bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural elucidation of the haptoglobin–hemoglobin clearance mechanism by macrophage scavenger receptor CD163
Authors: Huang Ching-Shin , Wang Hui , White Joshua B. R. , Degtjarik Oksana , Huynh Cindy , Brannstrom Kristoffer , Horn Mark T. , Muench Stephen P. , Somers Will S. , Chaparro-Riggers Javier , Lin Laura , Mosyak Lidia 
Published: February 2025

AbstractIntravascular hemolysis releases hemoglobin into the bloodstream, which can damage vascular and renal tissues due to its oxidative nature. Circulating haptoglobin acts as a primary defense by binding to free hemoglobin, forming a haptoglobin-hemoglobin (HpHb) complex that is then recognized and cleared by the CD163 scavenger receptor on macrophages. While the function and structure of HpHb complex are mostly well-defined, the molecular mechanism underlying its interaction with CD163 remains unclear. Here we report the cryo-electron microscopy structures of CD163 in its unliganded state and in its complex with HpHb. These structures reveal that CD163 functions as a trimer, forming a composite binding site at its center for one protomer of the dimeric HpHb, resulting in a 3:1 binding stoichiometry. In the unliganded state, CD163 can also form a trimer, but in an autoinhibitory configuration that occludes the ligand binding site. Widespread electrostatic interactions mediated by calcium ions are pivotal in both pre-ligand and ligand-bound receptor assemblies. This calcium-dependent mechanism enables CD163/HpHb complexes to assemble and, once internalized, disassemble into individual components upon reaching the endosome, where low calcium and lower pH conditions prevail. Collectively, this study elucidates the molecular mechanism by which CD163-mediated endocytosis efficiently clears different isoforms of HpHb.
Mediator-29 LimitsCaenorhabditis elegansFecundity
Authors: Fan Qi , Tran Christopher , Cao Wei , Pocock Roger 
Published: February 2025

ABSTRACTMediator is an evolutionarily conserved multiprotein complex that acts as a critical coregulator of RNA polymerase II-mediated transcription. While core Mediator components are broadly required for transcription, others govern specific regulatory modules and signalling pathways. Here, we investigated the function of MDT-29/MED29 in theCaenorhabditis elegansgerm line. We found that endogenously-tagged MDT-29 is ubiquitously expressed and concentrated in discrete foci within germ cell nuclei. Functionally, depleting MDT-29 in the germ line during larval development boosted fecundity. We determined that the increase in progeny production was likely caused by a combination of an expanded germline stem cell pool and decreased germ cell apoptosis. Thus, MDT-29 may act to optimize specific gene expression programs to control distinct germ cell behaviors, providing flexibility to progeny production in certain environments.
An image-based biophysical model of the lung to investigate the effect of pulmonary surfactant on lung function
Authors: Neelakantan Sunder , Myers Kyle J. , Rizi Rahim , Smith Bradford J. , Avazmohammadi Reza 
Published: February 2025

ABSTRACTLung biomechanics aims to understand the structure-function relationship in the lung under normal and pathological conditions. Pulmonary surfactant has a key structural role in lung function with a significant contribution to the mechanical response of the lungs during respiration. Pulmonary surfactant dynamically regulates surface tension at the air-liquid interface to decrease stiffness during respiration and prevent alveolar collapse during lower volumes. Many lung injuries involve alterations to the contribution of surfactants to lung function. We developed a novel biophysical model using a poroelastic formulation that incorporates pulmonary surfactant dynamics and aims to quantify the contribution of the pulmonary surfactant toward lung compliance. The effect of pulmonary surfactant was modeled as a surface energy function, and the surface behavior was converted to bulk behavior by assuming uniform spherical alveoli. The model was used to simulate respiration and investigate the effect of altered surface tension caused by surfactant dysfunction. The model captured the characteristic sigmoidal inspiratory pressure-volume curve and hysteresis observed during clinical measurements. In addition, the model predicted the expected behavior in surfactant dysfunction in lung injuries. We expect this work to serve as an essential step towards de-convoluting and predicting the contributions of the lung parenchyma and pulmonary surfactant to global and regional lung compliance in health and disease.
Immunological surveillance using gSG6-P1 biomarker reveals spatio-temporal dynamics ofAnophelesexposure and gaps in malaria risk assessment
Authors: Saeung Manop , Jupatanakul Natapong , Jampeesri Niramon , Afelt Aneta , Chareonviriyaphap Theeraphap , Manguin Sylvie 
Published: February 2025

