuidje Annie , Alex Kevin Tako Djimefo , Ines Danielle Evouna Madeleine , Fanny-Aimee Essombe Malolo , Costly Kang Eha-Kang , Leonard Kwati , Ndzeidze Gilbert Njowir , Awawou Paboudam Gbambie , Francois Eya’ane Meva 
Published: November 2024

ABSTRACTThe increasing rate of antimicrobial resistance and pathological consequences associated with long-term use of available anti-inflammatory drugs justifies the urgent need to discover and rationally design new effective antimicrobial and anti-inflammatory drugs. This study reports the antibacterial, anti-inflammatory, and acute toxicity profile ofVernonia amygdalinaleaf extract-mediated silver nanoparticles (VA-AgNPs).The VA-AgNPs were synthesized by mixing Ag+ions with aqueous leaf extract fromVernonia amygdalinaand then characterized using UV-visible spectrophotometry (UV-Vis), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). An antibacterial study onEscherichia colistrains, carrageenan-induced rat paw edema, and oral acute toxicity assays were performed. The change in color from light brown to dark brown showed the formation of VA-AgNPs which was further confirmed by the surface plasmon resonance picked between 400 and 450 nm on the UV-Vis spectrum. Synthetic stability studies revealed an increase in VA-AgNPs formation at basic pH and with increasing reactant quantities. The X-ray pattern showed nanocrystalline particles of Ag and AgCl of 13, and 18 nm mean sizes, respectively. SEM images depicted aggregates of spherical shape. The synthesized VA-AgNPs inhibitedEscherichia coligrowth with a minimum inhibition concentration of 0.125 mg/mL and rat paw edema with a maximum inhibition percentage of 96% at a dose of 0.4 mg/kg body weight. The oral administration of VA-AgNPs was associated with no toxicity sign, supporting their use for the development of new effective antibacterial and anti-inflammatory drugs.
Association between loneliness and hippocampal responses to dynamic social stimuli in psychotic disorders
Authors: McKenna Faye , Vinke Louis N. , Avanaki Mona , Holt Daphne J. 
Published: November 2024

ABSTRACTBackgroundThe incidence of loneliness has increased over the past several decades worldwide and is particularly common among people with serious mental illnesses. However, this public health problem has been difficult to address, in part because the neurocognitive mechanisms underlying loneliness are poorly understood.MethodsTo investigate these mechanisms, a functional magnetic resonance imaging (fMRI) study was conducted which accounted for known cognitive biases associated with loneliness. Participants with (n = 40) and without (n = 60) psychotic disorders (PD) viewed images of faces that appeared to approach or withdraw from the participants, while fMRI data were collected. Following the scanning, participants rated the trustworthiness of the faces, and these ratings were included as weights in the fMRI analyses. Neural responses to approaching versus withdrawing faces were measured, and whole brain regression analyses, with loneliness as the regressor, were performed.ResultsIn the PD and full samples, a higher level of loneliness was significantly associated with greater responses of the hippocampus and areas of the basal ganglia to withdrawing (versus approaching) face stimuli. Moreover, the effects in the hippocampus, but not the basal ganglia, remained significant after controlling for potential confounds such as social activity levels, depression and social anhedonia. Lastly, in a subset of the sample (n = 66), greater hippocampal responses to withdrawing faces predicted greater loneliness one year later.ConclusionsHeightened responses of the hippocampus to withdrawing faces may represent a candidate objective marker of loneliness that could be modified by interventions targeting loneliness.