bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia-induced histone methylation and NF-κB activation in pancreas cancer fibroblasts promote EMT-supportive growth factor secretion
Authors: Kowalewski Karl M. , Adair Sara J. , Talkington Anne , Wieder Jason J. , Pitarresi Jason R. , Perez-Vale Kia , Chu Britney , Dolatshahi Sepideh , Sears Rosalie , Stanger Ben Z. , Bauer Todd W. , Lazzara Matthew J.
Published: February 2025

The pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment contains hypoxic tissue subdomains and cancer-associated fibroblasts (CAFs) of multiple subtypes that play tumor-promoting and -restraining roles. Here, we demonstrate that hypoxia promotes an inflammatory-like CAF phenotype and that hypoxic CAFs selectively promote epithelial-mesenchymal transition (EMT) in PDAC cancer cells through growth factor-mediated cell crosstalk. By analyzing patient tumor single-cell transcriptomics and conducting an inhibitor screen, we identified IGF-2 and HGF as specific EMT-inducing growth factors produced by hypoxic CAFs. We further found that reactive oxygen species-activated NF-κB cooperates with hypoxia-dependent histone methylation to promote IGF-2 and HGF expression in hypoxic CAFs. In lineage-traced autochthonous PDAC mouse tumors, hypoxic CAFs resided preferentially near hypoxic, mesenchymal cancer cells. However, in subcutaneous tumors engineered with hypoxia fate-mapped CAFs, once-hypoxic re-oxygenated CAFs lacked a spatial correlation with mesenchymal cancer cells. Thus, hypoxia promotes reversible CAF-malignant cell interactions that drive EMT through druggable signaling pathways.

One-sentence summary

We show that hypoxic fibroblasts in pancreas cancer leverage histone methylation and ROS-mediated NF-κB activation to produce growth factors that drive epithelial-mesenchymal transition in malignant cells, demonstrating how tumor stromal features cooperate to initiate a signaling process for disease progression.
Impaired Macrophage DNase Secretion Promotes Neutrophil Extracellular Trap Mediated Defective Efferocytosis in Atherosclerosis
Authors: Dhawan Umesh Kumar , Vartak Tanwi , Englert Hanna , Singhal Aarushi , Chakraborty Rahul , Bhagat Karran Kiran , Vasconcellos Luiz Ricardo C. , McDonnell Ciaran , Connolly Mary , Mulkern Edward , O’Donohoe Martin , Gelderblom Mathias , Renne Thomas , Godson Catherine , Brennan Eoin , Subramanian Manikandan
Published: February 2025

Neutrophil extracellular traps (NETs) drive atherosclerosis progression and are associated with adverse clinical outcomes like myocardial infarction and stroke. While the triggers of NETosis in atherosclerotic plaque are well-characterized, the mechanisms underlying NET degradation and clearance remain unclear. Moreover, the impact of impaired NET clearance on atherosclerosis progression have not been elucidated. Here we show that macrophages are critical for the release of DNases, which degrade NETs. We identified endoplasmic reticulum (ER) stress mediated activation of PERK-ATF4 pathway as a key driver of impaired macrophage DNase secretion, leading to delayed NET clearance and their persistence. Elevated NET levels trigger cleavage of the efferocytosis receptor Mertk leading to defective macrophage efferocytosis and exacerbation of plaque necrosis. Human atherosclerotic plaques andLdlr-/-mice treated with ISRIB, a PERK inhibitor, show enhanced DNase secretion and clearance of NETs. Together, the identification of key mechanisms of NET clearance in atherosclerosis offers new therapeutic strategies to stabilize plaques.
GenomeOcean: An Efficient Genome Foundation Model Trained on Large-Scale Metagenomic Assemblies
Authors: Zhou Zhihan , Riley Robert , Kautsar Satria , Wu Weimin , Egan Rob , Hofmeyr Steven , Goldhaber-Gordon Shira , Yu Mutian , Ho Harrison , Liu Fengchen , Chen Feng , Morgan-Kiss Rachael , Shi Lizhen , Liu Han , Wang Zhong
Published: February 2025

Genome foundation models hold transformative potential for precision medicine, drug discovery, and understanding complex biological systems. However, existing models are often inefficient, constrained by suboptimal tokenization and architectural design, and biased toward reference genomes, limiting their representation of low-abundance, uncultured microbes in the rare biosphere. To address these challenges, we developedGenomeOcean, a 4-billion-parameter generative genome foundation model trained on over 600 Gbp of high-quality contigs derived from 220 TB of metagenomic datasets collected from diverse habitats across Earth’s ecosystems. A key innovation of GenomeOcean is training directly on large-scale co-assemblies of metagenomic samples, enabling enhanced representation of rare microbial species and improving generalizability beyond genome-centric approaches. We implemented a byte-pair encoding

(BPE) tokenization strategy for genome sequence generation, alongside architectural optimizations, achieving up to 150× faster sequence generation while maintaining high biological fidelity. GenomeOcean excels in representing microbial species and generating protein-coding genes constrained by evolutionary principles. Additionally, its fine-tuned model demonstrates the ability to discover novel biosynthetic gene clusters (BGCs) in natural genomes and perform zero-shot synthesis of biochemically plausible, complete BGCs. GenomeOcean sets a new benchmark for metagenomic research, natural product discovery, and synthetic biology, offering a robust foundation for advancing these fields.
The imbalance of nature: The Role of Species Environmental Responses for Ecosystem Stability
Authors: Polazzo Francesco , Hämmig Til , Petchey Owen L. , Pennekamp Frank
Published: February 2025

