bluuebunny/crossref_metadata_2025 huggingface dataset:
The strength of the fecundity-immunity trade-off modulates host evolutionary dynamics, pathogen propagation, and host abundance
Authors: Djahoui Edgard , Loeuille Nicolas , Rohr Rudolf P.
Published: February 2025

In most species, life history trade-offs generate conflicts between several biological functions because of resource allocation constraints. If under a pathogenic infection, the host can trigger some defense mechanisms against the pathogen, there is usually a fitness cost associated in terms of fecundity reduction. This pattern, known as the fecundity-immunity trade-off, has received much attention, but its implications on host eco-evolutionary dynamics, and particularly on emergent properties such as host abundance and pathogen propagation remain poorly understood. Here, we use an SIR model that incorporates three distinct host immune mechanisms, which are a reduction in pathogen transmission, an increase in host recovery, and a reduction in pathogen-associated host death. Our results indicate that the effect of a fecundity-immunity trade-off depends not only on its strength, but also on the particular immune mechanism considered. We found that, in all three immune mechanisms, for a weak trade-off, the host evolves simultaneously toward high fecundity and high immunity, while for a strong trade-off, high fecundity is selected at the expense of immunity. Intermediate trade-off results in two distinct alternative evolutionary strategies; high fecundity and low immunity, and low fecundity and high immunity. Moreover, we show that disease propagation and host abundance usually show opposite dynamics along the evolutionary trajectories. We here believe that the incorporation of this trade-off in further analysis of host-pathogen interactions may help to better understand the complexity of the ecological and evolutionary dynamics in such systems.
N-Power AI: A Specialized Agent Framework for Automated Sample Size and Power Analysis in Clinical Trial Design
Authors: Ruan Peifeng , Villanueva-Miranda Ismael , Liu Jialiang , Yang Donghan M. , Zhou Qinbo , Xiao Guanghua , Xie Yang
Published: February 2025

Background

Sample size and power analysis are essential in biomedical research and investigations, particularly in clinical trial design, as they ensure sufficient statistical power to detect meaningful effects. However, the complexity of these calculations often requires specialized statistical expertise, making the process inconvenient and limiting accessibility for researchers during early-stage study planning.

Methods

We developed N-Power AI, an agentic framework leveraging large language models (LLMs) to perform sample size and power calculations across diverse study designs. The framework consists of three specialized agents: the Function Agent, a perception and reasoning module that identifies appropriate statistical tests and corresponding R functions; the Calculation Agent, an action module that extracts parameters and executes precise computations; and the Reporting Agent, a presentation module that generates comprehensive, downloadable reports. N-Power AI and advanced LLMs (e.g., GPT-o1, Claude 3.5, Gemini 1.5 Pro) were evaluated against ground truths from statistical software (R) across six common clinical trial scenarios.

Results

Direct LLM outputs showed significant deviations from ground-truth values, particularly in complex scenarios like the Chi-Square Test and Cox Proportional Hazards Model. In contrast, N-Power AI achieved 100% agreement with ground truths across all scenarios. This accuracy is attributed to the Function Agent’s correct selection of statistical methods, the Calculation Agent’s accurate computations, and the Reporting Agent’s ability to produce clear and comprehensive summaries.

Conclusion

N-Power AI automates sample size and power analysis, offering an effective, efficient, and accessible solution for early-stage study planning. While human expertise remains crucial for high-level statistical planning, N-Power AI enhances accessibility and efficiency, streamlining the analysis process to generate reliable and reproducible results for a wide range of research scenarios.
Microtubule remodeling by the innate immune factor Trim69 compromises dynein-dependent migration of HIV virion cores towards the nucleus
Authors: Vadon Charlotte , Nguyen Xuan-Nhi , Siahaan Valerie , Krishnan Arya , Henriot Veronique , Chantharath Amandine , Burlaud-Gaillard Julien , Roingeard Philippe , Janke Carsten , Etienne Lucie , Fiorini Francesca , Magiera Maria M. , Cimarelli Andrea
Published: February 2025

Like many viruses, HIV relies on the microtubule (MT) cytoskeleton for successful infection. MT-associated proteins (MAPs) regulate MT functions and thus bear the potential to modulate viral infection. However, while several MAPs are known to exert pro-viral effects on HIV, little is known about antiviral ones. We previously described the Tripartite motif protein 69 (Trim69) as an innate immune factor that remodels MTs, leading to inhibition of a broad spectrum of viruses, including HIV. Through in silico modeling, TIRF microscopy and cell-based assays, we determine that Trim69 binding to MTs is determined by a basic surface in its SPRY domain that interacts with the C-terminal tails of tubulins. This surface is conserved among mammalian Trim69s and is critical for its functions. We demonstrate that by binding and remodeling MTs, Trim69 inhibits the docking and the migration of virion cores on MTs by promoting the stalling of the dynein/dynactin motor complexes. Altogether, these findings shed light on a novel mechanism of viral defense that involves an innate immune regulation of the MT cytoskeleton.
LimROTS: A Hybrid Method Integrating Empirical Bayes and Reproducibility-Optimized Statistics for Robust Differential Expression Analysis
Authors: Anwar Ali Mostafa , Jeba Akewak , Lahti Leo , Coffey Eleanor
Published: February 2025

Motivation

Differential expression analysis plays a vital role in omics research enabling precise identification of features that associate with different phenotypes. This process is critical for uncovering biological differences between conditions, such as disease versus healthy states. In proteomics, several statistical methods have been used, ranging from simple t-tests to more advanced methods like limma and ROTS. However, a flexible method for reproducibility-optimized statistics tailored for clinical omics data has been lacking.

