bluuebunny/crossref_metadata_2025_split huggingface dataset:
The general version of Hamilton’s rule
Authors: van Veelen Matthijs 
Published: November 2024

AbstractThe generality of Hamilton’s rule1,2is much debated3–14. In this paper, I show that this debate can be resolved by constructing a general version of Hamilton’s rule, which allows for a large variety of ways in which the fitness of an individual can depend on the social behaviour of oneself and of others. For this, I first derive the Generalized Price equation, which reconnects the Price equation15with the statistics it borrows its terminology from. The Generalized Price equation moreover shows that there is not just one Price equation, but there is a Price-like equation for every possible true model. This implies that there are also multiple, nested rules to describe selection. The simplest rule is the rule for selection of non-social traits with linear fitness effects. This rule is nested in the classical version of Hamilton’s rule, for which there is consensus that it works for social traits with linear, independent fitness effects. The classical version of Hamilton’s rule, in turn, is nested in more general rules, that for instance allow for nonlinear and/or interdependent fitness effects. The general version of Hamilton’s rule therefore is a constructive solution, that allows us to accurately describe when costly cooperation evolves in a wide variety of circumstances.
VaxLLM: Leveraging Fine-tuned Large Language Model for automated annotation ofBrucellaVaccines
Authors: Li Xingxian , Zheng Yuping , Hu Joy , Zheng Jie , Wang Zhigang , He Yongqun 
Published: November 2024

AbstractBackgroundVaccines play a vital role in enhancing immune defense and preventing the hosts against a wide range of diseases. However, research relating to vaccine annotation remains a labor-intensive task due to the ever-increasing volume of scientific literature. This study explores the application of Large Language Models (LLMs) to automate the classification and annotation of scientific literature on vaccines as exemplified onBrucellavaccines.ResultsWe developed an automatic pipeline to automatically perform the classification and annotation ofBrucellavaccine-related articles, using abstract and title. The pipeline includes VaxLLM (Vaccine Large Language Model), which is a fine-tuned Llama 3 model. VaxLLM systematically classifies articles by identifying the presence of vaccine formulations and extracts the key information about vaccines, including vaccine antigen, vaccine formulation, vaccine platform, host species used as animal models, and experiments used to investigate the vaccine. The model demonstrated high performance in classification (Precision: 0.90, Recall: 1.0, F1-Score: 0.95) and annotation accuracy (97.9%), significantly outperforming a corresponding non-fine-tuned Llama 3 model. The outputs from VaxLLM are presented in a structured format to facilitate the integration into databases such as the VIOLIN vaccine knowledgebase. To further enhance the accuracy and depth of theBrucellavaccine data annotations, the pipeline also incorporates PubTator, enabling cross comparison with VaxLLM annotations and supporting downstream analyses like gene enrichment.ConclusionVaxLLM rapidly and accurately extracted detailed itemized vaccine information from publications, significantly outperforming traditional annotation methods in both speed and precision. VaxLLM also shows great potential in automating knowledge extraction in the domain of vaccine research.AvailabilityAll data is available athttps://github.com/xingxianli/VaxLLM, and the model was also uploaded to HuggingFace (https://huggingface.co/Xingxian123/VaxLLM).
Lysosomal calcium signalling contributes to the acute α-adrenergic response via calcium-stimulated adenylyl cyclase 1 and 8
Authors: Akerman Emily , Capel Rebecca A , Read Matthew , Song Qianqian , Bose Samuel J , Calamaio Serena , Aston Daniel , Koschinski Andreas , Lloyd Scott , Bell Laura , Rashbrook Victoria S , Keller Marco , Bracher Franz , Potter Barry VL , Rivolta Ilaria , Galione Antony , Sparrow Duncan B , Conti Alana , Terrar Derek A , Zaccolo Manuela , Burton Rebecca AB 
Published: November 2024