Understanding the mechanisms underlying ecosystem stability is crucial in predicting ecological responses to environmental fluctuations. While the diversity-stability relationship has been widely studied, the role of species’ fundamental responses to the environment remains underexplored. Here, we investigate how the distribution of fundamental responses, captured by a novel metric—imbalance—drives ecosystem stability through asynchrony and population stability. Using a microcosm experiment with protist communities, we manipulated species richness and response distributions (defined as interspecific variation in species performance curves) under fluctuating temperature and different nutrient concentrations. Our results show that lower imbalance, achieved through asynchrony or high population stability, causes higher temporal stability, while richness has no effect on stability. Structural equation modelling revealed that imbalance decreases stability indirectly via increasing synchrony and decreasing population stability, explaining 90% of observed variation. Comparing imbalance derived from single versus multispecies communities demonstrates that fundamental species responses are primary drivers of stability, challenging traditional paradigms emphasizing interspecific interactions. This study provides mechanistic links between species’ responses, environmental variability, and ecosystem stability, offering new insights into the responses of ecological systems to environmental change.
Unravelling epigenetic regulation of gene expression with explainable AI - a case study leveraging degron data
Authors: Chhatbar Kashyap , Bird Adrian , Sanguinetti Guido
Published: February 2025

Transcriptional regulation involves complex interactions involving chromatin–associated proteins, but disentangling these mechanistically remains challenging. Here, we generate deep learning models to predict RNA Pol–II occupancy from chromatin–associated protein profiles in unperturbed conditions. We evaluate the suitability of Shapley Additive Explanations (SHAP), a widely used explainable AI (XAI) approach, to infer causality and analyse regulatory mechanisms across diverse datasets and to validate these insights using data from degron–based perturbation experiments. Remarkably, genes ranked by SHAP importance predict direct targets of perturbation even from unperturbed data, enabling inference without costly experimental interventions. Our analysis reveals that SHAP not only predicts differential gene expression but also captures the magnitude of transcriptional changes. We validate the cooperative roles of SET1A and ZC3H4 at promoters and distinct regulatory contributions of ZC3H4 at gene bodies in influencing transcription. Cross-dataset validation uncovers unexpected connections between ZC3H4, a component of the Restrictor complex, and INTS11, part of the Integrator complex, suggesting crosstalk mediated by H3K4me3 and the SET1/COMPASS complex in transcriptional regulation. These findings highlight the power of integrating predictive modelling and experimental validation to unravel complex context-dependent regulatory networks and generate novel biological hypotheses.
ggRibo: a ggplot-based single-gene viewer for visualizing Ribo-seq and related omics datasets
Authors: Wu Hsin-Yen Larry , Kaufman Isaiah D. , Hsu Polly Yingshan
Published: February 2025

Visualizing periodic Ribo-seq data within genes of interest is a powerful approach to studying mRNA translation, but its application is limited by a lack of robust tools. Here, we introduceggRibo, a user-friendly R package for visualizing individual gene expression, integrating Ribo-seq, RNA-seq, and other genome-wide datasets with flexible scaling options.ggRibopresents the 3-nucleotide periodicity, a hallmark of translating ribosomes, within a gene-structure context, including introns and untranslated regions, enabling the study of novel ORFs, isoform translation, and mechanisms of translational regulation.ggRibocan plot multiple Ribo-seq/RNA-seq datasets from different conditions for comparison. Additionally, it supports the visualization of other omics datasets that could also be presented with single-nucleotide resolution, such as RNA degradome, transcription start sites, and translation initiation sites. Through its intuitive and flexible platform,ggRiboenables parallel comparisons of multi-omic datasets, facilitating a comprehensive understanding of gene expression regulation and promoting hypothesis generation. We demonstrate its utility with examples of upstream ORFs, downstream ORFs, isoform translation, and multi-omic comparison in humans and Arabidopsis. In summary,ggRibois an advanced single-gene viewer that enhances the interpretation of translatome and related genome-wide datasets, offering a valuable resource for studying gene expression regulation.ggRibois available on GitHub (https://github.com/hsinyenwu/ggRibo).
Strange effects of activation dynamics on musculoskeletal trajectory optimization
Authors: van den Bogert Antonie J. (Ton)
Published: February 2025

Muscle activation dynamics is usually described with a nonlinear differential equation, such that the activation occurs faster than deactivation. When a muscle excitation input switches rapidly between two values, this produces a “pumping” effect that raises the activation above the mean excitation input. This effect will favor rapid switching strategies when excitation is used in the optimization objective for human movement. The optimal strategy has infinitely fast switching, and is difficult to obtain with direct collocation methods. This problem can be eliminated by using activation, rather than excitation, in the optimization objective.
HSP70 is a chaperone for IL-33 secretion and function in chronic airway disease
Authors: Osorio Omar A. , Kluender Colin E. , Raphael Heather E. , Hassan Ghandi F. , Cohen Lucy S. , Steinberg Deborah F. , Payne Morgan D. , Luo Ethan M. , Hicks Jamie L. , Katz-Kiriakos Ella , Byers Derek E. , Alexander-Brett Jennifer
Published: February 2025

Rationale

IL-33 is a key driver of type 2 inflammation relevant to airway epithelial biology. However, the mechanisms for IL-33 secretion and regulation in the context of chronic airway disease is poorly understood.

