bluuebunny/crossref_metadata_2025 huggingface dataset:
TaWUS2D regulates the number of grains per spikelet by enhancing the number of fertile ovaries in Multi-Ovary Wheat
Authors: Schoen Adam William , Sharma Parva Kumar , Mahlandt Alex , Chen Andy , Sheng Huajin , Kochian Leon , Gao Peng , Xiang Daoquan , Quilichini Teagen , Venglat Prakash , Wang Sheng , Yadav Inderjit Singh , Gu Yong , Rodriguez-Leal Daniel , Luo Weifeng , Qi Yiping , Meier Nathan , Kajla Anmol , Willman Matthew , Brown-Guedira Gina , Youngblood Cal , Hulse-Kemp Amanda , Murphy Angus , Gill Bikram , Uauy Cristobal , Datla Raju , Rawat Nidhi , Tiwari Vijay
Published: February 2025

Innovative genetic improvements in the staple crop Triticum aestivum (bread wheat) are urgently needed to address the growing global food security crisis. Here, we report the map-based cloning of TaWUS2D, the gene responsible for the dominant multi-ovary phenotype in wheat. Multi-ovary lines are characterized by the development of three fertile ovaries per floret that results in three grains, as opposed to wildtype single ovary wheat. We used HiFi long-reads to assemble a 14.48 Gbp genome scaffold assembly in the background of mutli-ovary wheat line MOV. Using high-resolution genetic mapping, combined with additional genomic resources, we defined the Mov-1 locus to a 135 Kbp region containing two genes. Using five independent deletion mutants and eight TILLING mutants, we demonstrate that a functional WUSCHEL-like protein, TaWUS2D, is required for the multi-ovary phenotype. TaWUS2D is upregulated in the MOV genetic background. This research lays the groundwork for developing new approaches to improve wheat production potential and sustainability in the face of current and future global food challenges.
Testing a general theory for flowering time shift as a function of growing season length
Authors: Park John S. , Jackson John , Bergsten Anna , Ågren Jon
Published: February 2025

Understanding the effects of climate change on the evolution of phenological timing, such as start of flowering, is of major interest because phenology is critical for fitness of populations, and underpins many ecological dynamics. Much recent research has focused on the correlation between phenological timing and the arrival of spring. However, the evolutionarily optimal seasonal timing should depend also on the duration of the growing season, within which entire annual life cycles must unfold. Optimal energy allocation theory can explicitly address life-history scheduling in a seasonal environment, and be used to predict how scheduling should adaptively respond to seasonality shifts. Here we extend a seminal theoretical framework for perennial plant scheduling by Iwasa & Cohen (1989), and predict a specific nonlinear relationship between growing season length and optimal flowering time expressed as number of days after the start of the growing season. We tested and found strong support for thisa prioriprediction in two independent common-garden experiments with purple loosestrife (Lythrum salicaria) and European goldenrod (Solidago virgaurea) populations sampled along latitudinal gradients in Sweden. Climate warming is commonly associated with changes in both the start and the duration of the growing season. Considering both effects, our findings suggest that as springs start earlier and growing seasons lengthen, shifts in optimal flowering time expressed as calendar date may initially stall before accelerating, potentially explaining observed variation in phenological shifts across systems. More broadly, we show how mechanistic life history theory can advance understanding of phenological change beyond correlative conclusions.

SIGNIFICANCE STATEMENT

The optimal timing for a plant to flower depends both on when spring begins and on the total length of the growing season—both shifting with climate change. However, the adaptation of flowering time to changes in growing season length is much less explored than to an advancing spring. Building on existing theory, we predict a nonlinear relationship between growing season length and optimal flowering time. Data on two species (purple loosestrife and European goldenrod) grown in common gardens strongly support this prediction. Our results demonstrate why species can vary in their observed phenological responses to climate change. More broadly, we highlight the power of mechanistic life history theory for explaining and predicting phenological shifts.
AllMetal3D: joint prediction of localization, identity and coordination geometry of common metal ions in proteins
Authors: Dürr Simon L. , Rothlisberger Ursula
Published: February 2025

