bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning enabled discovery of kinase drug targets in Pharos
Authors: Halász Ádám M. , Mathias Stephen L. , Das Srinjoy , Edwards Jeremy S. 
Published: October 2024

AbstractWe use machine learning with standardized molecular structure and gene ontology data to predict ligand interactions for a set of human kinases. We realize this by leveraging information from the TCRD / Pharos database, developed and maintained within the Illuminating the Druggable Genome (IDG) project.Pharos collects relevant biochemical and clinically relevant information of a large set of biologically important (human) proteins from publicly available sources, including scientific publications as well as specialized databases. The 635 kinases listed in Pharos are classified into levels reflecting the relative amount and type of accumulated information. Importantly, molecular structure and Gene Ontology annotations are available for the entire set, but only 455 of the kinases have recorded ligand affinity data.We developed a deep neural network-based framework to predict the ligand affinity profile for kinases using generally available information (molecular structure and Gene Ontology annotations) as input. The input data is organized into a 2,770 – dimensional vector with binary entries. The output data are predicted affinity values for interactions between the respective kinase and possible ligands.To address the very large number of possible ligands (58,800) and the sparsity of available binding data, we organized the ligands into 5,275 clusters based on structural similarity measures. Our model framework is trained to predict likely interactions between kinases and these ligand clusters.We aim to identify sets of likely ligand partners associated with high predicted relative affinities for a given kinase. We measure performance by evaluating the efficiency in identifying known ligand partners for documented kinases that were not included in the training data. Our results indicate that our model framework can identify sets of ligands that will contain a significant fraction of the correct (known) ligand partners.
BioFunctional: A Comprehensive App for Interpreting and Visualizing Functional Analysis of KEGG Pathways and Gene Ontologies
Authors: Rodriguez Alejandro , Monleon Getino Antonio 
Published: October 2024

AbstractA comprehensive application designed for the interpretation and visualization of the functional analysis related to KEGG pathways and gene ontologies gives researchers and specialists a tool to get detailed functional information about their data, specifically going deep into biological pathways and gene functions information. By using a variety of techniques and libraries, such as Shiny, htrr, dplyr, tibble, and rvest, we have developed an application that provides a well-designed user-oriented interface with all the facilities to assess their data and start analyzing it directly from scratch through a few steps.The software allows an exhaustive exploration of KEGG pathways and Gene Ontologies, facilitating the analysis of complex biological processes. To achieve this, functions described in the scripts integrate data manipulation methods and web scraping techniques to extract the necessary information from online official databases, Kyoto Encyclopedia of Genes and Genomes (KEGG) and QuickGo. Furthermore, those functions are computed by parallel processing, resulting in efficient petitions to the database servers and allowing the user to get quick results from a large dataset.A crucial feature of BioFunctional is its ability to obtain ancestral information for KEGG pathways and gene ontologies, using the techniques described above. This makes it easier to understand the hierarchy of these ontologies and how each sample in a dataset is classified within them, offering users a way to study the dataset at different taxonomic levels directly from the raw data. Additionally, the app implements the capability to create interactive networks, representing all experimental data to visualize the relationships between groups and ontologies without neglecting the established classification. This is a primary tool for understanding the meaning of the relationships observed within the displayed system.Key features of Biofunctional includeInteractive visualization: Create and explore networks to visualize relationships between groups and ontologies.Hierarchical analysis: Trace ancestral information for KEGG pathways and Gene Ontologies to understand hierarchical classifications.Efficient processing: Employ parallel processing for rapid data analysis, even with large datasets.Intuitive interface: A user-friendly design simplifies data exploration and analysis.Due to these attributes, the software represents a valuable tool for analysts involved in the study of KEGG pathways and Gene Ontologies. By providing an intuitive interface with advanced data processing techniques, it empowers researchers to unravel the intricacies of biological functions and gain insights into the relationships between genes or molecular components.Supplementary informationhttps://github.com/alexrodriguezmena/BIOFunctional
Evidence that the cell glycocalyx envelops respiratory syncytial virus (RSV) particles that form on the surface of RSV-infected human airway cells
Authors: Lai Soak Kuan , Lee Zhi Qi , Tan Trina Isabel , Tan Boon Huan , Sugrue Richard J 
Published: October 2024