Objectives

We sought to define how a disease associated isoform IL-33Δ34that escapes nuclear sequestration and is tonically secreted from epithelial cells can be recruited to non-canonical secretory pathways.

Methods

IL-33Δ34interaction with HSP70 was assessed and validated by affinity purification, mass-spectrometry and miniTurboID proximity labeling. Secretion and activity reporter assays were used to probe the effect of HSP70 on epithelial IL-33Δ34secretion and receptor binding. Human airway disease biospecimens were analyzed for dysregulation of heat shock pathways revealing modulation of TCP1 complex intermediates.

Measurements and Main Results

We confirmed that HSP70 interacts directly with IL-33Δ34, recruits the cytokine to a vesicular compartment and enhances stability upon secretion. IL-33, HSP70 and other key mediators of proteostasis were found to be dysregulated in airway disease biospecimens and secreted extracellular vesicles. The IL-33Δ34interactome was characterized and novel secretion modulators were identified.

Conclusions

This study confirms a role for HSP70 in non-canonical IL-33Δ34secretion and function that may be amenable for therapeutic targeting in airway diseases.
HIDE: Hierarchical cell-type Deconvolution
Authors: Völkl Dennis , Mensching-Buhr Malte , Sterr Thomas , Bolz Sarah , Schäfer Andreas , Seifert Nicole , Tauschke Jana , Rayford Austin , Straume Oddbjørn , Zacharias Helena U. , Grellscheid Sushma Nagaraja , Beissbarth Tim , Altenbuchinger Michael , Görtler Franziska
Published: February 2025

Motivation

Cell-type deconvolution is a computational approach to infer cellular distributions from bulk transcriptomics data. Several methods have been proposed, each with its own advantages and disadvantages. Reference based approaches make use of archetypic transcriptomic profiles representing individual cell types. Those reference profiles are ideally chosen such that the observed bulks can be reconstructed as a linear combination thereof. This strategy, however, ignores the fact that cellular populations arise through the process of cellular differentiation, which entails the gradual emergence of cell groups with diverse morphological and functional characteristics.

Results

Here, we propose Hierarchical cell-type Deconvolution (HIDE), a cell-type deconvolution approach which incorporates a cell hierarchy for improved performance and interpretability. This is achieved by a hierarchical procedure that preserves estimates of major cell populations while inferring their respective subpopulations. We show in simulation studies that this procedure produces more reliable and more consistent results than other state-of-the-art approaches. Finally, we provide an example application of HIDE to explore breast cancer specimens from TCGA.

Availability

A python implementation of HIDE is available at zenodo (doi:10.5281/zenodo.14724906).

Supplementary information

Supplementary material is available atBioinformaticsonline.
VegVault database: linking global paleo-, and neo-vegetation data with functional traits and abiotic drivers
Authors: Mottl Ondrej , Gaiser Franka , Simova Irena , Flantua Suzette
Published: February 2025

Understanding the dynamics and persistence of biodiversity patterns over short (present) and long (thousands of years) time scales is crucial for predicting ecosystem changes under global climate and land-use changes. A key challenge is integrating currently scattered ecological data to assess complex vegetation dynamics over time. Here, we present VegVault, an interdisciplinary SQLite database that uniquely integrates paleo- and neo-ecological plot-based vegetation data on a global and millennial scale, directly linking them with functional traits, soil, and climate information. VegVault currently comprises data from BIEN, sPlotOpen, TRY, Neotoma, CHELSA, and WoSIS, providing a comprehensive and ready-to-use resource for researchers across various fields to address questions about past and contemporary biodiversity patterns and their abiotic drivers. To further support usability of the data, VegVault is complemented by the {vaultkeepr} R package, enabling streamlined data access, extraction, and manipulation. This study introduces the structure, content, and diverse applications of VegVault, emphasizing its role in advancing ecological research to improve predictions of biodiversity responses to global climate change.
MDSC depletion during immunization with heat-killedMycobacterium tuberculosisincreases protection against BCG infection
Authors: Aintablian Arpa , Alattar Haisam , Cyran Laura , Schoen Christoph , Du Plessis Nelita , Walzl Gerhard , Schaible Ulrich , Nieuwenhuizen Natalie E. , Lutz Manfred B.
Published: February 2025