Nature uses a variety of metal ions as cofactors for specific tasks. The three main classes of metals in biological systems are alkali ions (e.g. sodium and potassium), alkaline earth ions (e.g. magnesium and calcium) as well as transition metal ions (e.g. zinc or iron and many others). To date no selective predictor to localize each of these metals in a given protein structure exists. Current methods require either preselecting a specific ion (e.g MIB2 (Lu et al., 2022), ESMBind (Dai et al., 2024) or AlphaFold3 (Abramson et al., 2024) or a location (MICShub et al. (2024)). In this work, we describe an extension of the recently introduced Metal3D framework (Dürr et al., 2023) that was originally trained on zinc sites to predict the location of all biologically relevant classes of metal ions as well as to classify their coordination geometry. Our model is the first of its kind and even outperforms Metal3D for the prediction of the location of Zn2+and generalizes well to the other metals in terms of location prediction as well as identity classification. Comparing the model to several other available tools such as MetalSiteHunter, AlphaFold3, MIC, MIB2 and MetalHawk highlights important shortcomings in these tools with respect to data bias, prediction of negative sites and selectivity. However, concerning coordination geometry prediction, similar to other work, we find that our method cannot accurately make correct classifications beyond the most common classes in natural proteins i.e. tetrahedral and octahedral arrangements. AllMetal3D is available as ChimeraX extension, standalone web app as well as python package:https://github.com/lcbc-epfl/allmetal3d
Increased contact between lipid droplets and mitochondria in skeletal muscles of male elite endurance athletes
Authors: Nielsen Joachim , Petersen Kristine Grøsfjeld , de Almeida Martin Eisemann , Shepherd Sam O. , Christensen Britt , Petersen Maria Houborg , Højlund Kurt , Ørtenblad Niels , Gejl Kasper Degn
Published: February 2025

Endurance athletes exhibit higher skeletal muscle mitochondrial and lipid droplet (LD) content compared to recreationally active individuals, along with greater whole-body oxygen uptake and maximal fat oxidation rates. In this study, we investigated if these differences manifest in a greater LD-mitochondria contact and how this may relate to the organelles’ size, shape, and numerical densities. We obtained skeletal muscle biopsies from 17 male elite triathletes and road cyclists and 7 recreationally active men. Using quantitative transmission electron microscopy, we found that the endurance athletes had 2-3-fold greater LD-mitochondria contact length than the recreationally active individuals. This was related to higher numerical densities of both mitochondria and LDs in the intermyofibrillar space. Adding data from untrained individuals with equally high intermyofibrillar LD density as the endurance athletes revealed a 24% greater LD-mitochondria contact length in the endurance athletes. We observed small trivial differences in the shape of both organelles between populations. However, large mitochondrial profiles were more elongated and irregular in shape compared to small mitochondrial profiles, while large LD profiles were more circular and less irregular than small LD profiles. Within the group of athletes, large intermyofibrillar LD profiles correlated with a high fraction of PLIN5-positive LDs and their maximal fat oxidation rate was positively associated with an interaction between the profile size of both intermyofibrillar LDs and mitochondria. In conclusion, male endurance athletes have a greater LD-mitochondria contact than recreationally active and untrained individuals. This muscular phenotype is restricted to the intermyofibrillar space and to fibres rich in mitochondria.
Lipopolysaccharides nanodiscs, a biomimetic platform to study bacterial surface
Authors: Massilia Abbas , Samantha Micciulla , Jean-Marie Teulon , Meriem Maalej , Macha Trembley , Roberta Marchetti , Antonio Molinaro , Michel Thépaut , Franck Fieschi , Jean-Luc Pellequer , Cédric Laguri
Published: February 2025

Lipopolysaccharides (LPS) are essential components of the outer membranes of Gram-negative bacteria, playing a crucial role in antimicrobial resistance, virulence, and the host’s immune response. Self-assembled particles displaying LPS are essential for biophysical studies addressing the behavior of bacterial surfaces under specific biomimetic conditions. Styrene-maleic acid (SMA) copolymers were employed to form LPS nanodiscs, either from extracted LPS or directly from purified outer membranes. These nanodiscs, derived from pathogenic O157:H7 or laboratoryE. colistrains, are well-defined in size and yield high-resolution nuclear magnetic resonance (NMR) spectra. They have been successfully used to investigate molecular recognition by a human C-type Lectin Receptor (CLR) of the immune system and interaction with polymyxin antibiotics using various biophysical methods. This study high-lights the significance of LPS nanodiscs as bacterial surface mimetics and opens promising avenues for further research into LPS structure and interactions. The ability to generate well-defined LPS nanodiscs offers a powerful tool for studying the molecular mechanisms underlying bacterial pathogenesis and immune response.
Binding Affinity Ranking at the Molecular Initiating Event (BARMIE): An open- source computational pipeline for ecological hazard ranking of endocrine disrupting chemicals
Authors: Calahorro Fernando , Fouladi Parsa , Pandini Alessandro , Khushi Matloob , Gaihre Yogendra , Bury Nic
Published: February 2025