AbstractWe examined how respiratory syncytial virus (RSV) particles circumvent the overlying glycocalyx on virus-infected A549 cells. The glycocalyx was detected using the lectin WGA-AL488 probe, and the antibodies anti-HS and anti-syndecan-4 that detect heparin sulphate (HS) and the syndecan-4 protein (SYND4) respectively. Imaging of RSV-infected cells provided evidence that the glycocalyx envelopes the virus filaments as they form, and that components of the glycocalyx such as HS moieties and SYND4 are displayed on the surface of the mature virus filaments. Using recombinant expression of the G protein we also demonstrated that the G protein was trafficked into pre-existing filamentous cellular structures with a well-defined glycocalyx, suggesting that the glycocalyx is maintained at the site of virus particle assembly. These data provide evidence that during RSV particle assembly the virus filaments become enveloped by the glycocalyx, and that the glycocalyx should be considered as a structural component of RSV particles.
Reproductive experience drives changes in behavior and physiology in male California mice (Peromyscus californicus)
Authors: Colt Maria E. , Agarwal Priyanka , Kolb David , Glasper Erica R. , Fisher Heidi S. 
Published: October 2024

AbstractPaternal experience improves memory and reduces anxiety-like behavior in males, but it is unclear whether these changes are due to mating, siring offspring, or caregiving behavior. Likewise, paternal males have larger testes, a measure of sperm production, but again, the effects of siring and caregiving experience are difficult to disentangle. We examined behavioral and physiological outcomes in three groups of male mice: 1) virgins, 2) males paired with sterile females (‘non-fathers’), and 3) experienced fathers (Experiment 1). Compared to virgins and non-fathers, experienced fathers exhibited increased recognition memory (novel object recognition) and decreased anxiety-like behavior (elevated plus maze). Virgin males, however, had smaller testes and fewer sperm compared to non-fathers. We then compared the same traits in three additional groups of male mice: 1) non-fathers, 2) non-fathers with experience caring for unrelated pups (‘pup-sensitized non-fathers’), and 3) first-time fathers, to determine whether the behavioral and physiological observations in Experiment 1 were due to siring offspring or caregiving, and how rapidly these changes occur (Experiment 2). Recognition memory and anxiety-like behavior did not differ among these three groups, suggesting that caring for a single litter does not recapitulate the behavioral changes observed in experienced fathers (Experiment 1). Despite equal mating opportunity, we observed larger testes in first-time fathers compared to non-fathers, suggesting that investment in sperm production may be more plastic than behavioral changes. Finally, we compared pup interactions in pup-sensitized non-fathers and first-time fathers. While pup-sensitized non-fathers were slower to approach pups than first-time fathers, they spent more time grooming pups, whereas first-time fathers invested more time in nest building, suggesting different caregiving behaviors in pup-sensitized males and biological fathers. Taken together, our study revealed that mating, siring, and caregiving experience contributes to changes in memory, anxiety-like behavior, and reproductive investment in males of a biparental species.
Torsion-Induced Traumatic Optic Neuropathy (TITON): A Physiologically Relevant Animal Model of Traumatic Optic Neuropathy
Authors: Ryan Annie K. , Asemota Brooke I. , Heisler-Taylor Tyler , Mello Claire , Rodriguez Luis , Sponsel William E. , Racine Julie , Rex Tonia S. , Glickman Randolph D. , Reilly Matthew A. 
Published: October 2024

AbstractTraumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. Future studies will utilize this animal model for evaluation of candidate treatments.
An atlas of conserved transcription factor binding sites reveals the cell type-resolved gene regulatory landscape of flowering plants
Authors: Baumgart Leo A , Morales-Cruz Abraham , Greenblum Sharon I , Wang Peng , Zhang Yu , Yang Lin , Chen Cindy , Dilworth David J , Garretson Alexis C , Grosjean Nicolas , He Guifen , Savage Emily , Yoshinaga Yuko , Blaby Ian K , Daum Chris G , O’Malley Ronan C 
Published: October 2024

SummaryTranscription factors (TFs) play a central role in regulating gene expression, a process fundamental to cellular function. Characterizing transcription factor binding sites (TFBSs) is essential for understanding TF functions and identifying TF target genes, but many predicted TFBSs lack clear biological significance. We generated an atlas of TFBSs across ten flowering plants and demonstrated that conserved TFBSs are strongly enriched for genomic and epigenomic signatures of functional regulatory elements. We uncovered conserved properties of TFBSs, including TF family-specific clustering of binding sites in distinct promoter and gene body locations. By integrating this atlas with single nuclei RNA and chromatin profiles, we elucidated conserved TF activity underlying development and stress responses and annotated key cell type-specific regulatory pathways. Finally, we found that TF ortholog binding specificity is preserved over long evolutionary times, suggesting that divergence of regulatory sequences, rather than TFs, is a primary driver of regulatory evolution.
Rational design of peak calling parameters for TIP-seq based on pA-Tn5 insertion patterns improves predictive power
Authors: Roberts Thomas , Dash Hiranyamaya , Rönkkö Teemu K. E. , Weinert Maria , Skene Nathan 
Published: October 2024