Tuberculosis (TB) is still one of the deadliest infectious diseases globally. Although i.d. BCG immunization offers limited protection, a vaccine based onMycobacterium tuberculosis(Mtb) has yet to be approved. Our previous findings demonstrated that s.c. immunization with heat-killed Mtb significantly increased the number of monocytic myeloid-derived suppressor cells (M-MDSC) in mice. Therefore, we hypothesized that the defense against a subsequent BCG infection would be impaired in Mtb-immunized mice. Surprisingly, mice vaccinated with Mtb were protected against a BCG infection and showed elevated frequencies and activation of DC and mycobacteria-specific T cells despite high frequencies and suppressor activity of M-MDSC. Genetic ablation of CCR2+monocytic cells or pharmacological intervention with all-trans retinoic acid (ATRA) reduced the frequency of Mtb-induced M-MDSC, enhanced frequencies, and activation of dendritic cells (DC) and CD4+T cells, and resulted in decreased bacterial loads in the lung and spleen. These findings offer fresh perspectives on TB vaccination using heat-killed Mtb despite parallel unwanted vaccine-induced M-MDSC. M-MDSC depletion by ATRA further tips the balance towards immunity and should be considered an adjunct host-directed therapy with TB vaccines in humans.
Impact of mating strategies on life-history traits in the alien land snailRumina decollata
Authors: Pizá Julia , Cifola Lara , Perl Melisa , Abafatori Matías , Bonel Nicolás
Published: February 2025

Abstract

Climate change and global transport are driving species introductions worldwide, leading to economic and ecological consequences. Hermaphroditic organisms are able to reproduce with any conspecific, and some can self-fertilize, enhancing their potential for population establishment despite low initial densities in colonization events. This study examines how mating strategies influence the life history traits of the alien land snailRumina decollataby comparing individuals subjected to facultative cross-fertilization or enforced self-fertilization over two laboratory-reared generations. Key life history traits—including size and age at first reproduction, fecundity, hatching time, and juvenile survival—were measured, alongside individual growth and shell morphometry. Self-fertilizing individuals exhibited higher body weight at first clutch but lower fecundity and delayed reproduction compared to cross-fertilizers. Selfing offspring (F2) took longer to hatch and had lower survival rates, indicating significant inbreeding depression. Selfed snails of F1grew faster than outcrossers, but experienced a decline in growth in F2, consistent with inbreeding depression. Conversely, shell shape remained similar between mating treatments. Although selfing imposed fitness costs, 32% of self-fertilizing individuals produced viable offspring, highlighting their ability to establish in new environments. This study improves our understanding of howR. decollata’s reproductive strategies shape life history traits under environmental constraints.

SIMPLE SUMMARY

Species are spreading to new regions due to climate change and global transport, often causing environmental and economic challenges. Hermaphrodite species that can reproduce by cross or self-fertilization can establish populations even when few individuals are present. In our study, we examined how these two reproductive strategies affect a land snail’s growth, reproduction, and survival. We found that self-fertilizing snails grew larger and heavier but laid fewer eggs and reproduced later than those that mated with others. Additionally, their offspring took longer to hatch and had lower survival rates. These results suggest that self-fertilization comes with costs, likely due to inbreeding depression, but it still allows the species to establish in new environments. Despite lower survival, one-third of the self-fertilizing snails produced viable offspring, showing that this strategy can support population growth when mates are scarce. As this species continues to expand into new areas, our findings help explain how it adapts to different environments. Understanding these reproductive strategies is important for predicting its spread and managing its potential impact on ecosystems.
Comparative Extraction of Cellular Features from High-Resolution Volume Imaging
Authors: Mimori-Kiyosue Yuko , Hamaji Tomoko , Hayashi Akiko , Okada Miwa , Higasa Koichiro , Kiyosue Kazuyuki , Gomibuchi Yuki , Yasunaga Takuo , Washio Takashi , Hara Satoshi
Published: February 2025

High-resolution volume imaging techniques, such as lattice light-sheet microscopy (LLSM), generate vast and complex datasets that demand advanced analytical approaches to uncover biologically meaningful insights. While LLSM’s high spatial and temporal resolution provides critical data for understanding cellular processes, distinguishing subtle differences between cells in distinct states remains challenging. Here, using an adaptive, human-interpretable kernel-based calculation strategy, we developed Machine-Learning-Based Visual Extraction of Structural Features (M-VEST), a method designed to identify and interpret structural differences with high precision. By applying M-VEST to mitotic cells, we uncovered novel functions of the oncogene Aurora kinase A, demonstrating its utility in revealing previously undetected features. Validated using LLSM datasets, M-VEST offers a scalable framework for analyzing large and complex imaging data, advancing insights into cellular dynamics and beyond.
Quantifying the impact of genetic determinants of antibiotic resistance on bacterial lineage dynamics
Authors: Helekal David , Mortimer Tatum D. , Mukherjee Aditi , Palace Samantha G. , Grad Yonatan H.
Published: February 2025

