bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hist2Vec: Kernel-Based Embeddings for Biological Sequence Classification
Authors: Ali Sarwan , Mansoor Haris , Chourasia Prakash , Patterson Murray 
Published: August 2023

AbstractBiological sequence classification is vital in various fields, such as genomics and bioinformatics. The advancement and reduced cost of genomic sequencing have brought the attention of researchers for protein and nucleotide sequence classification. Traditional approaches face limitations in capturing the intricate relationships and hierarchical structures inherent in genomic sequences, while numerous machine-learning models have been proposed to tackle this challenge. In this work, we propose Hist2Vec, a novel kernel-based embedding generation approach for capturing sequence similarities. Hist2Vec combines the concept of histogram-based kernel matrices and Gaussian kernel functions. It constructs histogram-based representations using the uniquek-mers present in the sequences. By leveraging the power of Gaussian kernels, Hist2Vec transforms these representations into high-dimensional feature spaces, preserving important sequence information. Hist2Vec aims to address the limitations of existing methods by capturing sequence similarities in a high-dimensional feature space while providing a robust and efficient framework for classification. We employ kernel Principal Component Analysis (PCA) using standard machine-learning algorithms to generate embedding for efficient classification. Experimental evaluations on protein and nucleotide datasets demonstrate the efficacy of Hist2Vec in achieving high classification accuracy compared to state-of-the-art methods. It outperforms state-of-the-art methods by achieving > 76% and > 83% accuracies for DNA and Protein datasets, respectively. Hist2Vec provides a robust framework for biological sequence classification, enabling better classification and promising avenues for further analysis of biological data.
Characterizing the impact and maintenance of specialized toxin tolerance in a generalist species
Authors: Kropelin Grace , Scott Chialvo Clare H. 
Published: August 2023

ABSTRACTUnderstanding how plant-herbivore interactions can drive coevolution is a central goal of ecology and evolutionary biology. Of particular interest are the defenses produced by host plants/fungi and their impact on herbivore feeding strategies. In theimmigrans-tripunctataradiation ofDrosophila, mushroom-feeding species are classified as generalists, but their acceptable hosts include deadlyAmanitaspecies. In this study, we used behavioral assays to assess whether the mushroom-feeding speciesDrosophila guttiferais becoming a specialist and to characterize the impact of competition on host usage. We conducted feeding assays to confirm the presence of cyclopeptide toxin tolerance. We then completed host preference assays in female flies and larvae and did not find a preference for toxic mushrooms in either. Finally, we assessed the effect of competition on oviposition preference. We found that the presence of a competitor’s eggs on the preferred host was associated with the flies increasing the number of eggs laid on the toxic mushrooms. Our results suggest that an adaptation associated with specialized feeding behavior is not altering host usage and that competition plays a role in maintaining this trait. More broadly our work highlights how access to a low competition host resource helps to maintain adaptations with fitness costs.
Non-Invasive Perfusion MR Imaging of the Human Brain via Breath-Holding
Authors: Schulman J.B. , Kashyap S. , Kim S.G. , Uludağ K. 
Published: August 2023

AbstractDynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3T and 7T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3T vs 8.5 at 7T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.
Heroes and villains: opposing narrative roles engage neural synchronization in the lateral inferior frontal gyrus
Authors: Ryu Hayoung , Kim M. Justin 
Published: August 2023

AbstractNeuroscientific studies have highlighted the role of the default mode network (DMN) in processing narrative information. Here, we examined whether the neural synchronization of the DMN tracked the appearances of characters with different narrative roles (i.e., protagonists versus antagonists) when viewing highly engaging, socially rich audiovisual narratives. Using inter-subject correlation analysis on two independent, publicly available movie-watching functional magnetic resonance imaging datasets (SherlockandThe Grand Budapest Hotel), we computed whole-brain neural synchronization during the appearance of the protagonists and antagonists. Results showed that the inferior frontal gyrus (IFG) and orbitofrontal cortex (OFC), which are components of the DMN, had higher ISC values during the appearance of the protagonists compared to the antagonists. Importantly, these findings were commonly observed in both datasets. We discuss the present results in the context of information integration and emotional empathy, which are relevant functions known to be supported by the DMN. Our study presents generalizable evidence that regions within the DMN – particularly the IFG and OFC – show distinctive synchronization patterns due to differences in narrative roles.
A hybrid machine learning and regression method for cell type deconvolution of spatial barcoding-based transcriptomic data
Authors: Liu Yunqing , Li Ningshan , Qi Ji , Xu Gang , Zhao Jiayi , Wang Nating , Huang Xiayuan , Jiang Wenhao , Justet Aurélien , Adams Taylor S. , Homer Robert , Amei Amei , Rosas Ivan O. , Kaminski Naftali , Wang Zuoheng , Yan Xiting 
Published: August 2023