AbstractEpigenomic profiling provides insights into the regulatory mechanisms that govern gene expression. At a fundamental level, these mechanisms are determined by proteins that bind the DNA or modify the chromatin. Techniques such as ChIP-seq and CUT&Tag have been instrumental in mapping the binding sites of such proteins across the genome. Recent advances have led to the development of TIP-seq, a highly sensitive method devised to increase the number of unique reads per sample. Its design results in novel library features, which have not yet been explored with comparative analytics. Through the extensive assessment of bioinformatics tools and parameters we have developed an analysis pipeline that is ideally suited for TIP-seq data, including linear deduplication, read prioritisation and read shifting. Using transcription factor binding profiles (TFs), we show that our optimised pipeline greatly reduces the width of peaks to below 50% and more precisely aligns the peak summit with known motifs. A tutorial of the optimised peak calling is available on GitHub athttps://github.com/neurogenomics/peak_calling_tutorial.git. Our methodological advancement substantially improves TIP-seq data quality, and the thoughtful design of analysis parameters is widely applicable to all pA-Tn5 based profiling assays.
Basic fibroblast growth factor helps protect facial nerve cells in a freeze-induced paralysis model
Authors: Iwata Shinji , Yamada Hiroyuki , Teraoka Masato , Tanaka Takemichi , Kimura Takuya , Joko Tomonori , Tabata Yasuhiko , Wakisaka Hiroyuki , Hato Naohito 
Published: October 2024

AbstractSevere axonal damage in the peripheral nerves results in retrograde degeneration towards the central side, leading to neuronal cell death, eventually resulting in incomplete axonal regeneration and functional recovery. Therefore, it is necessary to evaluate the facial nerve nucleus in models of facial paralysis and investigate the efficacy of treatments, to identify treatment options for severe paralysis. Consequently, we aimed to examine the percentage of facial nerve cell reduction and the extent to which intratympanic administration of a basic fibroblast growth factor (bFGF) inhibits neuronal cell death in a model of severe facial paralysis. A severe facial paralysis model was induced in Hartley guinea pigs by freezing the facial canal. Animals were divided into two groups: one group was treated with gelatin hydrogel impregnated with bFGF and the other was treated with saline. Facial movement scoring, electrophysiological testing, and histological assessment of facial neurons were performed at different postoperative time points. The freezing-induced facial paralysis model showed a facial neuronal cell death rate of 29.0%; however, bFGF administration reduced neuronal cell death to 15.8%. Facial movement scores also demonstrated improvement in the bFGF group compared with those in the control group. Intratympanic bFGF administration has a protective effect on facial neurons in a model of severe facial paralysis. These findings suggest a potential therapeutic approach for treating patients with refractory facial paralysis. Further studies are required to explore the clinical applicability of this treatment.
Effects of feeding water hyacinth (Eichhornia crassipes) fodder with or without commercial concentrate on zoo-technical performance and profitability in tropical goats and sheep
Authors: Fanta Yared , Kechero Yisehak , Yemane Nebiyu 
Published: October 2024

AbstractThe utilization of unconventional feed resources, such as water hyacinth is an effective strategy to address feed shortages in tropical and subtropical regions, particularly where access to conventional feeds is limited. In this study, tropical sheep (Doyogena rams) and goats (Woyito-Guji bucks) fed diets containing different amounts of WH were examined for their zoo-technical performance and profitability sing a 2 × 4 × 4 randomized crossover design with two animal species, four nutritional treatments, and four feeding intervals. The dietary treatments consisted of 50% hay + 0% WH + 50% commercial concentrate (CC, T1), 50% hay + 12.5% WH + 37.5% CC (T2), 50% hay + 25% WH + 25% CC (T3), and 50% hay + 37.5% WH + 12.5% CC (T4). The findings showed that compared to goats, sheep had the highest energy and nutrient intake (P<0.001), nutrient digestibility (P<0.001), average daily gain (ADG, g/day), and body weight change (BWC (kg) (P<0.05). Regarding energy and nutritional intake, there was a substantial difference (P < 0.001) between treatment groups for both animal species, with the exception of goats’ consumption of DM, OM, CHO, GE, and ADL (P <0.05). Likewise, significant differences existed between treatment groups for nutritional digestibility, ADG, BWC, and FCE for both species (P <0.001). Moreover, significant interactions (P < 0.005) were seen in all energy and nutrient intake parameters between species and treatment. Furthermore, in tropical sheep and goat breeds, water hyacinth can replace up to 37.5% of the commercial concentrate used for growth and fattening, but it has a major comparative effect on sheep. Feed prices for the T4 group fed sheep and goats were 37.2% and 36.8% lower, respectively, than for the T1 group. Therefore, farmers in the tropics who cannot afford commercial concentrates can still benefit economically by using the dry biomass of water hyacinth in their diet, either with or without it.
Gut Bacteria Metabolize Natural and Synthetic Steroid Hormones via the Reductive OsrABC Pathway
Authors: Jacoby Christian , Scorza Kaylie , Ecker Lia , McMillin Mary , Ramaswamy Ramanujam , Sundararajan Anitha , Sidebottom Ashley M. , Lin Huaiying , Dufault-Thompson Keith , Hall Brantley , Jiang Xiaofang , Light Samuel H. 
Published: October 2024

