bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-existing Immunity to Influenza Aids Ferrets in Developing Stronger and Broader Vaccine-induced Antibody Responses
Authors: Ge Yang , Lu Yao , Allen James , Einav Tal , Nkaleke Dennis Iziogo , Bai Fengwei , Handel Andreas , Ross Ted , Shen Ye 
Published: February 2024

AbstractInfluenza seasons occur annually, building immune history for individuals, but the influence of this history on subsequent influenza vaccine protection remains unclear. We extracted data from an animal trial to study its potential impact. The trial involved 80 ferrets, each receiving either one type of infection or a placebo before vaccination. We quantified the vaccine protection by evaluating hemagglutination inhibition (HAI) antibody titer responses. We tested whether hosts with different infection histories exhibited similar level of responses when receiving the same vaccine for all homologous and heterologous outcomes. We observed that different pre-existing immunities were generally beneficial to vaccine induced responses, but varied in magnitude. Without pre-immunity, post-vaccination HAI titers after the 1st dose of the vaccine were less likely to be above 1:40, and a booster shot was needed. Our study suggests that pre-existing immunity may strengthen and extend the homologous and heterologous vaccine protection.
Perinatal ampicillin administration modulates murine bile acid metabolismin vivo- an observational study
Authors: Thomas Sydney P , Askarian Fatemeh , Kousha Armin , Suzuki Emi , Tsai Chih Ming , Liu George , Nizet Victor , Dorrestein Pieter C , Tsunoda Shirley M. 
Published: February 2024

AbstractAntibiotics are an indispensable tool of modern medicine, yet their impact extends beyond eliminating harmful bacteria to perturbing the commensal bacteria constituting the gut microbiome. This collateral damage is particularly significant in early life when the gut microbiome is still developing. In humans, antibiotic administration during infancy and childhood is associated with various long-term negative health outcomes. However, existing research has predominantly focused on the direct administration of antibiotics to infants, leaving uncertainties about whether indirect antibiotic exposure produces similar effects. Here, we use mouse models to investigate how three distinct routes of exposure to the commonly prescribed broad-spectrum antibiotic ampicillin influences parent and infant metabolism. These methods simulate major modes of both direct and indirect antibiotic exposure: intravenous antibiotic administration to the mother immediately before birth mimicking intrapartum antibiotic prophylaxis, antibiotic use by the mother during lactation, and direct administration to infants mimicking empiric antibiotic treatment for neonatal sepsis. Through untargeted metabolomics of fecal samples from mouse dams and infants, we identified one class of compounds, bile acids and related cholane steroids, as particularly sensitive to ampicillin treatment. Bile acids, produced by the host and extensively modified by the gut microbiome, serve as important mediators in the cross-talk between the microbiota and the host. Here, we detail the coordinated changes in bile acid metabolism in response to a commonly prescribed antibiotic, focusing on dams treated both pre- and postpartum. Additionally, we identify unique bile acids associated with weight gain in infant mice.ImportanceAntibiotics are widely used perinatally, administered to both parents and infants before, during, and after birth. While they can play a life-saving role, antibiotics also result in collateral damage to the beneficial microbes constituting the gut microbiome. These microbes have many important functions, particularly in the metabolism of small molecules in the body. One such group of molecules, bile acids, undergo extensive modifications by bacteria and may act as a “language” through which microbes communicate with the host. This observational study investigates the impact of the commonly prescribed antibiotic ampicillin on the metabolism of these molecules during childbirth. Our results indicate that ampicillin administration pre- or post-partum significantly alters the mother’s bile acid metabolism, but has a minimal influence on infant bile acid levels. However, in all cases, ampicillin administration significantly increased infant weight, even when the antibiotic was solely administered to the mother.
Phenomics Assistant: An Interface for LLM-based Biomedical Knowledge Graph Exploration
Authors: O’Neil Shawn T , Schaper Kevin , Elsarboukh Glass , Reese Justin T , Moxon Sierra A T , Harris Nomi L , Munoz-Torres Monica C , Robinson Peter N , Haendel Melissa A , Mungall Christopher J 
Published: February 2024