AbstractMalaria risk assessment often relies on the entomological inoculation rate (EIR), which quantifies infectious bites per person over time. However, this approach does not account for human behavioral variability, limiting its effectiveness in accurately reflecting malaria risk at the population level. Recent studies have attempted to estimate mosquito-bite risk through the measurement of antibody responses toAnophelessalivary peptides. However, this approach has yet to be applied to evaluate malaria transmission risks along the Thailand-Cambodia border. This study aims to employ an immune biomarker forAnophelessalivary peptide (anti-gSG6-P1) to identify key risk factors associated with exposure toAnophelesmosquitoes in Sisaket Province, a region bordering Thailand and Cambodia. Blood samples from the same set of 184 participants were collected via finger prick during each season: rainy (August 2022), cool-dry (December 2022), and hot-dry (April 2023). Anti-gSG6-P1 antibody levels were quantified using enzyme-linked immunosorbent assay (ELISA). Factor Analysis of Mixed Data (FAMD) revealed that seasonality exerts the strongest influence on antibody levels. This pattern was likely driven by human activities, particularly the frequency of rubber tapping activity in the rubber plantation area whereAnophelesspecies, especiallyAnopheles dirus,are present. While this study successfully identifies seasonality and human factors as critical influences on antibody responses, it also highlights gaps in understanding the kinetics of anti-salivary peptide responses toAnophelesbites, particularly in species with low salivary peptides sequence similarity to that ofAnopheles gambiae. These findings emphasize the need for the development of new serological tools tailored to malaria vectors in the Greater Mekong Subregion to enhance malaria risk assessment and improve vector control strategies.
Automated IntraVascular UltraSound Image Processing and Quantification of Coronary Artery Anomalies: The AIVUS-CAA software
Authors: Stark Anselm W. , Mohammadi Kazaj Pooya , Balzer Sebastian , Ilic Marc , Bergamin Manuel , Kakizaki Ryota , Giannopoulos Andreas , Haeberlin Andreas , Räber Lorenz , Shiri Isaac , Gräni Christoph 
Published: February 2025

AbstractBackgroundCoronary artery anomalies (CAA) with an intramural course are associated with elevated risks of ischemia and sudden cardiac death under stress. Intravascular ultrasound (IVUS) is essential for assessing coronary vessel dynamics in these patients. However, the rarity of such anomalies, along with unique geometric changes in the intramural course and ostium, complicates image analysis, leading to inconsistencies and time-consuming evaluations. Our developed executable, zero/low-code software addresses these limitations by providing automated lumen segmentation and cardiac phase identification in IVUS images acquired during rest and stress protocols.MethodsThe software includes: (1) Automated segmentation of lumen contours trained and validated on 6713 frames (developed by using human in the loop active learning process) and tested on 914 frames, IVUS frames from fifteen patients (22 studies) with right CAA using a modified U2-Net deep learning (DL) model; (2) Extraction of systolic and diastolic frames via a dual-gating approach combining image- and contour-based methods; and (3) A graphical user interface enabling manual correction of the results. The gating module was validated using a custom flow-loop simulating patient-specific hemodynamics, while segmentation accuracy was assessed via intra-class correlation coefficient (ICC) analysis comparing AI-generated contours with those delineated by experienced readers.ResultsThe DL model achieved a mean Dice score of 0.86 (SD: 0.07), sensitivity of 0.87 (SD: 0.11), and specificity of 0.98 (SD: 0.01) on the test set. ICC values for lumen area measurements were 0.92 (95%CI: 0.88-0.95) for rest and 0.98 (95%CI: 0.97-0.99) for stress conditions (allp <0.001). The gating module demonstrated excellent reproducibility for identifying systolic and diastolic frames under both conditions (ICC = 1.00,p <0.001).ConclusionsAIVUS-CAA offers a reliable, automated tool for precise IVUS analysis at rest and during stress, enhancing the evaluation of geometrical changes of coronary vessels in CAA patients and enabling efficient clinical decision-making in a streamlined workflow.Graphical AbstractHighlightsDeveloped the first automated software (AIVUS-CAA) specifically designed to quantify dynamic geometric changes in coronary artery anomalies, addressing a critical gap in analyzing intramural coronary segments.Introduced a novel dual-gating algorithm combining image-based and contour-derived signals to identify systolic/diastolic phases, validated under both rest and simulated exercise conditions – a first for stress IVUS analysis in CAA.
Year-round rhythms: alpine plant species modulate soil and microbial dynamics during the growing season and under the snow
Authors: Ruka Adam Taylor , Schweichhart Johannes , Dolezal Jiri , Čapková Kateřina , Chlumská Zuzana , Calvillo-Medina Rosa Paulina , Meador Travis B. , Praeg Nadine , Illmer Paul , Angel Roey , Rehakova Klara 
Published: February 2025