Results

In this study, we developed LimROTS, a hybrid method integrating the linear model and empirical Bayes method from the limma framework with the Reproducibility-Optimized Statistics from ROTS, to create a novel moderated ranking statistic, for robust and flexible analysis of proteomics data. We validated its performance using twenty-one proteomics gold standard spike-in datasets with different protein mixtures, MS instruments, and techniques for benchmarking. This hybrid approach improves accuracy and reproducibility of complex proteomics data, making LimROTS a powerful tool for high-dimensional omics data analysis.

Availability and Implementation

LimROTS has been implemented as an R/Bioconductor package, available athttps://bioconductor.org/packages/LimROTS/. Additionally, the code used in this study is available in GitHub repositoryhttps://github.com/AliYoussef96/LimROTSmanuscript

Graphical abstract
Convergent evolution of distinct D-ribulose utilisation pathways in attaching and effacing pathogens
Authors: Cottam Curtis , Bowran Kieran , White Rhys T. , Baslé Arnaud , Josts Inokentijs , Connolly James PR
Published: February 2025

Attaching and effacing pathogens overcome colonisation resistance by competing with metabolically similar organisms for limited resources. EnterohaemorrhagicE. coli(EHEC) utilises the pathogenicity island-encoded Accessory ʟ-arabinose Uptake (Aau) transporter to effectively colonise the mouse gut, hypothesised to be achieved via an enhanced capacity to scavenge ʟ-arabinose. Aau is regulated exclusively in response to ʟ-arabinose, but it is unclear how this system specifically benefits EHECin vivo. Here, we show that Aau displays a >200-fold higher affinity for the monosaccharide D-ribulose, over ʟ-arabinose. EHEC cannot grow on D-ribulose as a sole carbon source and this sugar does not triggeraautranscription. However, Aau effectively transports D-ribulose into the cell only in the presence of ʟ-arabinose, where it feeds into the pentose phosphate pathway, after phosphorylation by the ʟ-ribulokinase AraB, thus providing EHEC a significant fitness advantage. EHEC has therefore evolved a mechanism of hijacking the canonical ʟ-arabinose utilisation machinery to promote D-ribulose utilisationin vivo. Furthermore,Citrobacter rodentiumencodes an analogous system that exclusively transports D-ribulose and metabolises it via a dedicated D-ribulokinase. These unique mechanisms of D-ribulose utilisation suggest that convergent evolution has driven the ability of distinct pathogenic species to exploit this nutrient during invasion of the gut niche.
RNAprecis: Prediction of full-detail RNA conformation from the experimentally best-observed sparse parameters
Authors: Wiechers Henrik , Williams Christopher J. , Eltzner Benjamin , Hoppe Franziska , Prisant Michael G. , Chen Vincent B. , Miller Ezra , Mardia Kanti V. , Richardson Jane S. , Huckemann Stephan F.
Published: February 2025

We address the problem of predicting high detail RNA structure geometry from the information available in low resolution experimental maps of electron density. Here low resolution refers to ⪆ 2.5Åwhere the location of the phosphate groups and the glyocosidic bonds can be determined from electron density but all other backbone atom positions cannot. In contrast, high resolution determines all backbone atomic positions. To this end, we firstly create a gold standard data base for four groups of manually corrected suites, each reflecting one out of four sugar pucker-pair configurations. Secondly we develop and employ a modified version of the previously devised algorithm MINT-AGE to learn clusters that are in high correspondence with gold standard’s conformational classes based on 3D RNA structure. Since some of the manually corrected classes are of very small size, the modified version of MINT-AGE is able to also identify very small clusters. Thirdly, the new algorithm RNAprecis assigns low resolution structures to newly designed 3D shape coordinates. Our improvements include: (i) learned classes augmented to cover also very low sample sizes and (ii) regularizing a key distance by introducing an adaptive Mahalanobis distance. On a test data containing many clashing and suites modeled as conformational outliers, RNA precis shows good results suggesting that our learning method generalizes well. In particular, our modified MINT-AGE clustering can be finer than the existing curated gold standard suite conformers. For example, the0aconformer has been separated into two clusters seen in different structural contexts. Such new distinctions can have implications for biochemical interpretation of RNA structure.

Code availabilit

The code used to generate the analyses and plots presented in this paper can be foundhttps://gitlab.gwdg.de/henrik.wiechers1/rnaprecis
Diversity, structure-function relationships and evolution of cell wall-binding domains of staphylococcal phage endolysins
Authors: Vázquez Roberto , Gutiérrez Diana , Criel Bjorn , Dezutter Zoë , Briers Yves
Published: February 2025

Endolysins, encoded by phages, lyse bacterial hosts at the end of the replication cycle by degrading peptidoglycan. Consequently, they have evolved in response to host cell wall structures, leading to complex modular architectures, particularly in Gram-positive bacteria. These architectures feature diverse enzymatically active domains (EADs) and cell wall-binding domains (CBDs).