The dynamics of antimicrobial resistance in bacteria are informed by the fitness advantages conferred by genetic determinants of resistance in the presence of antibiotic pressure and the potential fitness costs in its absence. However, frameworks for quantitative estimates of real-world fitness impact have been lacking, given multidrug resistance, multiple pathways to resistance, and uncertainty around drug exposures. Here, we addressed these challenges through analysis of genome sequences from clinical isolates ofNeisseria gonorrhoeaecollected over 20 years from across the United States, together with national data on antibiotic treatment. Using a hierarchical Bayesian phylodynamic model, we quantified the contributions of resistance determinants to strain success. Resistance mutations had a fitness benefit when the cognate antibiotic was in use but did not always incur a fitness cost otherwise. Two fluoroquinolone-resistance conferring mutations at the same site ingyrAhad divergent fitness impact after fluoroquinolones were no longer used for treatment, findings supported byin vitrocompetition experiments. Fitness costs were alleviated by loss of costly resistance determinants and counterbalanced by gain of new fitness-conferring resistance determinants. Quantifying the extent to which the resistance determinants explained each lineage’s dynamics highlighted gaps and pointed to opportunities for investigation into other genetic and environmental drivers. This work thus establishes a method for linking pathogen genomics and antibiotic use patterns to quantify the fitness impact of resistance determinants and the factors shaping ecological trends.
Early life adversity and White Matter Microstructural Organization - a systematic review
Authors: Mitchell Orla , Roddy Darren W , Connaughton Michael
Published: February 2025

Early life adversity, defined as exposure to stressful events during childhood, is a significant risk factor for the development of psychiatric disorders. Diffusion tensor imaging studies employing tract-based spatial statistics have shown microstructural abnormalities in white matter among individuals exposed to early life adversity; however, robust conclusions are yet to be drawn. This systematic review synthesizes findings of previous tract-based spatial statistics studies to identify the white matter alterations in adult brains exposed to early life adversity, in papers with methodological consistency. The literature search (April 2024) was conducted to identify tract-based spatial statistics studies that compared diffusion metrics between adults exposed to early life adversity and adults not. Embase, Pubmed, and PsycInfo were searched, retrieving 2458 articles. Following deduplication, 1739 titles and/or abstracts were screened. 1699 articles were excluded, and 40 full texts were reviewed. Seven articles, reporting on 764 subjects, met the inclusion criteria and were included in the narrative synthesis. Compared to controls, adults exposed to early life adversity showed lower fractional anisotropy values in white matter tracts of the limbic and visual processing systems, specifically the anterior thalamic radiation, inferior longitudinal fasciculus, corona radiata, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum bundle. This systematic review highlights that early life adversity may underlie emotional dysregulation and contribute to an increased risk of psychopathology in later life and explores the potential neurobiological mechanisms that underpin these structural changes. Understanding these associations is crucial for developing targeted interventions aimed at mitigating the long-term impact of early life adversity.
Inferring binding rates from enzymatic turnover time statistics
Authors: Singh Divya , Urbakh Michael , Reuveni Shlomi
Published: February 2025

We present a method to extract enzyme-substrate binding rates from observations of enzymatic turnover times. Our approach involves segregating the short-time statistics of the turnover time distribution and inferring from it the binding rate in a general and robust manner. Beyond determining binding rates, the approach developed herein also allows us to infer: (i) the fertile collision probabilityp, i.e., the probability that a collision between an enzyme and a substrate will result in the formation of an enzyme-substrate complex; and (ii) the fertile catalysis probabilityϕcat, i.e., the probability that the enzyme-substrate complex will lead to the formation of a product. It has long been known thatpϕcat≪ 1, indicating that most enzymes operate far from maximal efficiency, yet separating the contributions of fertile binding and catalysis was not possible in lieu of direct binding rate measurements. Our method overcomes this limitation by enabling precise inference of binding rates from turnover times, which in turn opens the door for a more detailed understanding of enzymatic efficiency.
The mechanics of a continuous self-assemblingsurface-layer aids cell division in an archaeon
Authors: Foo Sherman , Caspy Ido , Cezanne Alice , Bharat Tanmay A.M. , Baum Buzz
Published: February 2025

The surface layer or “S-layer” is a planar lattice of glycosylated proteins that coats a wide range of archaea and bacteria instead of a classical cell wall or capsular polysaccharides, insulating them from the extracellular space and providing the cell membrane with physical support. Although the S-layer’s role as a mechanical support for the membrane might be expected to hinder cell division, we show that in rapidly dividingSulfolobus acidocaldariuscells, the S-layer protein SlaA self-assembles into flexible lattice that helps flattens the cytokinetic furrow to accelerate ESCRT-III dependent cell division - a role that is especially important under conditions of mechanical stress. Taken together, these results generated using mutational analysis, live and fixed cellular imaging, along with electron cryomicroscopy, define the rules governing S-layer self-assembly and show how the mechanical properties of flexible lattice coats can enhance membrane functions to both physically support a cell and help to drive ESCRT-III dependent cell division.

Significance statement

The bounding membrane of a cell must be protected from environmental insults. In many bacteria and archaea that lack a cell wall, this is achieved by an enveloping S-layer. By virtue of its rigid, planar structure, the S-layer is also expected to act as a barrier to the cell shape changes required for cytokinesis. In this study of the S-layer lattice in the archaeonSulfolobus acidocaldariushowever, we demonstrate a role for this self-assembling mechanical support in re-shaping the cytokinetic furrow as an aid to ESCRT-III-mediated division. In showing how mechanically active and passive structures can work together to give rise to mechanically stable cells that can divide, this reconciles what seems like a trade-off between resilience and flexibility.
Th1 and Th2 cytokines profile of serum samples from dengue positive cases from Northeast India
Authors: Singh Kiran , Bhattacharya Shinjini , Sharma Ajanta , Kumar Sachin
Published: February 2025

