bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bat Influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
Authors: Osman Maria Kaukab , Robert Jonathan , Broich Lukas , Frank Dennis , Grosse Robert , Schwemmle Martin , Wrobel Antoni , Ciminski Kevin , Sieben Christian , Reuther Peter 
Published: July 2024

AbstractPrior to the discovery of the bat influenza A virus (IAV) subtypes H17N10 and H18N11, it was believed that all IAVs bind via the viral hemagglutinin (HA) to sialic acid residues to mediate attachment and subsequent viral entry. Both HA subtypes, H17 and H18, however, do not bind to sialic acids but instead engage a proteinaceous receptor: major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Since conventional IAVs require attachment to clusters of sialylated glycans to overcome the low affinity of the HA-sialic acid interaction, we hypothesized that bat HA would likewise interact with multiple MHCII molecules. Here, we used photoactivated localization microscopy (PALM) on fixed and live cells expressing MHCII fused to appropriate fluorescent reporters. We show that bat IAV particles attach to pre-existing MHCII clusters present on susceptible cells and that the local HA-MHCII interaction results in an increased cluster size. To measure the impact of viral attachment on the dynamics of MHCII, we utilized an experimental setup designated “inverse infection” where intact viral particles were immobilized on coverslips before live MHCII-expressing cells were seeded on top. Recording the trajectories of single MHCII molecules, this approach revealed that the mobility of MHCII was indeed slowed down in viral proximity leading to a local enrichment of MHCII molecules beneath the viral particle. Taken together, these data suggest that attachment of viral particles leads to clustering of MHCII, a process similar to the MHCII dynamics observed during the formation of an immunological synapse.
Mechanisms of life cycle simplification in African trypanosomes
Authors: Oldrieve Guy R , Venter Frank , Cayla Mathieu , Verney Mylene , Hébert Laurent , Geerts Manon , Reet Nick Van , Matthews Keith R 
Published: July 2024

AbstractAfrican trypanosomes are important parasites in sub-Saharan Africa that undergo a quorum-sensing dependent development to morphologically stumpy forms in mammalian hosts to favour disease transmission by tsetse flies1. However, some trypanosome lineages have simplified their lifecycle by escaping dependence on tsetse allowing an expanded geographical range, with direct transmission between hosts achieved via biting flies and vampire bats (Trypanosoma brucei evansi, causing the disease ‘surra’) or through sexual transmission (Trypanosoma brucei equiperdum, causing ‘dourine’). Concomitantly, stumpy formation is reduced or lost, and the isolates are described as monomorphic, with infections spread widely in Africa, Asia, South America and parts of Europe. Here, using genomic analysis of distinct field isolates, we identified and functionally confirmed molecular changes that accompany the loss of the stumpy transmission stage in monomorphic clades. Further, using laboratory selection for resistance to the parasite’s quorum-sensing signal, we identified reversible steps in the initial development of monomorphism. This study identifies a trajectory of events that simplify the life cycle in emergent and established monomorphic trypanosomes, with impact on disease spread, vector control strategies, geographical range and virulence.
Cohesin-mediated 3D contacts tune enhancer-promoter regulation
Authors: Guckelberger Philine , Doughty Benjamin R. , Munson Glen , Rao Suhas S. P. , Tan Yingxuan , Cai Xiangmeng Shawn , Fulco Charles P. , Nasser Joseph , Mualim Kristy S. , Bergman Drew T. , Ray Judhajeet , Jagoda Evelyn , Munger Chad J. , Gschwind Andreas R. , Sheth Maya U. , Tan Anthony S. , Pulido Saul Godinez , Mitra Namita , Weisz David , Shamim Muhammad Saad , Durand Neva C. , Mahajan Ragini , Khan Ruqayya , Steinmetz Lars M. , Kanemaki Masato T. , Lander Eric S. , Meissner Alexander , Aiden Erez Lieberman , Engreitz Jesse M. 
Published: July 2024