This study investigates the structure-function relationships of CBDs in staphylococcal phage endolysins, exploring their evolutionary origins and the extent to which binding specificity can be predicted from sequence data. A set of 182 staphylococcal endolysin sequences was analyzed, revealing predominantly three-domain architectures, occasionally disrupted by species-specific mobile genetic elements. Most CBDs exhibited an SH3-like fold, classified into two major subfamilies: SH3b_P (including the well-characterized SH3_5 family) and SH3b_T. The composition of endolysin domains correlated with specific CBD families, suggesting co-evolution of CBDs and compatible EADs to ensure functional synergy.

To assess binding properties, 24 CBDs were fused to eGFP and tested against a panel of staphylococci, revealing diverse specificity profiles. However, no clear correlation emerged between binding specificity, phylogenetic subgroups, or bacterial hosts. This suggests that minor structural modifications significantly impact function and that CBD specificity is not a major selective pressure in the staphylococcal bacteria-phage interface.
The offensive role of theBacillusextracellular matrix in driving metabolite-mediated dialogue and adaptive strategies with pathogenic fungi
Authors: Pérez-Lorente Alicia I. , Molina-Santiago Carlos , Vela-Corcía David , Stincone Paolo , Hierrezuelo Jesús , Grifé Montserrat , Pakkir Shah Abzer K. , de Vicente Antonio , Petras Daniel , Romero Diego
Published: February 2025

Bacterial□fungal interactions have traditionally been attributed to secondary metabolites, but the role of the bacterial extracellular matrix (ECM) in shaping these relationships has remained unclear. Here, we demonstrate that the ECM protein TasA is a key mediator in the antagonistic interaction betweenBacillus subtilisandBotrytis cinerea. TasA enablesBacillusto tightly adhere to fungal hyphae, disrupts the β-glucan layer, and compromises fungal cytoskeletal integrity synergistically with fengycin, which causes cytological damage. Additionally, TasA acts as a carrier for bacillaene, amplifying its fungistatic activity. In response,B. cinereamounts a multifaceted defense, enzymatically degrading fengycin, producing antibacterial oxylipins, and activating adaptive programs such as hyphal branching and chlamydospore formation. Our findings reveal the previously unrecognized role of ECM components in fungal suppression and the modulation of fungal adaptive responses. This study reveals the complex interplay between microbial aggression and defense, providing new insights into the ecological dynamics of microbial competition and coexistence.
ggalign: Bridging the Grammar of Graphics and Biological Multilayered Complexity
Authors: Peng Yun , Song Yuxuan , Luo Peng , Li Jianfeng , Zhou Jian-Guo , Yu Guangchuang , Xu Tao , Wang Shixiang
Published: February 2025

Composable visualization is essential in biomedical research, particularly when working with complex, multi-dimensional biological data. However, many existing tools focus on specific fields and lack the comprehensive features needed to capture the intricacies and interrelations of datasets. To address this, we introduce ggalign, an R package built on the grammar of graphics framework, providing an easy-to-use platform for creating composable visualizations of interconnected data. It offers a variety of layout options, includingStackLayout, QuadLayout, andCircleLayout, tailored to different data types, and supports flexible multi-dimensional relationships, such as one-to-many, many-to-one, many-to-many, and crosswise connections. Additionally, ggalign enhances the clarity of visualizations through its annotation features. Overall, ggalign offers a powerful and flexible solution for visualizing complex data in biomedical research.

Abstract Figure
Ecology and pathogenicity for honey bee brood of recently described Paenibacillus melissococcoides and comparison with Paenibacillus dendritiformis, Paenibacillus thiaminolyticus
Authors: Ory Florine , Dainat Benjamin , Wuergler Oliver , Wenger Fabian , Roetschi Alexandra , Braillard Laurianne , Charriere Jean-Daniel , Dietemann Vincent
Published: February 2025

Honey bee colonies contain thousands of individuals living in close proximity in a thermally homeostatic nest, creating ideal conditions for the thriving of numerous pathogens. Among the bacterial pathogens, Paenibacillus larvae infects larvae via the nutritive jelly that adult workers feed them, causing the highly contagious American foulbrood disease. Further Paenibacillus species were anecdotally found in association with honey bees, including when affected by another disease, European foulbrood (EFB). However, their pathogenicity remains largely unknown. Our results indicate that Paenibacillus dendritiformis, Paenibacillus thiaminolyticus and newly described Paenibacillus melissococcoides are pathogenic towards honey bee brood and that their virulence correlates with their sporulation ability, which confers them resistance to the bactericidal properties of the nutritive jelly. Our survey occasionally but increasingly detected P. melissococcoides in confirmed and idiopathic cases of EFB but never in healthy colonies, suggesting that this bacterium is an emerging pathogen of honey bee brood. Overall, our results suggest that virulence traits allowing a pathogenic or opportunistically pathogenic habit towards honey bee brood are frequent in Paenibacillus spp., but that their degree of adaptation to this host varies. Our study clarifies the ecology of this ubiquitous genus, especially when infecting honey bees.
A dWDR45 knock-outDrosophilamodel to decipher the role of autophagy in BPAN
Authors: Celle Marion , Aniorte Sahra , Issa Abdoul Raouf , Jollivet Florence , Falabregue Marion , Jin Haixiu , Ding Shuze , Seugnet Laurent , Liao Lujian , Lesca Gaetan , Walter Ludivine , Mollereau Bertrand
Published: February 2025