AbstractWe introduce Phenomics Assistant, a prototype chat-based interface for querying the Monarch knowledge graph (KG), a comprehensive biomedical database. While unaided Large Large Language models (LLMs) are prone to mistakes in factual recall, their strong abilities in summarization and tool use suggest new opportunities to help non-expert users query and interact with complex data, while drawing on the KG to improve reliability of the answers. Leveraging the ability of LLMs to interpret queries in natural language, Phenomics Assistant enables a wide range of users to interactively discover relationships between diseases, genes, and phenotypes.To assess the reliability of our approach and compare the accuracy of different LLMs, we evaluated Phenomics Assistant answers on benchmark tasks for gene-disease association and gene alias queries. While comparisons across tested LLMs revealed differences in their ability to interpret KG-provided information, we found that even basic KG access markedly boosts the reliability of standalone LLMs. By enabling users to pose queries in natural language and summarizing results in familiar terms, Phenomics Assistant represents a new approach for navigating the Monarch KG.
Mapping domains of early-life determinants of future multimorbidity across three UK longitudinal cohort studies
Authors: Stannard S , Berrington A , Fraser SDS , Paranjothy S , Hoyle RB , Owen RK , Akbari A , Shiranirad M , Chiovoloni R , Alwan NA 
Published: February 2024

AbstractMany studies use a reductionist approach to isolate the influence of one factor in childhood on multimorbidity rather than consider the combined effect of wider determinants. We explored how potential multiple early-life determinants of multimorbidity can be characterised across three UK cohort studies.We used the National Child Development Study (NCDS), the 1970 British Cohort Study (BCS70), and the Aberdeen Children of the 1950s Study (ACONF) to identified early-life variables that fit into 12 domains of early-life determinants of multimorbidity. Variables were assigned into 12 domains; principal component analysis reduced the dimensionality of the data and structured variables into subgroups.The data audit identified 7 domains in ACONF, 10 domains in NCDS and 12 domains in BCS70. Components included maternal fertility histories within the prenatal, antenatal and birth domain, long-term illnesses within the child health domain, educational ability within the child education and health literacy domain, ethnicity within the demography domain, parental health behaviours within the transgenerational domain, housing within the socioeconomic domain and parental-child interactions within the parental-family domain.Conceptualising the risk of future multimorbidity as lifecourse domains composed of multiple factors can help challenge the existing understanding of disease aetiology and develop new ideas for prevention of multimorbidity.
Mitigating Machine Learning Bias Between High Income and Low-Middle Income Countries for Enhanced Model Fairness and Generalizability
Authors: Yang Jenny , Clifton Lei , Dung Nguyen Thanh , Phong Nguyen Thanh , Yen Lam Minh , Xuan Thy Doan Bui , Soltan Andrew A. S. , Thwaites Louise , Clifton David A. 
Published: February 2024

AbstractCollaborative efforts in artificial intelligence (AI) are increasingly common between high-income countries (HICs) and low-to middle-income countries (LMICs). Given the resource limitations often encountered by LMICs, collaboration becomes crucial for pooling resources, expertise, and knowledge. Despite the apparent advantages, ensuring the fairness and equity of these collaborative models is essential, especially considering the distinct differences between LMIC and HIC hospitals. In this study, we show that collaborative AI approaches can lead to divergent performance outcomes across HIC and LMIC settings, particularly in the presence of data imbalances. Through a real-world COVID-19 screening case study, we demonstrate that implementing algorithmic-level bias mitigation methods significantly improves outcome fairness between HIC and LMIC sites while maintaining high diagnostic sensitivity. We compare our results against previous benchmarks, utilizing datasets from four independent United Kingdom Hospitals and one Vietnamese hospital, representing HIC and LMIC settings, respectively.
A web-based tool for real-time adequacy assessment of kidney biopsies
Authors: Ahangaran Meysam , Sun Emily , Le Khang , Sun Jiawei , Wang William M. , Tan Tian Herng , Burdine Lyle J. , Dvanajscak Zeljko , Cassol Clarissa A. , Sharma Shree , Kolachalama Vijaya B. 
Published: February 2024