SummaryInositol trisphosphate (IP3), a calcium (Ca2+)-mobilizing second messenger, releases Ca2+from the sarcoplasmic reticulum (SR) via IP3receptors and modulates adenylyl cyclase (AC) activity in atrial myocytes. Lysosomes participate in Ca2+homeostasis by mobilising Ca2+in response to Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP). We postulate that both downstream activation of Ca2+sensitive AC (AC1 and AC8) and lysosomal Ca2+signalling in response to IP3R activation contribute to atrial myocyte function and pacemaking. Ectopic application of phenylephrine (PE) increased chronotropy and inotropy and this response was reduced in the presence of NAADP pathway inhibitors (BZ-194 and SAN4825) and Bafilomycin A1. PE increased cyclic adenosine 3’-5’ monophosphate (cAMP) activity in neonatal rat atrial myocytes (NRAMs) and this was inhibited by NAADP pathway inhibitors. This inhibition was not observed in neonatal rat ventricular myocytes (NRVMs), revealing specificity of this response to NRAMs. We investigated expression of AC1 and AC8 as a possible explanation to these observations. Genetic perturbation of AC1 and AC8 by double-knockout ofAdcy1andAdcy8in a mouse model showed a decrease in positive chronotropic and inotropic response upon cumulative dose of PE in atrial tissue, reduced PE stimulated amplitude of Ca2+transient in isolated atrial myocytes and presented decreased cytosolic cAMP levels in response to PE in neonatal atrial myocytes that was not inhibited by NAADP pathway inhibitors. Our data identifies a link between NAADP and α-adrenergic signalling pathways in atrial myocytes, highlighting that lysosomal Ca2+is an important component of α-adrenergic stimulation in the cardiac atria and warrants further investigation.
Identification and Classification of Fungal GPCR Gene Families
Authors: Liu Zhiyin , Salamov Asaf , Grigoriev Igor V. 
Published: November 2024

AbstractG protein-coupled receptors (GPCRs) are transmembrane proteins crucial for signal transduction in eu-karyotes, responding to diverse extracellular signals. Researchers have found 14 distinct types of GPCRs in fungi but their distribution among numerous fungal species remained largely unexamined. Our study identified and classified GPCRs in 1,357 fungal species, and shed light on GPCR distribution in fungi. The predominant class detected in fungi was Pth11-like GPCRs, exclusively found in Pezizomycotina and are notably acknowl-edged for their involvement in fungal pathogenicity. Our analysis suggested that Pezizomycotina ancestor possessed a more extensive array of Pth11-like GPCRs, but over time, some species underwent consider-able reductions in these GPCRs in conjunction with genome contractions. Additionally, we identified 2,089 mammalian homologs in Rhodopsin, Glutamate, and Frizzled classes across 594 fungal species, thereby augmenting the recognized fungal GPCR classes by three classes thought to be mammalian-specific. Utilizing a custom-built convolutional neural network (CNN) for the identification of fungal GPCRs, we discovered several potential novel fungal GPCRs. Moreover, anticipated interactions between these prospective new GPCRs and G-alpha proteins, as simulated by AlphaFold Multimer, offered further confirmation for these findings.
Leveraging the Human Panproteome to Enhance Peptide and Protein Identification in Proteomics and Metaproteomics
Authors: Canderan Jamie , Yuan Ruoying , Tang Haixu , Ye Yuzhen 
Published: November 2024

AbstractIn this paper, we developed a novel approach to utilize the human pangenome to improve peptide and protein identification from proteomic data (MS/MS spectra). We propose a new data structure called panproteome graph (PPG), in which nodes are tryptic peptides, to represent the human pangenome. The PPG can be built in linear time and can be utilized via graph traversal using a depth-first search algorithm to generate potential peptides for peptide identification in proteomics. The PPG built using the 47 human proteomes from the Human Pangenome Reference Consortium (HPRC) coupled with UniProt human proteins resulted in more than 4.2M tryptic peptides, a 26% increase as compared to when only the UniProt proteins were included. Graph-based analysis of the PPG revealed a giant disconnected component with about 3M nodes, suggesting substantial sharing of tryptic peptides among proteins. We applied tryptic peptides derived from PPG to characterize three collections of human proteomic and metaproteomic datasets, and our results showed that by exploiting the human pangenome, we were able to increase the number of identified peptides on all datasets we tested (about 8% increase across all three collections). We also showed that using more complete human proteome would be useful for reducing potential misidentification of human peptides as microbial peptides, a problem that was previously studied but based on genomic sequencing data. Our tool for building PPG is available in a GitHub repo PPGpep, and PPG-derived tryptic peptides can be utilized by MetaProD, a pipeline for both human and bacterial peptide and protein identification from (meta)proteomics datasets.
Mitochondrial and Microtubule Defects in Exfoliation Glaucoma
Authors: Venkatesan Arunkumar , Ridilla Marc , Castro Nileyma , Wolosin J Mario , Henty-Ridilla Jessica L. , Knox Barry E , Ganapathy Preethi S , Brown Jamin S , DeVincentis Anthony F , Sieminski Sandra , Bernstein Audrey M 
Published: November 2024