One of the key challenges in ecological risk assessment lies in identifying the chemicals that pose the greatest threat and determining the species that are most vulnerable to their effects. Computational prediction of protein binding affinity can help in assessing the risk of chemicals to species. In this study we developed and validated an open-source tool called BARMIE (Binding Affinity Ranking at the Molecular Initiating Event) to rank chemical hazards and identify species that are most susceptible based on the binding affinity of the chemical to steroid receptor proteins. As an exemplar of BARMIE’s output we focus on 163 teleost fish glucocorticoid receptors (GRs) and the natural ligand cortisol and 10 synthetic glucocorticoid (GCs) drugs and five other potential chemical GR agonists. The hazard ranking is based on the likelihood that the chemicals with the highest binding affinity are likely to outcompete cortisol at the receptor binding site. In this analysis, halcinonide, a GC, was predicted to be the most hazardous based on its binding affinity and the superorder Protacanthopterygii species, including the Esociformes and Salmoniformes, were identified as the most vulnerable. This computational pipeline can be expanded to evaluate more chemicals, species, and proteins as part of an in silico chemical hazard assessment tool.
Condensin IDChas a Functional ATPase That is Required for X-Chromosome Dosage Compensation inC. elegans
Authors: Chawla Bahaar , Jatia Suchi , Sloan Dillon E. , Csankovszki Gyorgyi
Published: February 2025

Dosage compensation (DC) inC. elegansutilizes a condensin complex that resembles mitotic condensins, but differs by one subunit, DPY-27. DPY-27 replaces SMC-4, one of the Structural Maintenance of Chromosome (SMC) proteins that is responsible for hydrolyzing ATP, required for condensation of DNA and other mitotic condensin functions. To understand if the ATPase function is required in DC, we first demonstrated that DPY-27 is capable of hydrolyzing ATPin vitro. Then, we used CRISPR/Cas9-mediated genome editing to generate an ATPase mutation indpy-27and demonstrated that this mutation results in a loss of DC. Specifically, we found that without ATPase function, DPY-27 containing condensin IDChas reduced capacity to bind DNA, condense the X chromosomes, and facilitate H4K20me1 enrichment on the X-chromosomes. Our results suggest that condensin IDC, like mitotic condensins, uses ATP hydrolysis to perform its functions, makingC. elegansDC a model for how activities attributed to mitotic condensins can be used to regulate gene expression.
Poly-L-Ornithine Coated Plant Scaffolds Support Motor Recovery in Rats after Traumatic Spinal Cord Injury
Authors: Couvrette Lauren J. , Walker Krystal L. A. , Bayat Arman , Modulevsky Daniel J. , Laliberté Alex , Cuerrier Charles M. , Leblanc-Latour Maxime , Hickey Ryan J. , Boudria Rose , Monty Ruthie , Obhi Ras-Jeevan K. , Shore Isabel , Galuta Ahmad , Tsai Eve C. , Bui Tuan , Pelling Andrew E.
Published: February 2025

Spinal cord injury (SCI) is a debilitating neurological condition with far-reaching consequences for patients, including loss of motor function and significant limitations to quality of life. Implantable biomaterials have emerged as a therapeutic strategy to modulate the SCI microenvironment and facilitate regeneration of axons. In this study, plant-derived cellulose scaffolds coated with poly-L-ornithine (PLO) are shown to support locomotor recovery and neural tissue repair in a rat model of spinal cord injury. Upon complete transection of the spinal cord, animals were implanted with a plant-derived scaffold coated in poly-L-ornithine, a positively charged amino acid chain that is known to promote neural stem cell differentiation into neurons and enhance myelin regeneration. Recovery of motor function was evaluated by the Basso, Beattie and Bresnahan (BBB) locomotor scale as well as the Karolinska Institutet Swim Assessment Tool (KSAT). Retrograde tracing of ascending sensory tracts revealed enhanced regeneration in animals that received the PLO-coated scaffold. Numerous β-III tubulin and neurofilament 200 positive fibers may indicate axonal sprouting within the cellulose scaffold and LFB staining highlights myelination around the PLO-coated scaffold. These results demonstrate the potential of plant-based biomaterials in a rat model of acute spinal cord injury and highlight their enhancement after PLO functionalization.
Knockoff procedure improves causal gene identifications in conditional transcriptome-wide association studies
Authors: Zhang Xiangyu , Wang Lijun , Zhao Jia , Zhao Hongyu
Published: February 2025