AbstractThe escalating incidence of kidney biopsies providing insufficient tissue for diagnosis poses a dual challenge, straining the healthcare system and jeopardizing patients who may require re-biopsy or face the prospect of an inaccurate diagnosis due to an unsampled disease. Here, we introduce a web-based tool that can provide real-time, quantitative assessment of kidney biopsy adequacy directly from photographs taken with a smartphone camera. The software tool was developed using a deep learning-driven automated segmentation technique, trained on a dataset comprising nephropathologist-confirmed annotations of the kidney cortex on digital biopsy images. Our framework demonstrated favorable performance in segmenting the cortex via 5-fold cross-validation (Dice coefficient: 0.788±0.130) (n=100). Offering a bedside tool for kidney biopsy adequacy assessment has the potential to provide real-time guidance to the physicians performing medical kidney biopsies, reducing the necessity for re-biopsies. Our tool can be accessed through our web-based platform:http://www.biopsyadequacy.org.
Arsinothricin Biosynthesis Involving a Noncanonical Radical SAM Enzyme for C-As Bond Formation
Authors: Yao Yadi , He Jiale , Dong Min 
Published: February 2024

ABSTRACTArsinothricin is a potent antibiotic secreted by soil bacteria. The biosynthesis of Arsinothricin was proposed to involve two steps. The first step is C-As bond formation between trivalent As and the 3-amino-3-carboxypropyl (ACP) group of S-adenosyl-L-methionine (SAM), which is catalyzed by the protein ArsL. However, the reaction has not been verified in vitro, and ArsL has not been characterized in detail. Interestingly, ArsL contains a CxxxCxxC motif and thus belongs to the radical SAM enzyme superfamily, the members of which cleave SAM and generate a 5′-deoxyadenosyl radical. Here, we found that ArsL cleaves the Cγ,Met–S bond of SAM and generates an ACP radical that resembles Dph2, a noncanonical radical SAM enzyme involved in diphthamid biosynthesis. As Dph2 does not contain the CxxxCxxC motif, ArsL is a unique noncanonical radical SAM enzyme that contains this motif but generates an ACP radical. Together with the methyltransferase ArsM, we successfully reconstituted arsinothricin biosynthesis in vitro. ArsL has a conserved RCCLKC motif in the C-terminal sequence and belongs to the RCCLKC-tail radical SAM protein subfamily. By truncation, we showed that this motif binds to the substrate arsenite and is highly important for its activity. Our results suggested that ArsL is a noncanonical radical SAM enzyme with a canonical radical SAM enzyme motif, implying that more noncanonical radical SAM chemistry may exist within the radical SAM enzyme superfamily.TOC
Aging is associated with a modality-specific decline in taste
Authors: Brown Elizabeth B. , Lloyd Evan , Martin-Peña Alfonso , McFarlane Samuel , Dahanukar Anupama , Keene Alex C. 
Published: February 2024

ABSTRACTDeficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders, including Alzheimer’s Disease (AD). In many cases, chemosensory deficits are harbingers of neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into the fundamental dysfunction associated with aging and neurodegeneration. The fruit fly,Drosophila melanogaster, is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging and neurodegeneration on chemosensation remain largely unexplored in this model, particularly with respect to taste. To determine whether the effects of aging on taste are conserved in flies, we compared the response of flies to different appetitive tastants. Aging impaired response to sugars, but not medium-chain fatty acids that are sensed by a shared population of neurons, revealing modality-specific deficits in taste. Selective expression of the human amyloid beta (Aβ) 1-42 peptide bearing the Arctic mutation (E693E) associated with early onset AD in the neurons that sense sugars and fatty acids phenocopies the effects of aging, suggesting that the age-related decline in response is localized to gustatory neurons. Functional imaging of gustatory axon terminals revealed reduced response to sugar, but not fatty acids. Axonal innervation of the fly taste center was largely intact in aged flies, suggesting that reduced sucrose response does not derive from neurodegeneration. Conversely, expression of the amyloid peptide in sweet-sensing taste neurons resulted in reduced innervation of the primary fly taste center. A comparison of transcript expression within the sugar-sensing taste neurons revealed age-related changes in 66 genes, including a reduction in odorant-binding protein class genes that are also expressed in taste sensilla. Together, these findings suggest that deficits in taste detection may result from signaling pathway-specific changes, while different mechanisms underly taste deficits in aged and AD model flies. Overall, this work provides a model to examine cellular deficits in neural function associated with aging and AD.
Conformational plasticity of a BiP-GRP94 chaperone complex
Authors: Brenner Joel Cyrille , Zirden Linda , Almeida-Hernandez Yasser , Kaschani Farnusch , Kaiser Markus , Sanchez-Garcia Elsa , Poepsel Simon , Hellerschmied Doris 
Published: February 2024