AbstractEnhancers are key drivers of gene regulation thought to act via 3D physical interactions with the promoters of their target genes. However, genome-wide depletions of architectural proteins such as cohesin result in only limited changes in gene expression, despite a loss of contact domains and loops. Consequently, the role of cohesin and 3D contacts in enhancer function remains debated. Here, we developed CRISPRi of regulatory elements upon degron operation (CRUDO), a novel approach to measure how changes in contact frequency impact enhancer effects on target genes by perturbing enhancers with CRISPRi and measuring gene expression in the presence or absence of cohesin. We systematically perturbed all 1,039 candidate enhancers near five cohesin-dependent genes and identified 34 enhancer-gene regulatory interactions. Of 26 regulatory interactions with sufficient statistical power to evaluate cohesin dependence, 18 show cohesin-dependent effects. A decrease in enhancer-promoter contact frequency upon removal of cohesin is frequently accompanied by a decrease in the regulatory effect of the enhancer on gene expression, consistent with a contact-based model for enhancer function. However, changes in contact frequency and regulatory effects on gene expression vary as a function of distance, with distal enhancers (e.g., >50Kb) experiencing much larger changes than proximal ones (e.g., <50Kb). Because most enhancers are located close to their target genes, these observations can explain how only a small subset of genes — those with strong distal enhancers — are sensitive to cohesin. Together, our results illuminate how 3D contacts, influenced by both cohesin and genomic distance, tune enhancer effects on gene expression.
Integrative LC-MS and GC-MS Metabolic Profiling Unveils Dynamic Changes during Barley Malting
Authors: Rani Heena , Whitcomb Sarah J 
Published: July 2024

ABSTRACTMalting, a crucial process for beer production, involves complex biochemical transformations affecting sensory attributes and product quality. Despite extensive research on storage carbohydrates and proteins involved in malting, a detailed understanding of metabolic alterations during this process remains elusive, limiting our ability to assess and enhance malt quality. Our study employed untargeted GC-MS and LC-MS metabolite profiling to elucidate these changes across six malting stages: dry seed, post-steeping (DOG0), germination (DOG1, DOG3, DOG5), and kilning. We identified a total of 4980 known metabolites, with approximately 82% exhibiting significant changes. Statistical analysis revealed stage-dependent metabolic shifts, with most significant shifts occurring from DOG1 to DOG3 and during kilning. Dynamic changes in various chemical classes and metabolic pathways provide insights into processes critical for malt quality and beer production. Additionally, metabolites associated with antimicrobial properties and stress responses were identified, underscoring the interplay between barley and microbial metabolic processes during malting.HighlightsGC-MS and LC-MS profiling were performed to track metabolic changes during malting.Identified 4980 known compounds belonging to 346 chemical classes during malting.Many microbial metabolites demonstrated increased abundance in finished malt.The most significant metabolic shifts occurred during early germination and kilning.
An energy coupling factor transporter ofStreptococcus sanguinisimpacts antibiotic susceptibility as well as metal and membrane homeostasis
Authors: Rudzite Marta , O’Toole G. A. 
Published: July 2024

AbstractStreptococcus sanguinisis a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections.S. sanguiniscompetitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes toS. sanguinisantibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.ImportanceProficiency in micronutrient uptake is key for pathogen success in bacteria-bacteria and bacteria-host interactions within the infection context. Micronutrient uptake mechanisms are of interest in furthering the understanding of bacterial physiology within infection niche and as targets for design of antimicrobials. Here we describe how a deletion of a nutrient uptake transporter inS. sanguinisalters bacterial sensitivity to antibiotics. We also show that a defect in this candidate nutrient uptake system has consequences on the intracellular metal content, and also results in changes in membrane fatty acid composition and fluidity. This study demonstrates how disruption of a single nutrient uptake system disrupts bacterial physiology resulting in increased antibiotic sensitivity.
Synergistic reinforcement learning by cooperation of the cerebellum and basal ganglia
Authors: Yoshida Tatsumi , Sugino Hikaru , Yamamoto Hinako , Tanno Sho , Tamura Mikihide , Igarashi Jun , Isomura Yoshikazu , Hira Riichiro 
Published: July 2024

AbstractThe cerebral cortex, cerebellum, and basal ganglia are crucial for flexible learning in mammals. Recent studies suggest that reinforcement learning might occur in both the basal ganglia and cerebellum, as cerebellar climbing fibers represent reward prediction error. If the same learning mechanism via reward prediction error occurs simultaneously, it remains unclear how these two regions co-function. Here, we recorded neuronal activity in the output of cerebellum and basal ganglia, the cerebellar nuclei (CN) and substantia nigra pars reticulata (SNr), respectively, from ChR2 transgenic rats with high-density Neuropixels probes while optogenetically stimulating the cerebral cortex. The temporal response patterns could be categorized into two classes in both CN and SNr. Among them, the fast excitatory response of the CN due to the input of mossy fibers and the inhibitory response of the SNr via the direct pathway were synchronized. To further investigate this significance, we constructed a spiking network simulation based on connectome data and a reservoir model that mimics the experimental results. In the reservoir model, plasticity of both cerebellum and basal ganglia was essential for successful learning. Learning was impeded when cerebellar or basal ganglia output timing deviated by 10 ms from real data. Notably, the addition of β-oscillation to the cerebral cortex enhanced learning. These results indicate that coordinated output of the cerebellum and basal ganglia, with input from the cerebral cortex in a narrow frequency band, facilitates brain-wide synergistic reinforcement learning.Significance StatementThe cerebral cortex, cerebellum, and basal ganglia support learning. Recent research suggests that both the basal ganglia and cerebellum use a similar learning process called reinforcement learning, which involves predicting rewards. To understand how these brain regions work together, we recorded brain activity in rats while photo-stimulating the cerebral cortex. We found that two types of responses in the cerebellum and basal ganglia were synchronized, which might help activate the cerebral cortex. A computer model showed that precise timing of signals from both the cerebellum and basal ganglia is important for learning. This timing was important only when the cerebral cortex worked in a specific frequency range. Our findings suggest that coordinated brain activity enhances learning.
The neonatal Fc receptor and DPP4 are human astrovirus receptors
Authors: Ingle Harshad , Molleston Jerome M. , Hall Paige D. , Bui Duyen , Wang Leran , Foster Lynne , Antia Avan , Ding Siyuan , Lee Sanghyun , Fremont Daved H. , Baldridge Megan T. 
Published: July 2024