AbstractSpatial barcoding-based transcriptomic (ST) data require cell type deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method, to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER uses a machine learning approach to remove the systematic difference between ST and scRNA-seq data (platform effects) explicitly and efficiently to ensure the linear relationship between ST data and cell type-specific expression profile. It also considers sparsity of cell types per capture spot and across-spots spatial correlation in cell type compositions. Based on the estimated cell type proportions, SDePER imputes cell type compositions and gene expression at unmeasured locations in a tissue map with enhanced resolution. Applications to coarse-grained simulated data and four real datasets showed that SDePER achieved more accurate and robust results than existing methods, suggesting the importance of considering platform effects, sparsity and spatial correlation in cell type deconvolution.
Quantitative image analysis pipeline for detecting circulating hybrid cells in immunofluorescence images with human-level accuracy
Authors: Heussner Robert T. , Whalen Riley M. , Anderson Ashley , Theison Heather , Baik Joseph , Gibbs Summer , Wong Melissa H. , Chang Young Hwan 
Published: August 2023

AbstractCirculating hybrid cells (CHCs) are a newly discovered, tumor-derived cell population identified in the peripheral blood of cancer patients and are thought to contribute to tumor metastasis. However, identifying CHCs by immunofluorescence (IF) imaging of patient peripheral blood mononuclear cells (PBMCs) is a time-consuming and subjective process that currently relies on manual annotation by laboratory technicians. Additionally, while IF is relatively easy to apply to tissue sections, its application on PBMC smears presents challenges due to the presence of biological and technical artifacts. To address these challenges, we present a robust image analysis pipeline to automate the detection and analyses of CHCs in IF images. The pipeline incorporates quality control to optimize specimen preparation protocols and remove unwanted artifacts, leverages a β-variational autoencoder (VAE) to learn meaningful latent representations of single-cell images and employs a support vector machine (SVM) classifier to achieve human-level CHC detection. We created a rigorously labeled IF CHC dataset including 9 patients and 2 disease sites with the assistance of 10 annotators to evaluate the pipeline. We examined annotator variation and bias in CHC detection and then provided guidelines to optimize the accuracy of CHC annotation. We found that all annotators agreed on CHC identification for only 65% of the cells in the dataset and had a tendency to underestimate CHC counts for regions of interest (ROI) containing relatively large amounts of cells (>50,000) when using conventional enumeration methods. On the other hand, our proposed approach is unbiased to ROI size. The SVM classifier trained on the β-VAE encodings achieved an F1 score of 0.80, matching the average performance of annotators. Our pipeline enables researchers to explore the role of CHCs in cancer progression and assess their potential as a clinical biomarker for metastasis. Further, we demonstrate that the pipeline can identify discrete cellular phenotypes among PBMCs, highlighting its utility beyond CHCs.
Mutational analysis of the nitrogenase carbon monoxide protective protein CowN reveals that a conserved C-terminal glutamic acid residue is necessary for its activity
Authors: Willard Dustin L. , Arellano Joshuah J. , Underdahl Mitch , Lee Terrence M. , Ramaswamy Avinash S. , Fumes Gabriella , Kliman Agatha , Wong Emily Y. , Owens Cedric P. 
Published: August 2023

ABSTRACTNitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near CowN’s C-terminus is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and CowN’s ability to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection. Overall, this work uncovers structural features in CowN that are required for its function and provides new insights into its nitrogenase binding and CO protection mechanism.
Tribbles1 and Cop1 cooperate to protect the host duringin vivomycobacterial infection
Authors: Hammond Ffion R , Lewis Amy , Pollara Gabriele , Tomlinson Gillian S , Noursadeghi Mahdad , Kiss-Toth Endre , Elks Philip M 
Published: August 2023