AbstractHsp70/Hsp90-chaperones and their regulatory co-chaperones are critical for maintaining protein homeostasis. GRP94, the sole Hsp90-chaperone in the secretory pathway of mammalian cells, is essential for the maturation of important secretory and transmembrane proteins. Without the requirement of co-chaperones, the Hsp70-protein BiP controls regulatory conformational changes of GRP94 – the structural basis of which has remained elusive. Here, we biochemically and structurally characterize the formation of a BiP-GRP94 chaperone complex and its transition to a conformation expected to support the loading of substrate proteins from BiP onto GRP94. BiP initially binds to the open GRP94 dimer via an interaction interface that is conserved among Hsp70/90 paralogs. Subsequently, binding of a second BiP protein stabilizes a semi-closed GRP94 dimer, thereby advancing the chaperone cycle. Our findings highlight a fundamental mechanism of direct Hsp70/90 cooperation, independent of co-chaperones.
DrosophilaFog/Cta and T48 pathways have overlapping and distinct contributions to mesoderm invagination
Authors: Horo Uzuki , Clarke Nat , Martin Adam C. 
Published: February 2024

AbstractThe regulation of the cytoskeleton by multiple pathways, sometimes in parallel, is a common principle of morphogenesis. A classic example of regulation by parallel pathways isDrosophilagastrulation, where the inputs from the Folded gastrulation (Fog)/Concertina (Cta) and the T48 pathways induce apical constriction and mesoderm invagination. Whether there are distinct roles for these separate pathways in regulating the complex spatial and temporal patterns of cytoskeletal activity that accompany early embryo development is still poorly understood. We investigated the roles of the Fog/Cta and T48 pathways and found that, by themselves, the Cta and T48 pathways both promote timely mesoderm invagination and apical myosin II accumulation, with Cta being required for timely cell shape change ahead of mitotic cell division. We also identified distinct functions of T48 and Cta in regulating cellularization and the uniformity of the apical myosin II network, respectively. Our results demonstrate that both redundant and distinct functions for the Fog/Cta and T48 pathways exist.
Identification and characterization of a temperature sensitive chlorotic soybean mutant
Authors: Hancock C. Nathan , Germany Tetandianocee , Redd Priscilla , Timmons Jack , Lipford Jeffery , Burns Samantha , Cervantes-Perez Sergio Alan , Libault Marc , Shen Wenhao , An Yong-qiang Charles , Kanizay Lisa , Yerka Melinda , Parrott Wayne A. 
Published: February 2024

AbstractScreening a transposon-mutagenized soybean population led to the discovery of a recessively inherited chlorotic phenotype. This “vir1” phenotype results in smaller stature, weaker stems, and a smaller root system with smaller nodules. Genome sequencing identified 15 candidate genes with mutations likely to result in a loss of function. Amplicon sequencing of a segregating population was then used to narrow the list to a single candidate mutation, a single-base change inGlyma.07G102300that disrupts splicing of the second intron. Single cell transcriptomic profiling indicates that this gene is expressed primarily in mesophyll cells and RNA sequencing data indicates it is upregulated in germinating seedlings by cold stress. Previous studies have shown that mutations toOs05g34040, the rice homolog ofGlyma.07G102300, produced a chlorotic phenotype that was more pronounced in cool temperatures. Growing soybean vir1 mutants at lower temperatures also resulted in a more severe phenotype. In addition, transgenic expression of wild typeGlyma.07G102300in the knockout mutant of the Arabidopsis homologAt4930720rescues the chlorotic phenotype, further supporting the hypothesis that the mutation inGlyma.07G102300is causal of the vir1 phenotype.
Translational T-box riboswitches bind tRNA by modulating conformational flexibility
Authors: Campos-Chavez Eduardo , Paul Sneha , Zhou Zunwu , Alonso Dulce , Verma Anjali R. , Fei Jingyi , Mondragón Alfonso 
Published: February 2024