AbstractExfoliation Syndrome (XFS) is an age-related systemic condition characterized by large aggregated fibrillar material deposition in the anterior eye tissues. This aggregate formation and deposition on the aqueous humor outflow pathway are significant risk factors for developing Exfoliation Glaucoma (XFG), a secondary open-angle glaucoma. XFG is a complex, multifactorial late-onset disease that shares common features of neurodegenerative diseases, such as altered cellular processes with increased protein aggregation, impaired protein degradation, and oxidative and cellular stress. XFG patients display decreased mitochondrial membrane potential and mitochondrial DNA deletions. Here, using Tenon Capsule Fibroblasts (TFs) from Normal (No Glaucoma) and XFG patients, we found that XFG TFs have impaired mitochondrial bioenergetics and increased reactive oxygen species (ROS) accumulation. These defects are associated with mitochondrial abnormalities as XFG TFs exhibit smaller mitochondria that contain dysmorphic cristae, with an increase in mitochondrial localization to lysosomes and slowed mitophagy flux. Mitochondrial dysfunction in the XFG TFs was associated with an increase in the dynamics of the microtubule cytoskeleton, decreased acetylated tubulin, and increased HDAC6 activity. Treatment of XFG TFs with a mitophagy inducer, Urolithin A, and a mitochondrial biogenesis inducer, NAD+precursor, Nicotinamide Ribose, improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate abnormal mitochondria in XFG TFs and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients.
Constructing Probabilistic Human Mobility Patterns for Estimating Total Exposures and Pathogen Transmission Using Aggregate Mobile Phone Data
Authors: Facelli Julio C. , Gouripeddi Ram 
Published: November 2024

AbstractWhile phone location data is widely collected by providers and shared under special agreements with data aggregators, it is not available for research or routine surveillance purposes. Moreover, raw phone data may expose personal travel patterns which would not be ethically or lawful to use. One large data aggregator, Advan (https://advanresearch.com/) provides aggregate traffic patterns at weekly and monthly temporal resolution for many points of interest. This aggregate data is mostly used for commercial applications, but we argue that it can be also used to develop a model of probabilistic human mobility patterns at weekly or monthly resolution. Here we provide a stochastic algorithm that using the aggregate data provides realistic human mobility patterns at the intended temporal resolution. In the proposed model we associate a “person” with both a unique census block as the residence and another census block as the workplace. These human mobility patterns are dynamic and can be used in exposure models and in epidemiological models of epidemic spreads. Because these models do not assume any exposure or pathogen transmission mechanisms, they can be coupled to any external exposure fields or transmission model of infectious disease. Here we show how they can used to build a probabilistic model of exposure for an arbitrary exposure filed E(X, t) and a SIR contagion model. This probabilistic model can be developed at monthly or weekly time resolutions depending on the data source available and the specific programmatic needs.
RNA programmable cell targeting and manipulation with CellREADR
Authors: Yang Xiaolu , Woldemichael Kehali , Hover John , Zhao Shengli , Guo Xiao , Qian Yongjun , Gillis Jesse , Huang Z. Josh 
Published: November 2024