Transcriptome-wide association studies (TWASs) have been developed to nominate candidate genes associated with complex traits by integrating genome-wide association studies (GWASs) with expression quantitative trait loci (eQTL) data. However, most existing TWAS methods evaluate the marginal association between a single gene and the trait of interest without accounting for other genes within the same genomic region or the same gene from different tissues. Additionally, false-positive gene-trait pairs can arise due to correlations with the direct effects of genetic variants. In this study, we introduce TWASKnockoff, a new knockoff-based framework for detecting causal gene-tissue pairs using GWAS summary statistics and eQTL data. Unlike marginal testing in traditional TWAS methods, TWASKnockoff examines the conditional independence for each gene-trait pair, considering both correlations in cis-predicted expression across genes and correlations between gene expression levels and genetic variants. TWASKnockoff estimates the theoretical correlation matrix for all genetic elements (cis-predicted expression across genes and genotypes for genetic variants) by averaging estimations from parametric boot-strap samples and then performs knockoff-based inference to detect causal gene-trait pairs while controlling the false discovery rate (FDR). Through empirical simulations and an application to type 2 diabetes (T2D) data, we demonstrate that TWASKnockoff achieves superior FDR control and improves the average power in detecting causal gene-trait pairs at a fixed FDR level.
Unraveling diversity by isolating peptide sequences specific to distinct taxonomic groups
Authors: Bochalis Eleftherios , Patsakis Michail , Chantzi Nikol , Mouratidis Ioannis , Chartoumpekis Dionysios , Georgakopoulos-Soares Ilias
Published: February 2025

The identification of succinct, universal fingerprints that enable the characterization of individual taxonomies can reveal insights into trait development and can have widespread applications in pathogen diagnostics, human healthcare, ecology and the characterization of biomes. Here, we investigated the existence of peptide k-mer sequences that are exclusively present in a specific taxonomy and absent in every other taxonomic level, termed taxonomic quasi-primes. By analyzing proteomes across 24,073 species, we identified quasi-prime peptides specific to superkingdoms, kingdoms, and phyla, uncovering their taxonomic distributions and functional relevance. These peptides exhibit remarkable sequence uniqueness at six- and seven-amino- acid lengths, offering insights into evolutionary divergence and lineage-specific adaptations. Moreover, we show that human quasi-prime loci are more prone to harboring pathogenic variants, underscoring their functional significance. This study introduces taxonomic quasi-primes and offers insights into their contributions to proteomic diversity, evolutionary pathways, and functional adaptations across the tree of life, while emphasizing their potential impact on human health and disease.
The creation and validation of a fully animal component-free media for select adherent cell types
Authors: Mogilever Nicolette B. , Godin Pagé Marie-Hélène , Solola Anjolaoluwatikiitan , Pelling Andrew E.
Published: February 2025

Fetal Bovine Serum (FBS) is one of the most commonly used media supplement for the maintenance of mammalian cell types, yet the expensive costs, ethical concerns, and lot-to-lot variation have provoked a clear need for a serum that is standardized and derived from non-animal sources. Several serum-free formulations have been developed in the past, however they are often cell type specific, contain animal-derived components, and lack long-term culture validation. In this study, we developed a novel animal component-free (ACF) media and investigated its effectiveness on four commonly used mammalian cell lines via long-term (up to 90 days) morphological, transcriptomic, and proliferative analyses. Cells cultured in our ACF medium exhibited comparable cellular morphologies and equal or greater growth rates compared with cells cultured with FBS. Additionally, differentially expressed genes between the FBS-grown and ACF-grown groups were predominantly associated with functions linked to proliferation and cell attachment. The findings from this study indicate that this medium is a suitable replacement to FBS-containing medium for several common cell lines.
All-transretinoic acid and fluid transport in myopigenesis
Authors: Dvoriashyna Mariia , Bentley-Ford Melissa , Yu Jianshi , Chatterjee Saptarshi , Pardue Machelle T. , Kane Maureen A. , Repetto Rodolfo , Ethier C. Ross
Published: February 2025