AbstractSoil-plant-microbe interactions are integral throughout most terrestrial ecosystems, yet the importance of plant phenology and seasonal dynamism upon these relationships remains unknown. Given the pronounced seasonality of alpine environments, we sampled 8 plant species occurring in two habitats (alpine meadow and subnival zone) across four seasons (including snow-covered winter) in the Central Eastern Alps to determine the plant growth strategies and plant nutrient parameters which closely couple with rhizosphere microbial parameters.In subnival locations, plants exhibited stronger seasonal changes among leaf and root tissue nutrient concentrations and non-structural carbohydrates (NSCs) compared to those in lower elevation alpine meadows. However, rhizosphere microbial parameters (microbial biomass (MBC), extracellular enzymes, and community composition) demonstrated more seasonal changes in the alpine meadow locations.A phenological delay was observed in bacterial and fungal communities of the subnival zone, with peak plant rhizosphere differentiation occurring later in the season than in alpine meadows. Therefore, the prolonged cold conditions and shorter growing season in higher elevations likely add a temporal aspect to the commonly used elevational gradient approach, which is not often considered.MBC and enzymatic potential within the rhizosphere were high across all plant species in the alpine meadow during the winter sampling, despite notable differences in microbial community composition. In contrast, winter rhizosphere communities did not differ between plant species in subnival locations, although one species,Oxyria digyna, demonstrated much higher microbial activity along with higher NSCs and root N, suggesting some alpine plant species may acquire nutrients through microbial interactions during snow-covered winter periods.Synthesis: This study provides the first look at the annual phenology of multiple alpine plant species and their associated rhizosphere microbiome. Our results demonstrate that seasonal microbial dynamics are highly influenced by abiotic factors (soil and microclimatic conditions), but plants are able to modulate these conditions through growth and nutrient acquisition strategies. Taken together, seasonality and independent plant species effects cannot be overlooked when assessing habitat nutrient cycling and ecosystem stability.
Two new yeast species of the genusVishniacozymaisolated from the phylloplane ofEquisetum sylvaticum
Authors: Golubev Wladyslav 
Published: February 2025

AbstractFive yeast strains belonging to the genusVishniacozymaLiu et al. were isolated from horsetail in Moscow region (Russia). By morphological and physiological properties, they are similar to the speciesV. carnescens, V. peneausandV. victoriaebut differ in mycocin-sensitivity profiles. These isolates represent two novel species, for which the namesV. equsetis(type strain VKM Y-2979) andV. paraequisetis(type strain VKM Y-2980) are proposed.
Computational modelling reveals slower safety learning and threat extinction are associated with higher anxiety severity in remote fear conditioning
Authors: Kerr Tim , Purves Kirstin , McGregor Thomas , Craske Michelle G. , Barry Tom , Lester Kathryn J. , Constantinou Elena , Sun Michael , Robinson Oliver J. , Eley Thalia C. 
Published: February 2025