AbstractTuberculosis is a major global health problem and is one of the top 10 causes of death worldwide. There is a pressing need for new treatments that circumvent emerging antibiotic resistance.Mycobacterium tuberculosisparasitises macrophages, reprogramming them to establish a niche in which to proliferate, therefore macrophage manipulation is a potential host-directed therapy if druggable molecular targets could be identified. The pseudokinase Tribbles1 (Trib1) regulates multiple innate immune processes and inflammatory profiles making it a potential drug target in infections. Trib1 controls macrophage function, cytokine production and macrophage polarisation. Despite wide-ranging effects on leukocyte biology, data exploring the roles of Tribbles in infectionin vivoare limited. Here, we identify that human Tribbles 1 is expressed in monocytes and is upregulated at the transcript level after stimulation with mycobacterial antigen. To investigate the mechanistic roles of Tribbles in the host response to mycobacteriain vivo, we used a zebrafishMycobacterium marinum(Mm) infection tuberculosis model. Zebrafish Tribbles family members were characterised and shown to have substantial mRNA and protein sequence homology to their human orthologues.trib1overexpression was host-protective against Mm infection, reducing burden by approximately 50%. Conversely,trib1knockdown exhibited increased infection. Mechanistically,trib1overexpression significantly increased the levels of pro-inflammatory factorsil-1β and nitric oxide. The host-protective effect oftrib1was found to be dependent on the E3 ubiquitin kinase Cop1. These findings highlight the importance of Trib1 and Cop1 as immune regulators during infectionin vivoand suggest that enhancing macrophage TRIB1 levels may provide a tractable therapeutic intervention to improve bacterial infection outcomes in tuberculosis.
Identification of clade-defining single nucleotide polymorphisms for improved rabies virus surveillance
Authors: Kumar Ankeet , Tushir Sheetal , Devasurmutt Yashas , Nath Sujith S , Tatu Utpal 
Published: August 2023

AbstractBackgroundRabies is an ancient disease that remains endemic in many countries. It causes many human deaths annually, predominantly in resource-poor countries. Over evolutionary timelines, several rabies virus (RABV) genotypes have stabilised, forming distinct clades. Extensive studies have been conducted on the origin, occurrence and spread of RABV clades. Single nucleotide polymorphisms (SNPs) distribution across the RABV genome and its clades remains largely unknown, highlighting the need for comprehensive whole-genome analyses.MethodsWe accessed whole genome sequences for RABV from public databases and identified SNPs across the whole genome sequences. Then, we annotated these SNPs using an R script, and these SNPs were categorised into different categories; universal, clade-specific, and clade-defining, based on the frequency of occurrence.ResultsIn this study, we present the SNPs occurring in the RABV based on whole genome sequences belonging to 8 clades isolated from 7 different host species likely to harbour dog-related rabies. We classified mutations into several classes based on their location within the genome and assessed the effect of SNP mutations on the viral glycoprotein.ConclusionsThe clade-defining mutations have implications for targeted surveillance and classification of clades. Additionally, we investigated the effects of these mutations on the Glycoprotein of the virus. Our findings contribute to expanding knowledge about RABV clade diversity and evolution, which has significant implications for effectively tracking and combatting RABV transmission.
Phylogenetically diverse wild plant species use common biochemical strategies to thrive in the Atacama Desert
Authors: Dussarrat Thomas , Nilo-Poyanco Ricardo , Moyano Tomás C. , Prigent Sylvain , Jeffers Tim L. , Díaz Francisca P. , Decros Guillaume , Audi Lauren , Sondervan Veronica M , Shen Bingran , Araus Viviana , Rolin Dominique , Shasha Dennis , Coruzzi Gloria M. , Gibon Yves , Latorre Claudio , Pétriacq Pierre , Gutiérrez Rodrigo A. 
Published: August 2023