Myopia, or near-sightedness, is rapidly growing in prevalence, with significant long-term implications for ocular health. There is thus great impetus to better understand molecular signaling pathways leading to myopia. We and others have reported that all-trans retinoic acid (atRA) is involved in myopigenic signaling, yet the understanding of how atRA is transported and exerts a myopigenic influence is poor. Here we measured the concentrations of atRA in the serum in wild-type C57BL/6 mice under control conditions and after atRA feeding, previously shown to induce myopia. We also developed a mathematical model that describes fluid fluxes and the advective-diffusive transport of atRA in choroid and sclera, including atRA synthesis in the choriocapillaris, atRA degradation by scleral cells, and binding of atRA to the carrier protein serum albumin. This model, developed for both mice and humans, showed that atRA produced in the choriocapillaris was able to permeate well into the sclera in both mice and humans at biologically-relevant concentrations, and that atRA feeding greatly increased tissue levels of atRA across both the choroid and sclera. We were also able to identify which parameters most influence atRA concentration in ocular tissues, guiding future experimental work. Our findings support atRA’s role in myopigenic signaling.
Multitask deep learning for the emulation and calibration of an agent-based malaria transmission model
Authors: Mondal Agastya , Anirudh Rushil , Selvaraj Prashanth
Published: February 2025

Agent-based models of malaria transmission are useful tools for understanding disease dynamics and planning interventions, but they can be computationally intensive to calibrate. We present a multitask deep learning approach for emulating and calibrating a complex agent-based model of malaria transmission. Our neural network emulator was trained on a large suite of simulations from the EMOD malaria model, an agent-based model of malaria transmission dynamics, capturing relationships between immunological parameters and epidemiological outcomes such as age-stratified incidence and prevalence across eight sub-Saharan African study sites. We then use the trained emulator in conjunction with parameter estimation techniques to calibrate the underlying model to reference data. Taken together, this analysis shows the potential of machine learning-guided emulator design for complex scientific processes and their comparison to field data.

Author summary

Mathematical models can help understand and design interventions for infectious diseases such as malaria, but they can be complex and time-consuming to work with. In this study, we developed a machine learning approach to create a fast and accurate emulator for a detailed malaria transmission model. Our emulator can quickly predict various disease outcomes based on different immune system parameters. We trained it using a large set of simulations created using the EMOD malaria model and tested it against real-world data from multiple African countries. The emulator not only matches the original model’s predictions closely, but can also be used to efficiently find the best parameter values to match field observations. We hope that this work can serve as a demonstration of machine learning tools to link complex models of disease transmission to field data.
Sequence similarity estimation by random subsequence sketching
Authors: Chen Ke , Pattar Vinamratha , Shao Mingfu
Published: February 2025

Sequence similarity estimation is essential for many bioinformatics tasks, including functional annotation, phylogenetic analysis, and overlap graph construction. Alignment-free methods aim to solve large-scale sequence similarity estimation by mapping sequences to more easily comparable features that can approximate edit distances efficiently. Substrings or kmers, as the dominant choice of features, face an unavoidable compromise between sensitivity and specificity when selecting the properk-value. Recently, subsequence-based features have shown improved performance, but they are computationally demanding, and determining the ideal subsequence length remains an intricate art. In this work, we introduce SubseqSketch, a novel alignment-free scheme that maps a sequence to an integer vector, where the entries correspond to dynamic, rather than fixed, lengths of random subsequences. The cosine similarity between these vectors exhibits a strong correlation with the edit similarity between the original sequences. Through experiments on benchmark datasets, we demonstrate that SubseqSketch is both efficient and effective across various alignment-free tasks, including nearest neighbor search and phylogenetic clustering. A C++ implementation of SubseqSketch is openly available athttps://github.com/Shao-Group/SubseqSketch.
SortingF. graminearumcore effector candidates shows multiple fungal proteins that target the wheat cell nucleus during Fusarium Head Blight
Authors: Ayilalath Shimlal , Faurie Lilian , Vanrobays Emmanuel , Rocher Florian , Loizeau Loriane , Philippe Géraldine , Javel Marie , Bosio Mickaël , Sallaud Christophe , Tatout Christophe , Bonhomme Ludovic
Published: February 2025

Effectors are small molecules secreted by microbial pathogens that disrupt host basal functioning and responses during infection by targeting various plant susceptibility factors. This study reports a candidate selection approach for identifying novel, potential plant nuclear localized effectors fromFusarium graminearumsecretory proteins. From a dataset of core secretory proteins conserved across severalFusariumstrains, candidates were selected based on predicted nuclear localization, structural characteristics, and expression profiles during infection. Transient expression inNicotiana benthamianaconfirmed accumulation in the plant nucleus, that were further confirmed in wheat protoplasts. One of these proteins was selected for yeast two-hybrid (Y2H) screening to identify wheat protein targets, using aFusarium-infected wheat spike cDNA library specifically generated for this study. The screening identified a high confident interaction with a nuclear-localized wheat beta-amylase 2. The structural modeling of the protein complex between beta-amylase 2 and the putative effector was used to predict interacting amino acid residues and informed a deletion analysis to disrupt the interaction. This research identifies aF. graminearumsecretory core protein that interacts with a conserved wheat beta-amylase 2, showcasing a method to select pathogenicity factors conserved across multiple pathogens and host plants, with implications for developing broad-spectrum resistance strategies.