AbstractAnxiety disorders are are chronic, pervasive, and debilitating; characterised by a persistent or exaggerated response to distal or abstract threats. Impaired threat discrimination (distinguishing safe from threatening stimuli) and impaired threat extinction (learning a once threatening stimulus is now safe), are known risk factors in the development and persistence of anxiety disorders. These effects can be experimentally elicited through fear conditioning. First, repeated trials of paired aversive and neutral stimuli are delivered during a fear acquisition phase, followed by repeated trials with no aversive stimuli in a fear extinction phase. The effects are typically measured through comparison of end-phase data points, or simple descriptive or statistical models. Computational modelling, by contrast, can offer a hypothesis-driven, trial-by-trial mechanistic account of fear conditioning. This unmasks within subject task variance by estimating the rate of threat learning, safety learning, and threat extinction, examining individual differences in the cognitive mechanisms behind anxiety. A normative sample (n = 145) underwent a differential fear conditioning task on a bespoke smartphone app, in addition to completing an anxiety severity measure (GAD-7). Computational models fitted to task data estimated learning rates. Whilst the threat learning rate showed no association, the threat extinction and safety learning rates showed small negative associations with anxiety severity (r = −0.218, p = 0.008 & r = −0.214, p = 0.01 respectively). These findings are in keeping with prior studies using traditional analytical approaches, and indicate that anxious individuals are not quicker to develop fear of a stimulus, but take more time than their non-anxious counterparts to learn that a stimulus is safe. This study strengthens the evidence for impairments in fear extinction in those with anxiety, and the importance of learning rates as an index of anxiety severity, a previously hidden cognitive mechanism underlying anxiety persistence.
‘Caroten-omics’ of pigments synthesised byGordonia rubropertinctathrough High Resolution Mass Spectrometry andin-silicoprogramming approach
Authors: Vemparala Gayathri , Anupoju Gangagni Rao , Kumaraguru Thenkrishnan 
Published: February 2025

ABSTRACTCarotenoids are tetraterpenoid pigments synthesised by microorganisms, plants and present in some animals. They are metabolites of importance in research and industry. The present study aimed to analyse the High Resolution Mass Spectrometry (HRMS) experimental data through R programming and identify all the carotenoids thatGordonia rubropertinctaproduces. The growth rate of the bacterium was 0.24 ± 0.132 h-1, produced about 140 ± 20 mg carotenoids/g wet cell weight (WCW) on extraction with methanol and the extract was subjected to HRMS. The number of carotenoids the bacterium synthesizes was identified to be 93 and the concentration of few carotenoids at particular time was pinpointed using R. The distinctive features of the bacterium like high number of carotenoids synthesis through various pathways, their fluctuation with respect to time, storage of carotenoids in cell cytoplasm, and its auto-fluorescent property were also discovered.
MBCO PathNet: Integration and visualization of networks connecting functionally related pathways predicted from transcriptomic and proteomic datasets
Authors: Hansen Jens , Iyengar Ravi 
Published: February 2025

SummaryOur desktop application MBCO PathNet allows for quick and easy integration and visualization of networks of functionally related pathways predicted from numerous gene and protein lists using the Molecular Biology of the Cell Ontology (MBCO) and other ontologies. Within networks of hierarchical parent-child relationships or functional relationships, pathways are visualized as pie charts where each slice represents a dataset that predicted that pathway. Sizes of pies and slices can be selected to represent statistical significance or other quantitative measures. In addition, MBCO PathNet can generate bar diagrams, heatmaps and timelines.Availability and implementationmbc-ontology.org;github.com/SBCNY/Molecular-Biology-of-the-CellContactjens.hansen@mssm.edu
CellFIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington’s Disease, Including Genetic Modifiers of Neuronal Development and Morphology
Authors: Kang Byunguk , Murphy Michael , Ng Christopher W. , Leventhal Matthew Joseph , Huynh Nhan , Im Egun , Danquah Serwah , Housman David E. , Nehme Ralda , Farhi Samouil L. , Fraenkel Ernest 
Published: February 2025