Background: Dengue fever is a fast-spreading acute arboviral infection transmitted by a human-Aedes mosquito cycle. Northeastern India is an endemic zone for dengue; regular outbreaks have been reported. However, molecular details of the virus infection in the host have not been established. Studies on dengue immunopathogenesis have primarily utilized data from American and Southeast Asian regions, with insufficient representation from India. Objective: The present study aimed to characterize the Th1/Th2 cytokine expression profiles from dengue cases in different parts of northeastern India. Statistical analysis cum Results: Among the panel of Th1/Th2 cytokines, IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-13, and TNF-α cytokines are found to be higher in dengue-infected patients. Anti-inflammatory cytokines are somehow regulated differently in male-female patients. Conclusion: This clinical study on dengue patient samples for cytokine profiling revealed distinct cytokine patterns and their regulation, but further investigation is needed to correlate with disease severity to identify potential biomarkers for disease progression.
Programmedin vivoexcision of prophage Φ13 is an essential timing device for theStaphylococcus aureusinfectious process
Authors: Poupel Olivier , Kenanian Gérald , Touqui Lhousseine , Abrial Charlotte , Msadek Tarek , Dubrac Sarah
Published: February 2025

Mobile genetic elements play an essential part in the infectious process of major pathogens, yet the role of prophage dynamics inStaphylococcus aureusremains poorly understood. Here we studied the impact of the Φ13hlb-converting prophage, whose integration inactivates thehlbβ-toxin gene, on staphylococcal pathogenesis. We showed that prophage Φ13 is lost in approximately half the bacterial population during the course of infection. Inactivation of the Φ13intrecombinase gene, essential for insertion/excision, locked the prophage in the bacterial chromosome, leading to a significant loss of virulence in a murine systemic infection model. In contrast, the non-lysogen strain (ΔΦ13), where thehlbbeta-hemolysin gene is reconstituted, displayed strongly increased virulence. Accordingly, histopathological analyses revealed more severe nephritis in mice infected with bacteria lacking prophage Φ13 (ΔΦ13), in contrast to infection with the parental strain and particularly with the Δintmutant, which led to less severe renal lesions. Cytokine induction in a human neutrophil model showed significantly increased IL-6 expression following infection with the beta-hemolysin producing strain (ΔΦ13). Our results indicate that programmedin vivoexcision of the Φ13 prophage is essential for progression of theStaphylococcus aureusinfectious process, since early excision rapidly kills the host whereas the absence of excision significantly lowers staphylococcal virulence.

IMPORTANCE

This study highlights prophage Φ13 excision as a critical factor inS. aureuspathogenesis, influencing infection outcomes by balancing rapid host killing with reduced bacterial virulence. This mechanism may represent a bet-hedging strategy in genetic regulation, resulting in a mixed bacterial population capable of rapidly switching between two processes: bacterial colonization and host damage. Unraveling this dynamic opens new possibilities for developing targeted therapies to disrupt or modulate prophage activity, offering a novel approach to mitigatingS. aureusinfections.
Axon collateral pattern of a sparse locus coeruleus norepinephrine neuron in mouse cerebral cortex
Authors: Wu Yu-Ming , Hung Wei-Chen , Chang Yun , Min Ming-Yuan , Yang Hsiu-Wen
Published: February 2025

The locus coeruleus (LC) contains predominantly norepinephrine (NE) neurons with widespread axonal projections throughout the brain and plays a critical role in the control of behavior, particularly arousal. Historically, the LC-NE system was thought to perform this function by releasing NE uniformly throughout most brain regions. However, recent evidence suggests that the cortical projections of the LC are modularly organized, allowing coordination of diverse and sometimes opposing functions, such as fear memory formation and extinction. However, many details remain unclear, and answers require data from axon collaterals of sparse neurons. We modified a viral tracing protocol using a dual recombinase system to trace the axonal collaterals of sparse LC neurons projecting to the cingulate cortex (CgC). Our results show that even a small number of LC neurons still have broad cortical projections, but the pattern is not uniform. There are a few major projections with dense fibers and numerous minor projections with sparse innervation. Notably, the major projections, including the rostrosplenial cortex, dorsal hippocampus, somatosensory cortex, and CgC (the injection site for retrograde viral labeling), are functionally related and may coordinate goal-directed navigation. In conclusion, our results suggest that a single LC neuron projects divergently and non-uniformly to the cortex, with major projections coordinating related cortical areas to regulate specific functions, while minor projections appear less functionally specific. It’s likely that each LC-NE neuron plays a role in maintaining arousal through the minor projections.
In silicoclassification and identification co-purified protein complexes yield new structures and multiple MSP assembly states
Authors: Zhang Qingyang , Murthy Abhinandan Venkatesha , Mim Carsten
Published: February 2025