AbstractMethods that provide specific, easy, and scalable experimental access to animal cell types and cell states will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell. The CellREADR RNA device consists of a 5’ sensor region complementary to a cellular RNA and a 3’ payload coding region; payload translation is gated by the removal of a STOP codon in the sensor region upon base pairing with the cognate cellular RNA through an ADAR-mediated A- to-I editing mechanism ubiquitous to metazoan cells. CellREADR thus highlights the potential for RNA-based monitoring and manipulation of animal cells in ways that are simple, versatile, and generalizable across tissues and species. Here, we describe a detailed protocol for implementing CellREADR experiments in cell cultures and in animals. The procedure includes sensor and payload design, cloning, validation and characterization in mammalian cell cultures. The in vivo animal protocol focuses on AAV-based delivery of CellREADR using brain tissue as examples. We describe current best practices, various experimental controls and trouble-shooting steps. Beginning from sensor design, the validation of RNA sensor-actuators in cell cultures can be completed in 2-3 weeks. The construction of AAV vectors and their in vivo validation and characterization will take additional 6-8 weeks.
Modeling speech adaptation to altered sensory feedback through continuous learning of internal sensory predictions
Authors: Elie Benjamin , Šimko Juraj , Turk Alice 
Published: November 2024

AbstractThe paper presents a version of an optimization-based model of speech production that reproduces key acoustic and articulatory features of motorsensory adaptation to altered sensory feedback. In the presented approach, the mechanism of motorsensory adaptation is based on regular updates, based on the sensory feedback perceived by the speaker, of two of the speakers’ internal models used for computing (near)-optimal articulation. These internal models, modeled as separate Artificial Neural Networks, are 1) a model that predicts the acoustic consequences of motor (articulatory commands) and 2) a model that predicts the somatosensory sensations from given motor commands. The paper presents simulations of adaptation experiments that successfully reproduce key acoustic and articulatory features of motorsensory adaptation of speech to altered sensory feedback. These include gradual and incomplete motorsensory adaptation when the auditory (or the somatosensory) feedback is suddenly altered (F1-shifted for the altered auditory feedback, forced jaw movement for altered somatosensory feedback). The presented simulations also show that the rate and magnitude of adaptation behavior depend on a small number of parameters. Variation in the values of these parameters can potentially explain inter-speaker differences in terms of adaptation behavior, including sensory preference.
Identification of EcpK, a bacterial tyrosine pseudokinase important for exopolysaccharide biosynthesis inMyxococcus xanthus
Authors: Blöcher Luca , Schwabe Johannes , Glatter Timo , Søgaard-Andersen Lotte 
Published: November 2024

AbstractBacteria synthesize and export chemically diverse polysaccharides that function in many physiological processes and are widely used in industrial applications. In the ubiquitous Wzx/Wzy-dependent biosynthetic pathways for these polysaccharides, the polysaccharide co-polymerase (PCP) facilitates the polymerization of repeat units in the periplasm, and in Gram-negative bacteria, also polysaccharide translocation across the outer membrane. These PCPs are integral inner membrane proteins with extended periplasmic domains, and functionally depend on alternating between different oligomeric states. The oligomeric state, in turn, is determined by a cognate cytoplasmic bacterial tyrosine kinase (BYK), which is either part of the PCP or a stand-alone protein. Interestingly, BYK-like proteins, which lack key catalytic residues and/or the phosphorylated Tyr residues, have been described. InMyxococcus xanthus, the exopolysaccharide (EPS) is synthesized and exportedviathe Wzx/Wzy-dependent EPS pathway in which EpsV serves as the PCP. Here, we confirm that EpsV lacks the BYK domain. Using phylogenomics, experiments and computational structural biology, we identify EcpK as important for EPS biosynthesis and show that it structurally resembles canonical BYKs but lacks residues important for catalysis and Tyr phosphorylation. Using proteomic analyses, two-hybrid assays and structural modeling, we demonstrate that EcpK directly interacts with EpsV. Based on these findings, we suggest that EcpK is a BY pseudokinase and functions as a scaffold, which by direct protein-protein interactions, rather than by Tyr phosphorylation, facilitates EpsV function. EcpK and EpsV homologs are present in other bacteria, suggesting a broad conservation of this mechanism.ImportanceBacteria produce a variety of polysaccharides with important biological functions. In Wzx/Wzy-dependent pathways for the biosynthesis of secreted and capsular polysaccharides in Gram-negative bacteria, the polysaccharide co-polymerase (PCP) is a key protein that facilitates repeat unit polymerization and polysaccharide translocation across the outer membrane. PCP function depends on assembly/disassembly cycles that are determined by the phosphorylation/dephosphorylation cycles of an associated bacterial tyrosine kinase (BYK). Here, we identify the BY pseudokinase EcpK as essential for exopolysaccharide biosynthesis inMyxococcus xanthus. Based on experiments and computational structural biology, we suggest that EcpK is a scaffold protein, guiding the assembly/disassembly cycles of the partner PCPviabinding/unbinding cycles independently of Tyr phosphorylation/dephosphorylation cycles. We suggest that this novel mechanism is broadly conserved.
Epistasis in the receptor binding domain of contemporary H3N2 viruses that reverted to bind sialylated diLacNAc repeats
Authors: Liang Ruonan , Peccati Francesca , Ponse Niels L.D. , Uslu Elif , Boons Geert-Jan , Unione Luca , de Vries Robert P. 
Published: November 2024