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurological disease characterized by severe cognitive and motor impairments. BPAN is caused byde novopathogenic variants in theWDR45gene on the X chromosome.WDR45gene encodes the protein WDR45/WIPI4, a known regulator of autophagy. A defective autophagy has been observed in cellular models of BPAN disease and is associated with neurological dysfunctions inWDR45knockout (KO) mice. However, it remains unclear whether the autophagic defect directly contributes to all WDR45 loss-induced phenotypes or whether other WDR45-dependent cellular functions are involved. To investigate this, we generated a CRISPR/Cas9-mediated KO ofCG11975(dwdr45KO), theDrosophilahomolog ofWDR45. Our analysis revealed thatdwdr45KO flies display BPAN-like phenotypes, including impaired locomotor function, autophagy dysregulation and iron dyshomeostasis. Additionally,dwdr45KO flies exhibit shorten lifespan compared to control flies. These findings demonstrate thatdwdr45KO fly is a relevant model for investigating the key cellular and molecular mechanisms underlying BPAN-associated phenotypes. Notably, induction of autophagy indwdr45KO flies partially rescued the shortened lifespan, but did not restore locomotor function. This suggests that defective autophagy contributes to some, but not all, aspects of the phenotypes resulting from loss ofdwdr45function.
A truncation library for the soluble production of squalene synthase fromCandida albicansinEscherichia coli
Authors: Tolmie Carmien , Opperman Diederik J.
Published: February 2025

The rising global burden of infectious fungal disease and the steady increase of resistance by fungal pathogens to available treatments necessitate a concerted effort to develop new antifungal medicines. Squalene synthase is a critical enzyme in the synthesis of ergosterol, a fungal-specific sterol, and has not yet been exploited as an antifungal drug target for pathogenic yeast. In this study, we heterologously produce squalene synthase (SQS) from the opportunistic pathogenCandida albicansinEscherichia colito obtain high-quality pure protein for structural studies. A library of nine C- or N&C-terminally truncated SQS variants was successfully produced and purified with immobilised metal-affinity chromatography (IMAC). Two variants were upscaled and purified to near-homogeneity, but size-exclusion chromatography showed possible aggregation. Nevertheless, this study provides a starting point to further optimise buffer conditions to produce high-quality heterologous SQS fromC. albicansfor downstream crystallography experiments.
Cerebellar climbing fibers convey perceptual choice during decision-making
Authors: Yiu Tin Long , Wilson Evan A. , Yahiro Takaki , Ma Lei , Qin Maozhen , Zhong Haining
Published: February 2025

Cerebellar climbing fibers are thought to signal reward prediction errors in non-motor functions. By imaging postsynaptic responses of climbing fibers onto mouse Purkinje cell dendrites during auditory discrimination, we found that climbing fibers in crus I can encode cue identities or perceptual choices. These responses were reshaped by reversal learning. Optogenetic perturbation of climbing fiber activity impaired discrimination. These results suggest a feedforward role of climbing fibers in perceptual decision-making.
I helix Mediates the Allosteric Regulation in Cytochrome P450cam
Authors: Sahil Mohammad , Mondal Jagannath
Published: February 2025

Cytochrome P450cam, a key monooxygenase in the P450 superfamily, is pivotal in metabolic and industrial processes. Despite extensive studies, a unified mechanism governing its conformational heterogeneity, substrate-dependent allostery, and multi-substrate binding remains elusive. Here, integrating molecular dynamics simulations, NMR pseudocontact shift (PCS) analysis, and crystallographic data, we identify the I-helix (αI) as the central regulator of P450cam’s allostery. Its intrinsic flexibility, dictated by glycine residues (G248 and G249), orchestrates enzyme conformational dynamics. Specifically,αI transitions betweenstraightandkinkedconformations, modulating the opening and closing of substrate access channels (channel-1 and channel-2) and mediating allosteric communication between active and allosteric sites. Substrate binding stabilizes thestraightconformation, promoting channel closure and enhancing allosteric regulation. This I-helix-based mechanism reconciles 125 crystallographic poses, spanning straight-to-kinkedαI conformations. Notably, the kink-inducing glycine G249 is evolutionarily conserved across species, including humans, underscoringαI’s fundamental role in enzyme function and broader significance within the P450 superfamily. NMR PCS measurements align with the kinked and straight conformations in the substrate-free and substrate-bound states, with Q-scores of 0.108 and 0.061, respectively. Leveraging this mechanistic insight, we designed proof-of-concept P450cam mutants locked in either constitutively open or closed conformations for the first time. By shifting the focus from the traditional FG-helix-centric view to an I-helix-centric framework, this study provides a comprehensive blueprint for conformational and allosteric regulation, paving the way for engineering tailored P450 variants.
Applications of Artificial Intelligence in Neurosurgical Education: A Scoping Review
Authors: Piñera-Castro Hector Julio , Borges-García Christian
Published: February 2025

Background

Artificial intelligence (AI) has revolutionized medical education due to its capacity to optimize instruction, assess competencies, and tailor learning. Given the interdisciplinary nature and transformative potential of AI, its integration into neurosurgical education merits thorough examination.