Native protein complexes have garnered interest as targets for structural dissemination. Cryogenic electron microscopy (cryoEM) with its ability to image protein mixtures is the most promising tool to enable structural proteomics. Additionally, image processing has evolved to deal with conformational and compositional heterogeneity. Integrative approaches, namely mass spectrometry in conjunction with cryoEM have made it possible to characterize and identify complex mixtures. However, this comes at a cost of generating models and interpreting mass spectra. Here we present a modified approach that only requires electron micrographs and a computer for unsupervised model building and protein identification. We were able to identify co-purified membrane proteins, resulting in a novel structure and unexpected nanodisc assemblies, which imply direct interaction between membrane proteins and membrane scaffolding proteins.
Maturation-dependent complement production and C3 processing in human retinal pigment epithelium cells
Authors: Schikora Juliane , Nickel Antonia , Bergert Jasmin , Hähnel Rike , Dort Aaron , Schayan-Araghi Stella Y. , Banerjee Pratiti , Wolf Hannah N. , May-Simera Helen , Pauly Diana
Published: February 2025

Induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells, closely resembling healthy RPE, offer valuable insights for retinal disease modelling. This study evaluates immature and mature phenotypes of iPSC-RPE and ARPE-19 cells, comparing RPE characteristics, cell-associated complement profiles, and TGF-β1-mediated stress responses across transcript expression, secretion, and protein levels. Statistical analyses were performed using independent meanst-test and Wilcoxon rank-sum test. Mature iPSC-RPE cells exhibited characteristic RPE-morphology, with elevated secretion of complement components (C3, FH/FHL-1, FI), unique FB secretion, and apical complement localisation. Intracellular C3 processing revealed cleavage products different from known blood-derived C3 fragments and showed maturation-dependent differences; only mature iPSC-RPE cells secreted active C3 forms (C3(H2O), C3a) and exhibited the intact C3 β-chain. Mature ARPE-19 and iPSC-RPE cells demonstrated resistance to TGF-β1 treatment, which reduced complement secretion without affecting C3a release. In conclusion, ARPE-19 and iPSC-RPE cells demonstrated local production of complement components and maturation-dependent intracellular processing of C3 into active forms. These findings highlight the impact of RPE maturation on local C3 activation, providing a basis for future studies on C3 functionality in the RPE and its potential pathological effects.

Impact statement

Cell state-dependent local processing of complement C3 in retinal pigment epithelium cells generates active C3 forms that may evade anti-C3 therapies, influencing age-related macular degeneration and treatment outcomes.

Funding statement

This project has received funding from the PRO RETINA, Amberg, Germany, under grant agreement number “Pro-Re/Projekt/Schikora – Pauly.05-2022”, and Deutsche Forschungsgemeinschaft (DFG), under grant agreement number “498244102 (MA 6139/5-1)“. Open access funding provided by the Open Access Publishing Fund of University Marburg. Funding sources were not involved in study design, data collection and interpretation, or the decision to submit the work for publication.

Graphical abstract
Sensitivity and control of a six-axis fused-silica seismometer
Authors: Smetana Jiri , Ubhi Amit Singh , Chick Emilia , Prokhorov Leonid , Bryant John , Dmitriev Artemiy , Gill Alex , Koponen Lari , Martynov Denis , Miao Haixing , Cumming Alan V. , Hammond Giles , Frolov Valery , Mittleman Richard , Fritchel Peter
Published: February 2025

We present a pair of seismometers capable of measurement in all six axes of rigid motion. The vacuum-compatible devices implement compact interferometric displacement sensors to surpass the sensitivity of typical electrical-readout schemes. Together with the capability to subtract the sensitivity-limiting coupling of ground tilt into horizontal motion, our seismometers can widen the sensing band toward megahertz frequencies. This has notable applications across a range of fields requiring access to low-frequency signals, such as seismology and climate research. We particularly highlight their potential application in gravitational-wave observatories (the Laser Interferometer Gravitational-Wave Observatory, LIGO) in improving their observation capability of intermediate-mass black holes (approximately 1000M⊙). The sensors are based on a near-monolithic fused-silica design consisting of a fused-silica mass and fiber, showing improved stability and robustness to tilt drifts, alignment, and control compared to all-metal or mixed metal-silica designs. We demonstrate tilt sensitivity that surpasses the best commercial alternatives in a significantly reduced footprint compared to our previous iterations of these sensors.

Published by the American Physical Society
2025
Kohlrausch regime of slow relaxation and its phenomenology in isolated quantum many-body systems with strong disorder
Authors: Haldar Asmi
Published: February 2025

The Kohlrausch(-Williams-Watts) law of stretched exponential relaxation has been observed for over a century and a half in diverse complex classical systems. Here we show that this law describes relaxation quite generically in closed (executing Schrödinger dynamics), interacting disordered many-body systems, using interaction range and disorder strength as primary tuning parameters. This we observe for both time-independent and periodically driven (Floquet) systems. Finite-size analysis indicates the persistence of this nonthermal relaxation regime in the thermodynamic limit thus defining a distinct dynamical regime. This regime exhibits a peak in the time scale of the long-time relaxation (following a transient), upon crossing over from weak to strong disorder. We provide a simple picture of this behavior, which naturally accounts for its generic occurrence. Formation of spin-glass — one of the possible mechanisms for stretched relaxation appears incidental to the occurrence of Kohlrausch law in our context. Finally, we provide a simple non-Hermitian Hamiltonian formulation for the dynamics of a single spin embedded in the disordered chain. This provides an analytical formula that captures not only the Kohlrausch relaxation of the disorder averaged autocorrelation but also captures the largely diverse dynamics of an arbitrary target spin in the system. Our work hence also provides a concrete quantification of the “prethermal slowness” in many-body disordered system.