AbstractSince the introduction of H3N2 influenza A viruses in the human population, these viruses have continuously evolved to escape human immunity, with mutations occurring in and around the receptor binding site. This process, called antigenic drift, recently resulted in viruses that recognize elongated glycans that are not abundantly displayed in the human respiratory tract. Such receptor specificities hampered our ability to pick and propagate vaccine strains. Using ELISA, glycan array, tissue staining, flow cytometry, and hemagglutinin assays, this study revealed that the most recent H3N2 viruses have expanded receptor specificity by regaining effective recognition to shorter glycans. In recent H3 strains, Y159 and T160 are responsible for restricted binding to elongated glycans; in contemporary strains, however, Y159N and T160I dominate with a consequent loss of strength in receptor binding. Yet, effective receptor interaction is rescued by a remote mutation in the 190-helix, Y195F. The results demonstrate epistasis of critical residues in three of the four structural elements composing the HA receptor-binding site (the 130-loop, 150-loop, and 190-helix), which synergistically contribute to shape receptor binding specificity. Interestingly, a positive correlation exists between binding to an asymmetrical N-glycan containing an α2,6 sialylated tri-LacNAc arm and binding to human and ferret respiratory tract tissues. Together, these results elucidate the epistatic nature of receptor binding specificity during influenza A virus H3N2 evolution.
Colour morphs as alternative solutions to the trade-off predicted by the Immuno-Competence Handicap Hypothesis
Authors: Sacchi Roberto , Coladonato Alan J. , Scali Stefano , Zuffi Marco A. L. , Palme Rupert , Mangiacotti Marco 
Published: November 2024

AbstractColour morphs in polymorphic species represent a suite of heritable traits controlled by separate sets of loci, which correspond to alternative peaks in the fitness surfaces. Pleiotropic effects of hormones have been hypothesized to be involved in the maintenance of morphs, but no experiments have been done to test it so far. In this study, we experimentally increased testosterone plasma levels in colour morph of the common wall lizards to test if white and yellow morphs follow two alternative strategies imposed by trade-off depicted in the Immuno-Competence Handicap Hypotheses. Yellow males invest in a more aggressive behaviour at the expense of a reduced immune function, whereas white males invest in greater survival at the expense of a reduced competitiveness. Plasma T levels were increased through transdermal administration. Before and after treatment, we measured i) the immune-response of lizards through phytohaemoagglutinin (PHA), and ii) the aggressive response by the introduction of a small mirror into the plastic enclosure to mimic the intrusion of a stranger male in its own territory. The hormone administration caused a higher immune-suppression in white than yellow males, and a switch to less aggressive behaviour against the mirrored image. Overall, increased plasma testosterone levels resulted in the disappearance of differences between morphs of both immune-response and aggressive behaviour. These results supplied experimental evidence of the existence of morph-specific strategies in common wall lizards depending on the investment in territorial aggression or in a longer survival, as alternative solutions to the trade-off predicted by the Immuno- Competence Handicap Hypothesis.