Objective

To evaluate systematically the applications of AI in neurosurgical education.

Methods

A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Original observational and experimental studies published in peer-reviewed journals that investigated the use of AI in neurosurgical education were included. The search was carried out in Scopus up to May 2024, and studies not written in English or Spanish were excluded. The selection process and data extraction were performed independently by two reviewers. A narrative synthesis approach was employed.

Results

Twenty-three studies were selected, identifying four main areas. In board examination performance, advanced models like ChatGPT-4 outperformed previous versions and residents in answering neurosurgical exam questions, achieving higher accuracy in complex theoretical and image-based inquiries. In simulation training and tutoring, neural networks analyzed surgical simulation data, classifying participants by expertise levels and providing individualized, metric-based feedback that improved technical skills and identified distinct learning patterns among trainees. In performance evaluation, machine learning techniques assessed surgical skills during simulations with high accuracy, identifying key behavioral metrics associated with expertise. Other innovative applications included AI for neuroanatomical segmentation in imaging studies, analysis of surgical instrument utilization patterns through computer vision, and generation of academic content. These studies highlighted AI’s multifaceted roles and ethical considerations, such as overreliance risks and the need for robust databases and realistic simulations.

Conclusions

AI has enhanced neurosurgical education by improving knowledge assessment, simulation training, and performance evaluation. Despite its transformative potential, ethical and technical challenges persist. The continuous development of AI models and their responsible implementation are recommended to further optimize neurosurgical training and ensure safe integration into educational curricula.
Circulating causal protein networks linked to future risk of myocardial infarction
Authors: Bankier Sean , Gudmundsdottir Valborg , Jonmundsson Thorarinn , Bjarnadottir Heida , Loureiro Joseph , Wang Lingfei , Finkel Nancy , Orth Anthony P , Aspelund Thor , Launer Lenore J , Björkegren Johan LM , Jennings Lori L , Lamb John R , Gudnason Vilmundur , Michoel Tom , Emilsson Valur
Published: February 2025

Variations in blood protein levels have been associated with a broad spectrum of complex diseases, including atherosclerotic cardiovascular disease (ACVD). These associations highlight the intricate interplay between local (e.g., cardiovascular) and systemic (non-cardiovascular) factors for the development of ACVD, emphasizing the need for a comprehensive, systems-level understanding of its etiology. To accomplish this, we developed a causal network inference framework by analyzing one of the largest serum proteomics studies to date, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES), a prospective population-based study of 7,523 serum proteins measured in 5,376 older adults. To reconstruct a causal network of serum proteins, we usedcis-acting protein quantitative trait loci (pQTLs) as instrumental variables to infer causal relationships between protein pairs, while accounting for potential unobserved confounding factors. We identified 185 causal protein subnetworks (FDR = 1%, n ≥ 10 members), which collectively interacted with 5,611 target proteins, offering valuable biological insights and an overview of systemic homeostasis. Several subnetworks, many of which interact to establish a hierarchy of directional relationships, were significantly associated with future myocardial infarction and/or its long-term complications like heart failure, as well as with key cardiometabolic traits that contribute to the onset of ACVD.
The impact of deprivation and neighbourhood food environments on home food environments, parental feeding practices, and child eating behaviours, food preferences and BMI: The Family Food Experience Study-London
Authors: Smith Andrea , Kininmonth Alice , Tommerup Kristiane , Boniface David , Gericke Chiara , Denning Tiffany , Summerbell Carolyn , Vogel Christina , Llewellyn Clare
Published: February 2025

Purpose

Childhood obesity inequalities in England persist despite targeted interventions focused on promoting healthy diets and food environments. This study, part of the Family Food Experience Study-London, aimed to investigate the impact of deprivation and neighbourhood food environments on home food environments, parental feeding practices, child eating behaviours, food preferences, and child BMI.

Methods

Families (n=728) with primary school-aged children were recruited from four socioeconomically diverse London boroughs in 2022. Data were collected through computer-assisted interviews (30.8% in-person, 69.2% telephone) on home food environment, parental feeding practices, and children’s eating behaviours and food preferences. Deprivation was characterised using a composite measure of family and neighbourhood indicators of socioeconomic position. Neighbourhood food environment exposures were derived from individualised activity spaces. Child BMI was measured objectively. Generalised linear models examined associations between deprivation and neighbourhood food environment with family food-related outcomes, adjusting for school-level clustering, child sex, age and ethnicity.

Results

Greater neighbourhood deprivation was significantly associated with more ‘obesogenic’ family food practices, child eating behaviours and child BMI. Deprivation was linked to higher food responsiveness (β=-0.12, p=0.002), emotional overeating (β=-0.11, p <0.001), and increased desire to drink (β=-0.26, p <0.001). Parents in deprived households used more emotional (β=-0.10, p<0.05), instrumental (β=-0.11, p=0.003) and pressuring feeding practices (β=-0.14, p<0.001). Greater deprivation was also associated with a more obesogenic home food environment (β=-0.19, p<0.001) and lower meal structure (β= 0.17, p<0.001). Exposure to less healthy neighbourhood food environments around and between home and school were associated with a more obesogenic home food environment (β=-0.07, p<0.01), but no significant associations were found with feeding practices or child eating behaviours or child BMI.