AbstractT-box riboswitches, paradigmatic non-coding RNA elements involved in genetic regulation in most Gram-positive bacteria, are adept at monitoring amino acid metabolism through direct interactions with specific tRNAs. T-box riboswitches assess tRNA aminoacylation status, subsequently regulating the transcription or translation of downstream genes involved in amino acid metabolism. Here we present single-molecule FRET studies of theMycobacterium tuberculosis IleST-box riboswitch, a model of T-box translational regulation. The data supports a two-step binding model where the tRNA anticodon is recognized first, followed by interactions with the NCCA sequence. Specifically, after anticodon recognition, tRNA in the partially bound state can transiently dock into the discriminator domain, resembling the fully bound state, even in the absence of the tRNA NCCA-discriminator interactions. Establishment of the NCCA-discriminator interactions significantly stabilizes the fully bound state. Collectively, the data suggests higher conformational flexibility in translation-regulating T-box riboswitches, compared to transcription-regulating ones, and supports a conformational selection model for NCCA recognition. Furthermore, it was found that the conserved RAG sequence is pivotal in maintaining specific interactions with the tRNA NCCA sequence by preventing sampling of an aberrant conformational state, while Stem IIA/B-linker interactions impact the conformational dynamics and the stability of both the partially bound and fully bound states. The present study provides a critical kinetic basis for how specific sequences and structural elements in T-box riboswitches enable the binding efficiency and specificity required to achieve gene regulation.
Tyrosine-sulfated peptide hormone induces flavonol biosynthesis to control elongation and differentiation in Arabidopsis primary root
Authors: Ercoli Maria Florencia , Shigenaga Alexandra M. , Teixeira de Araujo Artur , Jain Rashmi , Ronald Pamela C. 
Published: February 2024

AbstractIn Arabidopsis roots, growth initiation and cessation are organized into distinct zones. How regulatory mechanisms are integrated to coordinate these processes and maintain proper growth progression over time is not well understood. Here, we demonstrate that the peptide hormone PLANT PEPTIDE CONTAINING SULFATED TYROSINE 1 (PSY1) promotes root growth by controlling cell elongation. Higher levels of PSY1 lead to longer differentiated cells with a shootward displacement of characteristics common to mature cells. PSY1 activates genes involved in the biosynthesis of flavonols, a group of plant-specific secondary metabolites. Using genetic and chemical approaches, we show that flavonols are required for PSY1 function. Flavonol accumulation downstream of PSY1 occurs in the differentiation zone, where PSY1 also reduces auxin and reactive oxygen species (ROS) activity. These findings support a model where PSY1 signals the developmental-specific accumulation of secondary metabolites to regulate the extent of cell elongation and the overall progression to maturation.TeaserPSY1-induced flavonol biosynthesis in Arabidopsis roots modulates the distance from the root tip at which cell elongation ceases.
Quantum-inspired computing technology in operations and logistics management
Authors: Núñez-Merino Miguel , Maqueira-Marín Juan Manuel , Moyano-Fuentes José , Castaño-Moraga Carlos Alberto 
Published: February 2024

PurposeThe purpose of this paper is to explore and disseminate knowledge about quantum-inspired computing technology's potential to solve complex challenges faced by the operational agility capability in Industry 4.0 manufacturing and logistics operations.Design/methodology/approachA multi-case study approach is used to determine the impact of quantum-inspired computing technology in manufacturing and logistics processes from the supplier perspective. A literature review provides the basis for a framework to identify a set of flexibility and agility operational capabilities enabled by Industry 4.0 Information and Digital Technologies. The use cases are analyzed in depth, first individually and then jointly.FindingsStudy results suggest that quantum-inspired computing technology has the potential to harness and boost companies' operational flexibility to enhance operational agility in manufacturing and logistics operations management, particularly in the Industry 4.0 context. An exploratory model is proposed to explain the relationships between quantum-inspired computing technology and the deployment of operational agility capabilities.Originality/valueThis is study explores the use of quantum-inspired computing technology in Industry 4.0 operations management and contributes to understanding its potential to enable operational agility capability in manufacturing and logistics operations.