ABSTRACTSteroid hormone metabolism by the gut microbiome has multiple implications for mammalian physiology, but the underlying mechanisms and broader significance of this activity remains largely unknown. Here, we isolate a novel human gut bacterium,Clostridium steroidoreducensTstrain HCS.1, that reduces cortisol, progesterone, testosterone, and related steroid hormones to 3β,5β-tetrahydrosteroid products. Through transcriptomics and heterologous enzyme profiling, we identify and biochemically characterize theC. steroidoreducensOsrABC reductive steroid hormone pathway. OsrA is a 3-oxo-Δ1-steroid hormone reductase that selectively targets the Δ1-bond present in synthetic steroid hormones, including the anti-inflammatory corticosteroids prednisolone and dexamethasone. OsrB is a promiscuous 3-oxo-Δ4-steroid hormone reductase that converts steroid hormones to 5β-dihydrosteroid intermediates. OsrC is a 3-oxo-5β-steroid hormone oxidoreductase that reduces 5β-intermediates to 3β,5β-tetrahydro products. We find thatosrAandosrBhomologs predict steroid hormone reductase activity in diverse gut bacteria and are enriched in Crohn’s disease fecal metagenomes. These studies thus identify the basis of reductive steroid hormone metabolism in the gut and establish a link between inflammatory disease and microbial enzymes that deplete anti-inflammatory corticosteroids.
DNA methylation of transposons pattern aging differences across a diverse cohort of dogs from the Dog Aging Project
Authors: Mariner Blaise L. , McCoy Brianah M. , Greenier Ashlee , Brassington Layla , Slikas Elizabeth , Adjangba Christine , Marye Abbey , Harrison Benjamin R. , Bamberger Tal , Algavi Yadid , Muller Efrat , Harris Adam , Rout Emily ,   The Dog Aging Project Consortium, Avery Anne , Borenstein Elhanan , Promislow Daniel , Snyder-Mackler Noah 
Published: October 2024

AbstractWithin a species, larger individuals often have shorter lives and higher rates of age-related disease. Despite this well-known link, we still know little about underlying age-related epigenetic differences, which could help us better understand inter-individual variation in aging and the etiology, onset, and progression of age-associated disease. Dogs exhibit this negative correlation between size, health, and longevity and thus represent an excellent system in which to test the underlying mechanisms. Here, we quantified genome-wide DNA methylation in a cohort of 864 dogs in the Dog Aging Project. Age strongly patterned the dog epigenome, with the majority (66% of age-associated loci) of regions associating age-related loss of methylation. These age effects were non-randomly distributed in the genome and differed depending on genomic context. We found the LINE1 (long interspersed elements) class of TEs (transposable elements) were the most frequently hypomethylated with age (FDR < 0.05, 40% of all LINE1 regions). This LINE1 pattern differed in magnitude across breeds of different sizes– the largest dogs lost 0.26% more LINE1 methylation per year than the smallest dogs. This suggests that epigenetic regulation of TEs, particularly LINE1s, may contribute to accelerated age and disease phenotypes within a species. Since our study focused on the methylome of immune cells, we looked at LINE1 methylation changes in golden retrievers, a breed highly susceptible to hematopoietic cancers, and found they have accelerated age-related LINE1 hypomethylation compared to other breeds. We also found many of the LINE1s hypomethylated with age are located on the X chromosome and are, when considering X chromosome inactivation, counter-intuitively more methylated in males. These results have revealed the demethylation of LINE1 transposons as a potential driver of intra-species, demographic-dependent aging variation.