Conclusions

Family deprivation, rather than neighbourhood food environments, is more strongly linked to obesogenic feeding practices, child eating behaviours and child BMI. Policies focusing on improving neighbourhood food environments will likely be most effective if combined with those addressing systemic issues related to deprivation such as welfare policies (e.g. reforms to benefit caps) or targeted subsidies for healthy food. Future research should examine the independent and accumulative impact that environment and household interventions have on childhood obesity inequalities.
Exercise Crystal: simulations that drive National IHR Focal Point capacity strengthening
Authors: Goddard Laura , Khut Qiu Yi , Samaan Gina
Published: February 2025

The International Health Regulations (IHR 2005) require States Parties to designate a National IHR Focal Point (NFP) for timely IHR communications with the World Health Organization (WHO) and, following recent amendments, to designate a National IHR Authority to coordinate IHR implementation within States Parties. Since 2008, the WHO Regional Office for the Western Pacific has been supporting the strengthening and testing of NFP functionality through an annual simulation exercise known as IHR Exercise Crystal. This study analyses NFP performance during IHR Exercise Crystal over a 16-year period to inform Member States’ planning for NFP capacity strengthening, in the context of the recent IHR amendments. Exercise monitoring data were analysed using descriptive statistics across six key NFP performance indicators. Findings show consistently high NFP accessibility via email (mean: 99%) but suboptimal NFP accessibility via telephone (mean: 64%). NFP participation in tele- and videoconferences improved over time (mean: 73%), as did the proportion of NFPs notifying WHO of simulated events (mean: 80%) and contributing information to Event Information Site postings (mean: 77%). Multisectoral communication remained variable with no clear trend (mean: 73%). This demonstrates that significant progress has been made and that opportunities remain to further enhance NFP functionality, particularly in the areas of NFP accessibility and multisectoral coordination. It is critical that States Parties continue strengthening and testing NFP functionality through simulation exercises and other capacity-building to ensure effective IHR implementation. Furthermore, States Parties should develop, test and maintain up-to-date SOPs to support the clear demarcation of roles and responsibilities between the NFP and the National IHR Authority.
Practice-level variation in the provision of subsidized dental services to adult Danes in 2019: A register-based study
Authors: Raittio Eero , Baelum Vibeke
Published: February 2025

Objectives

The aim was to investigate practice-level variation in common dental diagnostic, preventive, and care services provided for Danish adults who underwent a dental examination.

Methods

This was a nationwide register-based study. Subsidized dental services delivered during the 13-week-period subsequent to the provision of one of three eligible dental examinations (extended, basic, or recall examination) during the first nine months of 2019 were investigated. Bayesian multilevel regression models were used to estimate the practice-level average predicted probability of supragingival care, subgingival care, individual prevention, bitewing radiographs, and endodontic treatment, and the average predicted count of extractions and direct restorations while adjusting for individual sociodemographics and dental treatments received during the previous 10 years.

Results

The final sample included 445,516 examinations conducted in 1,593 dental practices. Supragingival care after basic or recall examinations showed the lowest practice-level variation, with around two-fold difference between top and bottom 2.5%. Individual preventive services after recall examinations showed the highest variation with over 30-fold difference between top and bottom 2.5%. All other outcomes showed around 3- to 8-fold differences between practices at top and bottom 2.5% across all examination types. The differences across practices were smaller—1.2- to 3.0-fold—when the top 25% and bottom 25% were compared instead.

Conclusions

This study found considerable variation in diagnostic, preventive, and treatment services provided for Danish adults who underwent a dental examination. The findings highlight the need for research that can inform evidence-based practice through the development of quality clinical practice guidelines, continuing education programs, and closer surveillance of care delivery.
Nim1-related kinases regulate septin organization and cytokinesis by modulating Hof1 at the cell division site
Authors: Bhojappa Bindu , Dhar Anubhav , VT Bagyashree , Kumari Jayanti , Cardozo Freya , Rizvi Vaseef , Palani Saravanan
Published: February 2025

The septin scaffold recruits and organizes the actomyosin ring (AMR) components, thus ensuring faithful cytokinesis. The septin-associated kinases - Elm1, Gin4, Hsl1, and Kcc4 are believed to stabilize the septins at the bud neck, but the underlying mechanisms are largely unknown. Here, we present a comprehensive, quantitative analysis of these four septin regulatory kinases and reveal major roles for Elm1 and Gin4 in septin stability. We find that Elm1 and Gin4 play an overlooked role in actomyosin ring organization and constriction. We report that Gin4 kinase directly interacts with F-BAR protein Hof1 via its C-terminal membrane-binding domain and may be involved in proper organization and anchoring of AMR component Hof1 at the bud neck, representing an unappreciated mode of regulation of cytokinesis by the septin kinase network. We also show that Gin4 controls septin organisation and AMR constriction in a kinase-independent manner similar to Elm1. We have also performed an extensive GFP-GBP-based tethering screen in Δelm1and Δgin4cells and found an important role for Hsl1 in maintaining septin organisation and cell shape in coordination with Elm1, Gin4, and Kcc4. Furthermore, our data indicate that Hsl1 acts downstream of Elm1, with its membrane-binding KA1 domain being critical for its function. Together, these findings reveal new insights into modes of cytokinesis regulation by kinases Gin4 and Elm1 and highlight a redundant role for Hsl1 in controlling septin organization and cytokinesis, revealing the in-built adaptability of the septin kinase network inS. cerevisiae.
stDyer-image improves clustering analysis of spatially resolved transcriptomics and proteomics with morphological images
Authors: Xu Ke , Zhou Xin Maizie , Zhang Lu
Published: February 2025