Highlight

This study proposes a method based onin silicoandin vivoscreens to identify interacting pairs between core pathogenicity effectors localized in the nucleus and susceptibility factors in plants.
Beyond RNA Structure Alone: Complex-Aware Feature Fusion for Tertiary Structure-based RNA Design
Authors: Zhang Zixun , Zheng Jiayou , Zhou Yuzhe , Wang Sheng , Cui Shuguang , Li Zhen
Published: February 2025

Tertiary structure-based RNA design plays a crucial role in synthetic biology and therapeutics. While existing methods have explored structure-to-sequence mappings, they focus solely on RNA structures and overlook the role of complex-level information, which is crucial for effective RNA design. To address this limitation, we proposettheComplex-Aware tertiary structure-basedRNADesign model,CARD, that integrates complex-level information to enhance tertiary structure-based RNA sequence design. To be specific, our method incorporates protein features extracted by protein language model (e.g., ESM-2), enabling the design model to generate more accurate and complex relevant sequences. Considering the biological complexity of protein-RNA interactions, we introduce a distance-aware filtering for local features from protein representation. Furthermore, we design a high-affinity design framework that combines our CARD with an affinity evaluation model. In this framework, candidate RNA sequences are generated and rigorously screened based on affinity and structural alignment to produce high-affinity RNA sequences. Extensive experiments demonstrate the effectiveness of our method with an improvement of5.6%compared with base model without our complex-aware feature integration. A concrete case study for 2LBS further validates the superiority of our CARD.
Deep origins and distinct adaptations indicated for a glacial relict seal
Authors: Löytynoja Ari , Pohjoismäki Jaakko , Valtonen Mia , Laakkonen Juha , Morita Wataru , Kunnasranta Mervi , Väinölä Risto , Olsen Morten Tange , Auvinen Petri , Jernvall Jukka
Published: February 2025

Isolated populations of postglacial relicts are known from many regions and are typically found on mountains for terrestrial species and in lakes for aquatic species. Among the few aquatic mammalian relicts, the Saimaa ringed seal (Pusa hispida saimensis) has been land-locked in Lake Saimaa, Finland, for the last 10,000 years. Saimaa ringed seals show genetic, behavioral, and morphological differences to the other ringed seal subspecies, but the extent these differences stem from the end of the last glacial period remains unclear. Here, we demonstrate with comprehensive sampling and state-of-the-art genomic methods that the Saimaa ringed seals are much older than the lake they inhabit, having formed a separate evolutionary branch for at least 60,000 years ago. This deep evolutionary origin of the Saimaa ringed seals is further underscored by our ecomorphological analyses revealing adaptively distinct features in their dentition and tongue. Overall, glacial relicts, many threatened by extinction, may harbor a richer selection of evolutionary history than might be expected from their recent isolation history alone.
Infection signatures of multipleNucleocytoviricotavirus lineages in the brown algaeUndaria pinnatifidarevealed by population-wide genome analysis
Authors: Ban Hiroki
Published: February 2025

Undaria pinnatifidais a large brown algae native to the northwest Pacific. It has been introduced to numerous countries and is listed among the world’s 100 worst invasive species. However, it is also edible and produces various bioactive compounds, making it commercially important. Despite its ecological and economic value, the viruses that infectU. pinnatifidaremain unknown. In this study, a population-wide genome analysis was performed to investigate viral infection signatures inU. pinnatifida. A nearly complete 551-Kb giant endogenous viral element of aNucleocytoviricotavirus was identified on a pseudochromosome in the Korean strain genome Upin_Kr2015. This viral region contained viral hallmark genes and auxiliary metabolic genes, including kinases and GDP-mannose dehydrogenase. Additionally, we detected viral hallmark genes in all 43 whole-genome assemblies analyzed, with origins tracing to the ordersPandoravirales,Algavirales, orImitevirales. Our findings provide strong evidence of frequentU. pinnatifidainfections by multipleNucleocytoviricotaviruses.
Targeting FGFR4 Abrogates HNF1A-driven Metastasis in Pancreatic Ductal Adenocarcinoma
Authors: Crawford Katherine J. , Humphrey Kennedy S. , Cortes Eduardo , Wang Jianxin , Feigin Michael E. , Witkiewicz Agnieszka K. , Knudsen Erik S. , Abel Ethan V.
Published: February 2025