AbstractGenomic screens and GWAS are powerful tools for identifying disease-modifying genes, but it is often challenging to understand the pathways by which these genes function. Here, we take an integrated approach that combines network analysis and an imaging-based pooled genetic perturbation study to examine modifiers of Huntington’s disease (HD). The computational analysis highlighted several genes in a subnetwork enriched for modifiers of neuronal development and morphology. To test the functional roles of these genes, we developed an experimental pipeline that allows pooled CRISPRi KD of 21 genes in human iPSC-derived neurons followed by optical analysis of genotypes, neuronal arborization, multiplexed pathway activity and morphological fingerprint readout. This approach recovered known genes involved in morphology and confirmed unexpected links from the network between several genetic modifiers of HD and morphology. Our approach overcomes challenges in pooled measurement of neuronal function and health and could be adapted for other phenotypes in HD and other neurological diseases.
Impact of flushing procedures on drinking water biostability and invasion susceptibility in distribution systems
Authors: Waegenaar Fien , Pluym Thomas , Vermeulen Elise , Gusseme Bart De , Boon Nico 
Published: February 2025

AbstractMaintaining microbial stability in drinking water distribution systems (DWDS) is a priority for water providers, yet operational events like flushing and the potential invasion of unwanted microorganisms pose significant challenges. This study utilized a pilot-scale DWDS to evaluate the susceptibility of drinking water networks after standard operational flushing procedures (with and without chlorination) as these procedures can alter biostability. Results showed that flushing with chlorination reduced bulk cell counts initially but led to subsequent microbial regrowth, highlighting the limitations of chlorination in long-term biostability. Biofilm cell densities and community composition were similar before and after flushing with and without chlorination. Additionally, the susceptibility of a flushed network against introduced bacterial indicators (Aeromonas media,Pseudomonas putida, andSerratia fonticola) was investigated. The invasion experiments revealed that the species decayed more rapidly in loops flushed with chlorination. This study emphasizes the trade-off between potential regrowth and microbial control, underscoring the need for strategies that enhance microbial resilience without fostering regrowth. These findings are critical for optimizing DWDS management practices to ensure drinking water safety and quality.ImportanceFlushing, with or without chlorination, is a standard procedure used by drinking water providers to address water quality issues such as brown water, as well as following waterworks, or contaminant detection. This process involves discharging large volumes of drinking water, often through fire hydrants. Depending on the contamination, additional disinfectants, such as free chlorine, are dosed during flushing. However, the longer-term effects of these processes on microbial dynamics are unknown. For example, while brown water issues can be solved, the overall biostability of drinking water may be compromised, potentially making the drinking water distribution systems more susceptible to the invasion of unwanted microorganisms. Studying these practices in full-scale distribution networks is challenging. Therefore, in this study, a unique drinking water distribution pilot system that mimics a real network with mature biofilm was used to investigate the changes in both bulk water and biofilm microbiomes following flushing procedures.
Prevalence and mechanisms of high-level carbapenem antibiotic tolerance in clinical isolates ofKlebsiella pneumoniae
Authors: Cross Trevor , Torres Facundo , McGee Abigail P. , Aliyu Tolani , Westblade Lars F. , Singh Abhyudai , Dörr Tobias 
Published: February 2025

AbstractAntibiotic tolerance is the ability of bacteria to survive normally lethal doses of antibiotics for extended time periods. Clinically significant Enterobacterales, for example, often exhibit high tolerance to the last-resort antibiotic meropenem. Meropenem tolerance is associated with formation of cell wall-deficient spheroplasts that readily recover to rod shape and normal growth upon removal of the antibiotic. Both the true prevalence of tolerance, and genetic mechanisms underlying it, remain poorly understood. Here, we find that meropenem tolerance is widespread among clinical Enterobacterales. Using forward genetics, we uncover novel tolerance factors in a hypertolerant isolate of the ESKAPE pathogenKlebsiella pneumoniae. We find that multiple mechanisms contribute to tolerance, and that cell envelope stress responses (PhoPQ, Cpx, Rcs and OmpR/EnvZ) collectively promote spheroplast stability and recovery, while the lytic transglycosylase MltB counteracts it. Our data indicate that tolerance is widespread among clinical isolates, and that outer membrane maintenance is a key factor promoting survival of tolerantK. pneumoniae.