AbstractHuman astroviruses (HAstV) are major global causes of gastroenteritis, but little is known about host factors required for their cellular entry. Here, we utilized complementary CRISPR-Cas9-based knockout and activation screening approaches and identified neonatal Fc receptor (FcRn) and dipeptidyl-peptidase IV (DPP4) as entry factors for HAstV infection of human intestinal epithelial cells. Disruption of FcRn or DPP4 reduced HAstV infection in permissive cells and, reciprocally, overexpression of these factors in non-permissive cells was sufficient to promote infection. We observed direct binding between FcRn and HAstV virions as well as purified spike protein. Finally, inhibitors for DPP4 and FcRn currently in clinical use prevent HAstV infection in cell lines and primary human enteroids. Thus, our results reveal mechanisms of HAstV entry as well as druggable targets.One-Sentence SummaryTargeting FcRn or DPP4 using available therapies effectively prevents human astrovirus infection in human enteroid cultures.
Identification of stable reference genes for quantitative real-time PCR in human fibroblasts from lymph nodes and synovium
Authors: Rasouli S. , van Ansenwoude C.M.J. , Semmelink J.F. , van Baarsen L.G.M. , de Jong T.A. 
Published: July 2024

AbstractReal-time quantitative PCR (RT–qPCR) has emerged as an accurate and widely used technique for measuring gene expression levels. However, its reliability depends on the selection of appropriate reference genes to normalize for sample input. Accordingly, the identification of reference genes characterized by stable expression in cells and conditions of interest is essential for ensuring accurate expression values. To date, no study has specifically identified suitable reference genes for primary human cultured fibroblast-like synoviocytes (FLS) and lymph node stromal cells (LNSCs) within the context of rheumatoid arthritis (RA). These stromal cells play a critical role in the pathogenesis of disease. In this study, we evaluated the suitability of 15 candidate reference genes for normalizing transcript expression in FLS and LNSCs subjected to various in vitro stimuli. We included traditional reference genes often used for transcript normalization in fibroblasts as well as candidate genes identified as suitable reference genes via GeneVestigator analysis of publicly available transcriptomic data. RefFinder algorithms were used to identify the most stable reference genes for transcript normalization across the cell types and different experimental conditions. We determined that the optimal number of reference genes for every experimental condition tested was two;RPLP0andPOLR2Gexhibited the greatest stability across different experimental conditions for LNSCs. However, for FLS, we observed greater variability in the most stable reference genes across different experimental conditions. AlthoughPOLR2GandTBPemerged as the most stable reference genes under unstimulated conditions, our findings indicated that FLS require distinct reference genes for transcript normalization depending on the specific experimental conditions. Validation of the selected reference genes for normalizing the expression levels of metabolic genes in unstimulated FLS emphasized the importance of prior evaluation of potential reference genes, as arbitrary selection of reference genes could lead to data misinterpretation. This study constitutes the first systematic analysis for selecting optimal reference genes for transcript normalization in different types of human fibroblasts. Our findings emphasize the importance of proper selection of reference genes for each experimental condition separately when applying standard quantitative PCR technology for assessing gene expression levels.
Cryo-ET reveals thein situarchitecture of the polar tube invasion apparatus from microsporidian parasites
Authors: Usmani Mahrukh , Coudray Nicolas , Riggi Margot , Raghu Rishwanth , Ramchandani Harshita , Bobe Daija , Kopylov Mykhailo , Zhong Ellen D. , Iwasa Janet H. , Ekiert Damian C. , Bhabha Gira 
Published: July 2024