AbstractThe best ideotypes are under mounting pressure due to increased aridity in many parts of the world. Understanding the conserved molecular mechanisms that evolve in wild plant species adapted to harsh environments is crucial in developing new strategies for sustainable agriculture. Yet our knowledge of such mechanisms in wild species is scant, particularly in extreme environments. We performed metabolic pathway reconstruction using transcriptome information from 32 Atacama plant species and phylogenetically related plant species that do not live in Atacama (Sister species). We analyzed pathway and reaction enrichment to understand the biochemical commonalities and differences of wild Atacama plant species. To gain insights into the mechanisms that ensure plant survival, we compared expressed gene isoform numbers and gene expression patterns between the annotated biochemical reactions from 32 Atacama and Sister species. We found significant biochemical convergences in primary and secondary metabolism characterized by reactions enriched in at least 50% of the Atacama species across major plant phylogenetic lineages. Analysis of the annotation indicated potential advantages against drought, salinity, high solar irradiance, and nitrogen starvation. These findings suggest that the adaptation in the Atacama Desert may result in part from shared genetic legacies governing the expression of key metabolic pathways to face harsh environmental conditions. Enriched reactions corresponded to ubiquitous compounds common to extreme and agronomic species and were congruent with our previous metabolomic analyses in these Atacama species. Hence, genes underlying these adaptive traits offer promising candidates for improving abiotic stress resilience in crop species.
The cGAS-STING pathway regulates microglial chemotaxis in genome instability
Authors: Talbot Emily J. , Joshi Lisha , Thornton Peter , Dezfouli Mahya , Tsafou Kalliopi , Perkinton Michael , Khoronenkova Svetlana V. 
Published: August 2023

ABSTRACTDefective DNA damage signalling and repair is a hallmark of age-related and genetic neurodegenerative disease. One mechanism implicated in disease progression is DNA damage-driven neuroinflammation, which is largely mediated by tissue-resident immune cells, microglia. Here, we utilise human microglia-like cell models of persistent DNA damage and ATM kinase deficiency to investigate how genome instability shapes microglial function. We demonstrate that upon DNA damage the cytosolic DNA sensing cGAS-STING axis drives chronic inflammation and a robust chemokine response, exemplified by production of CCL5 and CXCL10. Transcriptomic analyses revealed that cell migratory pathways were highly enriched upon IFN-β treatment of human iPSC-derived microglia, indicating that the chemokine response to DNA damage mirrors type I interferon signalling. Furthermore, we find that STING deletion leads to a defect in microglial chemotaxis under basal conditions and upon ATM kinase loss. Overall, this work provides mechanistic insights into cGAS-STING-dependent neuroinflammatory mechanisms and consequences of genome instability in the central nervous system.
A single base pair substitution on Chromosome 25 in zebrafish distinguishes between development and acute regulation of behavioral thresholds
Authors: Ortiz Elelbin A. , Campbell Philip D. , Nelson Jessica C. , Granato Michael 
Published: August 2023

AbstractBehavioral thresholds define the lowest stimulus intensities sufficient to elicit a behavioral response. Establishment of baseline behavioral thresholds during development is critical for proper responses throughout the animal’s life. Despite the relevance of such innate thresholds, the molecular mechanisms critical to establishing behavioral thresholds during development are not well understood. The acoustic startle response is a conserved behavior whose threshold is established during development yet is subsequently acutely regulated. We have previously identified a zebrafish mutant line (escapist) that displays a decreased baseline or innate acoustic startle threshold. Here, we identify a single base pair substitution on Chromosome 25 located within the coding sequence of thesynaptotagmin 7a(syt7a) gene that is tightly linked to theescapistacoustic hypersensitivity phenotype. By generating animals in which we deleted thesyt7aopen reading frame, and subsequent complementation testing with theescapistline, we demonstrate that loss ofsyt7afunction is not the cause of theescapistbehavioral phenotype. Nonetheless,escapistmutants provide a powerful tool to decipher the overlap between acute and developmental regulation of behavioral thresholds. Extensive behavioral analyses reveal that inescapistmutants the establishment of the innate acoustic startle threshold is impaired, while regulation of its acute threshold remains intact. Moreover, our behavioral analyses reveal a deficit in baseline responses to visual stimuli, but not in the acute regulation of responses to visual stimuli. Together, this work eliminates loss ofsyt7aas causative for theescapistphenotype and suggests that mechanisms that regulate the establishment of behavioral thresholds inescapistlarvae can operate largely independently from those regulating acute threshold regulation.
Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence
Authors: Salinas-Pena Mónica , Rebollo Elena , Jordan Albert 
Published: August 2023

AbstractHistone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of rDNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.