Spatially resolved transcriptomics (SRT) and spatially resolved proteomics (SRP) data enable the study of gene expression and protein abundances within their precise spatial and cellular contexts in tissues. Certain SRT and SRP tech-nologies also capture corresponding morphology images, adding another layer of valuable information. However, few existing methods developed for SRT data effectively leverage these supplementary images to enhance clustering performance. Here, we introduce stDyer-image, an end-to-end deep learning framework designed for clustering for SRT and SRP datasets with images. Unlike existing methods that utilize images to complement gene expression data, stDyer-image directly links image features to cluster labels. This approach draws inspiration from pathologists, who can visually identify specific cell types or tumor regions from morphological images without relying on gene expression or protein abundances. Benchmarks against state-of-the-art tools demonstrate that stDyer-image achieves superior performance in clustering. Moreover, it is capable of handling large-scale datasets across diverse technologies, making it a versatile and powerful tool for spatial omics analysis.
Topological conditions of gene regulatory networks enabling robust binary cell-fate decision-making
Authors: Shyam Sai , Nandan Nikhil , Jolly Mohit Kumar , Hari Kishore
Published: February 2025

Embryonic development entails multi-layer branching of cell-fate decision processes; often, each branch corresponding to a binary cell-fate decision. The two phenotypes at such branching points usually have mutually exclusive gene expression patterns, driven by two master regulators that mutually inhibit each other and can activate themselves, forming a toggle switch. The dynamics of a toggle switch have been extensively studied, however, the regulatory networks underlying cell-fate decision often involve many transcription factors. We recently showed that these networks can be organized as two mutually inhibiting “teams of nodes”, such that the nodes of the same team predominantly activate themselves, while those of the opposite teams primarily inhibit each other. While the ideal cases of fully connected and consistent networks of two “teams of nodes” have been well-understood, a detailed understanding of the effect of varying levels of connectivity and inconsistency in the edges with respect to the configuration of teams is lacking. Here, we simulate networks of two-teams (TTN) under varying degrees of edge density, edge impurity and external influence to identify the conditions under which these networks can give rise to a robust binary cell-fate decision system. We find that the emergent cell-fate decision landscape is much more sensitive to inconsistent edges than to low connectivity, and that TTN generally lead to a more robust landscape than a toggle switch in the context of buffering external perturbations. Our results offer insights into the design principles of gene regulatory networks engaged in binary cell-fate decisions and can be extended to evaluate strategies for cellular reprogramming.
Elucidation andde novoReconstitution of Glyceollin Biosynthesis
Authors: Sun Yunlong , Chen Cong , Lin Chao , Zhang Hao , Lian Jiazhang , Hong Benke
Published: February 2025

Glyceollins are phytoalexins produced by soybeans in response to stressors such as pathogen invasion, injury, and environmental challenges. In addition to their antibacterial and antifungal activities, these compounds have attracted significant attention for their potential anticancer, anti-inflammatory, and antioxidant properties. However, their limited accessibility-due to the challenges and high costs associated with organic synthesis or purification from treated soybean seedlings-has hindered further physiological and biochemical studies. Moreover, the incomplete understanding of glyceollin biosynthesis, particularly the final cyclization steps, remains a major barrier to elucidating their physiological functions and achieving sustainable production through synthetic biology. In this study, we identified previously uncharacterized genes encoding two reductases for 7,2’,4’-trihydroxy-isoflavanol (THI) synthesis and five P450 enzymes responsible for the final oxidative cyclization in glyceollins I, II, and III biosynthesis, thereby completing the entire biosynthetic pathway. By reconstructing the pathwayde novothrough synthetic biology, we achieved the successful production of glyceollins from simple carbon sources in Baker’s yeast. This work advances understanding of glyceollin biosynthesis, facilitates sustainable production in microbial hosts and offers new opportunities for their applications in agriculture and biology.
E2A SUMOylation promotes HAdV mediated inhibition of the tumor suppressor p53 during infection
Authors: Stubbe Miona , Stubbe Hans Christian , Mai Julia , Plank Verena , Hofmann Samuel , Göttig Lilian , Günther Thomas , Grundhoff Adam , Krebs Stefan , Groitl Peter , Mayerle Julia , Hay Ron T. , Dobner Thomas , Schreiner Sabrina
Published: February 2025