Purpose

We previously identified an oncogenic role for the transcription factor HNF1A in pancreatic ductal adenocarcinoma (PDAC). However, the role of HNF1A in the metastatic progression of PDAC remains unknown and targeting modalities for HNF1A -dependent phenotypes have yet to be identified.

Experimental Design

Transwell chambers were used to assess the effects of HNF1A and FGFR4 modulation on the migration and invasion of ATCC and patient-derived PDAC cellsin vitro. An intrasplenic injection xenograft model was used to evaluate the impact of HNF1A knockdown and overexpression on metastatic tumor burden. Single-cell RNA sequencing, tissue microarray (TMA) data, and UMAP spatial profiling were used to identify FGFR4 as an HNF1A target gene upregulated in metastatic cells. RNAi and two FGFR4 inhibiting modalities (H3B-6527 and U3- 1784) were utilized to demonstrate the efficacy of FGFR4 inhibiting agents at reducing HNF1A- driven metastasis.

Results

Knockdown of HNF1A significantly decreases and HNF1A overexpression significantly increases PDAC cell migration and invasion.In vivostudies show that HNF1A knockdown significantly abrogates metastasis, while overexpression significantly promotes metastasis. Single-cell RNAseq shows that FGFR4 is upregulated in metastatic PDAC cells and staining for HNF1A and FGFR4 in a PDAC TMA reveals significant correlation between HNF1A and FGFR4 in PDAC patients. Further, knockdown and inhibition of FGFR4 significantly decreases HNF1A- mediated cell migration and invasion, and blocks HNF1A-driven metastasisin vivo.

Conclusions

These findings demonstrate that HNF1A drives PDAC metastasis via upregulation of FGFR4, and FGFR4 inhibition is a potential mechanism to target metastasis in PDAC patients.

Translational Relevance

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, made even more devastating when metastases overwhelm major organs. The vast majority of PDAC patients either present with metastases or will relapse with recurrent metastatic PDAC after primary tumor resection. Unfortunately, toxic and largely ineffective chemotherapies are currently the only approved treatment options for these patients and therefore there exists a critical and unmet clinical need for targeted therapies against pro-metastatic pathways in PDAC. In the current study, we identify HNF1A as an oncogenic transcription factor that drives metastasis in PDAC, and it does so through upregulation of the receptor tyrosine kinase FGFR4. Importantly, FGFR4 is a targetable vulnerability and treatment with an FGFR4 blocking antibody reduces HNF1A-driven metastasis. These findings suggest that FGFR4 inhibitors could be an efficacious treatment for PDAC patients for the prevention or delay of metastatic tumor development.
An oomycete effector that induces shade avoidance like growth and suppresses plant defenses targets the AUX/IAA protein IAA11
Authors: Bogino Maria Florencia , Lapegna Senz Juan Marcos , Tamagnone Nicolás , Kourdova Lucille Tihomirova , Romanowski Andrés , Wirthmueller Lennart , Fabro Georgina
Published: February 2025

Filamentous pathogens, such as oomycetes, employ multiple strategies to suppress plant immunity, one of which involves manipulating phytohormone signaling pathways. The effector HaRxL106 from Hyaloperonospora arabidopsidis (Hpa), known to induce shade avoidance syndrome (SAS)-like growth, has previously been shown to interact with brassinosteroid signaling components. Here, we investigate the role of HaRxL106 in altering auxin signaling, revealing that HaRxL106 targets the AUX/IAA protein IAA11, a key negative regulator of auxin responses. Our data suggest that HaRxL106 impedes the repressive function of IAA11, enhancing auxin signaling and promoting SAS, which concurrently suppresses plant immune responses. These findings provide insights into how pathogen effectors manipulate plant growth and immunity to facilitate infection.
Asymmetric subspecies-selection of an NLR-TF immune module and reconstruction of broad-spectrum disease resistance in rice
Authors: Lin Hui , Chen Fudan , Cheng Guanyun , Yan Bingxiao , Yuan Meng , Qiu Jie , Chen Ying , Wang Yijie , Cui Kaixuan , Gong Xiangyu , Liu Shasha , Liu Jiyun , Wang Jianjun , Li Rongbai , Mao Bizeng , Xu Jianlong , Jeon Jong-Seong , Huang Xuehui , Han Bin , Deng Yiwen , Chen Gongyou , He Zuhua
Published: February 2025