AbstractMicrosporidia are divergent fungal pathogens that employ a harpoon-like apparatus called the polar tube (PT) to invade host cells. The PT architecture and its association with neighboring organelles remain poorly understood. Here, we use cryo-electron tomography to investigate the structural cell biology of the PT in dormant spores from the human-infecting microsporidian species,Encephalitozoon intestinalis. Segmentation and subtomogram averaging of the PT reveal at least four layers: two protein-based layers surrounded by a membrane, and filled with a dense core. Regularly spaced protein filaments form the structural skeleton of the PT. Combining cryo-electron tomography with cellular modeling, we propose a model for the 3-dimensional organization of the polaroplast, an organelle that is continuous with the membrane layer that envelops the PT. Our results reveal the ultrastructure of the microsporidian invasion apparatusin situ, laying the foundation for understanding infection mechanisms.
Modified Chlorophyll Pigment at ChlD1Tunes Photosystem II Beyond the Red-Light Limit
Authors: Allgöwer Friederike , Sirohiwal Abhishek , Gamiz-Hernandez Ana P. , Pöverlein Maximilian C. , Fantuzzi Andrea , Rutherford A. William , Kaila Ville R. I. 
Published: July 2024

ABSTRACTPhotosystem II (PSII) is powered by the light-capturing properties of chlorophyllapigments that define the spectral range of oxygenic photosynthesis. Some photosynthetic cyanobacteria can acclimate to growth in longer wavelength light by replacing five chlorophylls for long wavelength pigments in specific locations, including one in the reaction center (RC). However, the exact location and the nature of this long wavelength pigment still remain uncertain. Here we have addressed the color-tuning mechanism of the farred light PSII (FRL-PSII) by excited state calculations at both theab initiocorrelated (ADC2) and linear-response time-dependent density functional theory (LR-TDDFT) levels in combination with large-scale hybrid quantum/classical (QM/MM) simulations and atomistic molecular dynamics. We show that substitution of a single chlorophyll pigment (ChlD1) at the RC by chlorophylldleads to a spectral shift beyond the far-red light limit, as a result of the protein electrostatic, polarization and electronic coupling effects that reproduce key structural and spectroscopic observations. Pigment substitution at the ChlD1site further results in a low site energy within the RC that could function as a sink for the excitation energy and initiate the primary charge separation reaction, driving the water oxidation. Our findings provide a basis for understanding color-tuning mechanisms and bioenergetic principles of oxygenic photosynthesis at the far-red light limit.
IFRS-9, expected loan loss provisioning and bank liquidity creation: early evidence
Authors: Ghosh Saibal 
Published: July 2024

Purpose
The relevance of both microeconomic and macroeconomic factors in driving banks’ liquidity creation within a cross-country setup has been addressed in prior research. The purpose of this study is to explore whether and how the recent International Financial Reporting Standards-9 (IFRS-9) accounting standards affect this relationship.

Design/methodology/approach
The author exploits the staggered implementation of IFRS-9 across countries and use a difference-in-differences framework to tease out the causal impact.

Findings
The findings indicate that the enactment of IFRS-9 leads to an increase in asset-side liquidity creation and a decline of broadly similar magnitude in liability-side liquidity creation. As a result, total liquidity creation remains unaltered. Disaggregatedly, the evidence shows that all the key channels on the asset and liability side are instrumental in explaining this behaviour.

Originality/value
The author views this as one of the early studies in a cross-country setup to explore the interlinkage between IFRS-9 and bank liquidity creation. Since liquidity creation measure provides a comprehensive metric of liquidity supplied by banks to the market, the study seeks to inform the policy debate on the role of these recently instituted accounting standards on bank liquidity behaviour.
Information behavior of weaver community in Varanasi: an analytical study
Authors: Ansari Mohd Shoaib , Tripathi Aditya 
Published: July 2024

Purpose
This study aims to evaluate the information behavior of the Banarasi Sarees weaving community and propose an information-focused policy tailored to their needs.

Design/methodology/approach
This study was conducted in seven weaver-centered areas in Varanasi and was designed around semi-structured interviews to explore various information-related aspects among the weavers. It aims to focus on their knowledge of weaving, their information needs, seeking behavior, preferred communication channels, prioritization of information and methods for enhancing information-related situations.

Findings
It was found that a lack of information among weavers significantly impacts their livelihoods and businesses. They struggle to make product, pricing and marketing decisions without access to accurate, timely and relevant information. They cannot expand their businesses and invest in new equipment and materials. The weavers need a library with a specialized collection and a qualified librarian to guide them in using the information sources. They also need a dedicated information system and community information centers to provide better information services.

Originality/value
This study is a work whose expected results and findings would help policymakers adopt measures to encourage providing information services through public libraries and community information centers. The results of this study may be further used to frame information policy for weavers and other occupational communities.