HAdV express early viral genes to modulate the activity of the cellular tumor suppressor p53 and ensure efficient viral replication, through various processes, whilst some of them are not completely understood. HAdV oncoprotein E1B-55K interactions with SUMO, PML-IV/V and Sp100A are tightly connected to the transforming potential of the viral factor in non-lytic infections. SUMO modified HAdV DNA binding protein (DBP) E2A interacts with PML and Sp100A acting as a molecular bridge between viral replication centers (RCs) and PML tracks. Here, we show for the first time, that HAdV E2A is involved in the inhibition of p53 activity and apoptosis and thus identified a novel route of exhibiting virus induced oncogenic potential. We revealed an E1B-55K independent localization of p53 within HAdV replication centers marked by E2A. In the absence of any functional E1B-55K protein expression, p53 interacts with E2A. E2A SUMOylation promotes HAdV-mediated inhibition of p53/DNA binding and p53-dependent transactivation by supporting p53 degradation, E1B-55K interaction and colocalization with PML-V that leads to E1B-55K induced upregulation of p53 SUMOylation. In sum, we provide evidence for a novel mechanism by which the HAdV DBP E2A protein inhibits p53-mediated transcriptional activation and apoptotic host cell response. Intriguingly, these findings change the longstanding dogma of host DNA damage response (DDR) inactivation by HAdV infection and offer crucial insights to improve future p53 selective oncolytic virus therapies and adenoviral vectors.
Intraspecies associations from strain-rich metagenome samples
Authors: Qu Evan B. , Baker Jacob S. , Markey Laura , Khadka Veda , Mancuso Chris , Tripp Delphine , Lieberman Tami D.
Published: February 2025

Genetically distinct strains of a species can vary widely in phenotype, reducing the utility of species-resolved microbiome measurements for detecting associations with health or disease. While metagenomics theoretically provides information on all strains in a sample, current strain-resolved analysis methods face a tradeoff:de novogenotyping approaches can detect novel strains but struggle when applied to strain-rich or low-coverage samples, while reference database methods work robustly across sample types but are insensitive to novel diversity. We present PHLAME, a method that bridges this divide by combining the advantages of reference-based approaches with novelty awareness. PHLAME explicitly defines clades at multiple phylogenetic levels and introduces a probabilistic, mutation-based, framework to accurately quantify novelty from the nearest reference. By applying PHLAME to publicly available human skin and vaginal metagenomes, we uncover previously undetected clade associations with coexisting species, geography, and host age. The ability to characterize intraspecies associations and dynamics in previously inaccessible environments will propel new mechanistic insights from accumulating metagenomic data.
‘Trans-differentiation of neutrophils from plasmablast’ is an artefact caused by over-reliance on machine algorithms in single cell RNA sequencing analysis: Lesson learnt and steps ahead
Authors: Huang Jinghan , Yam Phillip S.C. , Tang Nelson L.S.
Published: February 2025

Single cell RNA sequencing (scRNA-seq) provides new opportunities to characterize gene expression for individual cells. However, the sparse nature of the scRNA-seq data with many zero counts or missing values presents a major challenge to its analysis. The presence of low-quality cells further complicates the analysis. Here, we showed that the trans-differentiation of plasmablasts (activated plasma cells) into neutrophils reported in COVID patients (Wilk et al., 2020 in Nature Medicine) was an artefact of trajectory analysis. It was caused by ∽30 low-quality cells linking the 2 cell populations that are of unrelated lineages in hematopoietic differentiation.

Such artefacts are not readily spotted during the current practice of peer reviews as the current statistical guidelines of most journals are not catered for big data such as that of scRNA-seq. New standards of statistics and quality control measures for machine algorithms are not in place and they are urgently needed to safeguard against over-interpretation of high dimensional data. We propose a comprehensive framework to ensure reproducibility in high-dimensional data analysis, emphasizing quality checks, sensitivity analyses, alternative and multiple algorithms validation. Finally, and most importantly, a hypothesis-driven research approach should be upheld.
Niche-driven phenotypic plasticity and cis-regulatory dynamics of a revised model for intestinal secretory differentiation
Authors: Bhattacharya Swarnabh , Tei Guodong , Singh Pratik Narendra Pratap , Malagola Ermanno , Eskiocak Onur , He Ruiyang , Kraiczy Judith , Gu Wei , Perlov Yakov , Beyaz Semir , WANG TIMOTHY Cragin , Zhou Qiao , Shivdasani Ramesh Arjun
Published: February 2025

Enterocytes and four secretory cell types derive from stem cells located in intestinal crypts. Whereas secretory goblet and Paneth cells have long been considered distinct, we find high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of sibling enteroendocrine or tuft cells. Mouse and human goblet and Paneth cells express extraordinary fractions of selective antimicrobial genes, reflecting specific and variable gene responses to local niche signals. Wnt signaling retains few ATOH1+ secretory daughters in crypt bottoms, where an absence of BMP signaling potently induces Paneth features; those that move away from crypt bottoms acquire classic goblet properties. These post-mitotic cellular phenotypes and their underlying accessible cis-elements interconvert readily. Thus, goblet and Paneth properties represent alternative manifestations of a single versatile signal-responsive secretory cell. These findings reveal exquisite niche-dependent cell plasticity and the cis-regulatory dynamics of an updated unitarian model of the intestinal epithelial lineage.