Published by the American Physical Society
2025
Vacuum transitions with the Gauss-Bonnet term in
D
dimensions
Authors: Liu Yang
Published: February 2025

In our previous paper [; ], we proposed a probabilistic argument to explain the reason why the cosmological constant is very small in 4D. We can ask a question: if the behavior of tunneling exponent B can be generalized to D-dimension. Moreover, in higher dimensional theory motivated by string theory the Gauss-Bonnet term plays an important role. Therefore, in this paper, we generalize our result in previous paper [; ] to arbitrary D dimensions including the Gauss-Bonnet term. As a result, we have two main results. We find that the Euclidean action of the bounce, B, describing the decay of a de Sitter vacuum, is proportional to k+−(D−2), which has a pole as k+2→0 where k+2 is the curvature of the parent vacuum. This result is similar to the result in 4D. The other result is that we find a new decay channel, describing up-tunneling from anti–de Sitter into de Sitter. The meaning of this new decay channel in the string landscape should be explored in the future.

Published by the American Physical Society
2025
Diminishing effect of a pressure gradient on large-scale rolls of plane Couette flow: A singular value analysis
Authors: Dokoza Toni , Hennings de Lara Joao Vinicius , Oberlack Martin
Published: February 2025

We investigate the transition from pure Couette flow to Poiseuille flow at Re≈2250 with a focus on the observed disappearance of single-circle coherent structures occupying the whole channel height. According to the DNS study by Gandía-Barberá [], these are accompanied by a change of sign in the Reynolds stress tensor at sufficiently large pressure gradients, although from a deeper theoretical point of view the actual mechanisms for the disappearance of these structures remained completely uncovered. In order to investigate the behavior of these structures theoretically, we use resolvent and structured singular value analysis, with the aforementioned DNS serving as a data basis for comparison, hence simultaneously exploring the capabilities of resolvent and structured singular value analysis in capturing the characteristics of these structures. Through detailed parameter studies, we examine how the pressure gradient influences the length and width of streamwise elongated rolls, noting a shortening and narrowing effect as the flow becomes increasingly pressure driven, and compare these effects to the ones observed in the DNS work. Additional insights into the development of coherent structures are gained, as their wall-normal positions are successfully linked to the occurrence of critical layers within the flow, particularly through structured singular value analysis. The results show that the modified response modes from structured singular value analysis show the best agreement with the DNS observations, suggesting that these analytical approaches can effectively replicate the phenomena otherwise obtained only through costly DNS, and provide deeper insights into the underlying fluid dynamics.

Published by the American Physical Society
2025
Dichroic mirror pulses for optimized higher-order atomic Bragg diffraction
Authors: Pfeiffer D. , Dietrich M. , Schach P. , Birkl G. , Giese E.
Published: February 2025

Increasing the sensitivity of light-pulse atom interferometers progressively relies on large-momentum transfer techniques. Precise control of such methods is imperative to exploit the full capabilities of these quantum sensors. One key element is the mitigation of deleterious effects such as parasitic paths deteriorating the interferometric signal. In this Letter, we present the experimental realization of dichroic mirror pulses for atom interferometry, its scalability to higher-order Bragg diffraction, and its robustness against initial momentum spread. Our approach selectively reflects resonant atom paths into the detected interferometer output, ensuring that these contribute to the signal with intent. Simultaneously, parasitic paths are efficiently transmitted by the mirror and not directed to the relevant interferometer outputs. This method effectively isolates the desired interferometric signal from noise induced by unwanted paths. It can be readily applied to existing setups capable of higher-order Bragg diffraction.

Published by the American Physical Society
2025
Cost-sensitive feature selection for multi-label classification: multi-criteria decision-making approach
Authors: Mohanrasu S.S. , Phan Le Thi , Rajan Rakkiyappan , Manavalan Balachandran
Published: February 2025

Purpose

In multi-label classification, selecting the most relevant features is crucial for enhancing predictive performance and reducing computational complexity. Real-world scenarios often involve significant costs in data acquisition, including time, financial and computational resources. However, most existing feature selection methods overlook the associated costs.

Design/methodology/approach

Multicriteria decision-making (MCDM) has emerged as a powerful tool for addressing complex problems involving multiple, often conflicting criteria. This study proposes a novel cost-sensitive multi-label feature selection method that fuses feature importance with feature cost within an MCDM framework. The proposed method transforms a cost-sensitive multi-label feature selection problem into an MCDM problem by leveraging mutual information. Furthermore, the data were converted into Fermatean fuzzy sets, and the Fermatean fuzzy simple weighted sum product (WISP) method was employed to rank features based on their relevance to labels and associated costs.

Findings

Extensive experiments conducted on ten benchmark datasets against five evaluation metrics demonstrated the superiority of the proposed method in selecting relevant features while minimizing costs and consistently outperforming existing methods.

Originality/value

Unlike existing methods that integrate costs through penalties and select features via a greedy search, the proposed approach adopts an MCDM-based strategy for feature ranking. This method aims to achieve globally optimal outcomes by balancing the trade-offs between conflicting objectives, marking a significant advancement over existing techniques.

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