Artificial selection has greatly shaped crop agronomic traits; however, the mechanistic basis of immunity selection has remained elusive. This study identifies a new rice NLR XA48 and its downstream transcription factor OsVOZ1, which confer bacterial blight resistance. XA48 perceives an ancient pathogen effector, XopG, to activates effector-triggered immunity (ETI). The XA48-OsVOZ1 module has undergone subspecies-specific selection.Xa48is retained inindicabut functionally lost injaponicarice. OsVOZ1 has also diverged into two haplotypes,indicakept both OsVOZ1A/Salleles that match XA48; whilejaponicaonly inherited OsVOZ1Athat greatly decreases yield whenXa48is reintroduced intojaponica, mechanistically explaining theXa48loss injaponica. We resurrected wild rice broad-spectrum resistance by stacking XA48-mediated ETI with XA21-mediated pattern-triggered immunity (PTI). Thus, our study reveals that the asymmetric selection of an NLR-TF module shapes both disease resistance and reproduction, and provides a paradigm for breeding crops by harnessing the immunity of wild relatives.
Wild and farmedSaccharina latissimain Europe: genetic insights for sustainable cultivation, traceability and environmental challenges
Authors: Jaugeon Lucie , Destombe Christophe , Ruggeri Paolo , Mauger Stéphane , Coudret Jérôme , Cock J. Mark , Potin Philippe , Valero Myriam
Published: February 2025

Kelp cultivation is expanding rapidly worldwide, although the aquaculture ofSaccharina latissima(sugar kelp) in Europe remains in its early stages. However, major concerns have emerged about the potential impact of selected cultivars of the species on native populations ofS. latissimawhich are already vulnerable to stressors including climate change.

To address these concerns and support sustainable cultivation, it is essential to characterise genetic diversity and structure of wild kelp populations to monitor potential farm-to-wild gene flow. In this study we used 21 microsatellite loci to characterise the genetic structure of 24 natural and 3 farmed populations ofS. latissimaalong European coasts. Results confirmed strong genetic differentiation between the northern and southern coasts, refining the boundaries between these two clusters compared to previous studies. Within each cluster, a clear genetic substructure was detected, with population differentiation being far more pronounced in the southern cluster.

Cultivated sporophytes exhibited pedigrees that were all traced back to the local parent populations. Bayesian model-based structure analysis, discriminant analysis of principal components and assignment tests revealed no significant genetic differentiation between the farms and their wild populations. This indicates that farmed populations and neighbouring populations share the same gene pool, reflecting current cultivation practices. These findings contribute to understanding risks of gene flow between wild and farmed populations and demonstrate that strain traceability is feasible. Additionally, the study highlights the challenge European seaweed farmers face in securing reliable seedling stock, especially in the context of global change.
A combined computational and experimental approach to successfully predict the behavior of metastatic tumor-associated macrophages in human breast cancer
Authors: Bekkar Amel , Pabois Angélique , Crespo Isaac , Turrini Riccardo , Xenarios Ioannis , Doucey Marie-Agnès
Published: February 2025

We identified in human breast cancer a scarce population of Tumor-Associated Monocytes (TAMs) endowed with a pro-metastatic activity and associated with reduced distant-metastasis free survival of patients. We developed a novel framework combining computational and experimental methodologies to dampen TAM pro-metastatic activity. Multi-modal experimental data from TAMs exposed in vitro to a series of perturbations were collected to build a Boolean dynamical network of TAMs. This framework successfully identified the biological pathways underlying TAM pro-metastatic activity and predicted potent pharmacological interventions that inhibited the pro-metastatic activity of TAMs isolated from patient tumors. This study showcases the power of integrating computational predictions with experimental validation in identifying new therapeutic avenues that can be extended to other cancer types.
Dynamic Predictive Spatial Encoding of Motor Intentions In Area V6A of the Posterior Parietal Cortex
Authors: Buonfiglio Antonio Roberto , Diomedi Stefano , Filippini Matteo , Fattori Patrizia , Stoianov Ivilin Peev
Published: February 2025

To compute motor plans or intentions, the nervous system must translate tar-get locations into body-centered coordinates. Visual stimuli, however, are sensed in retinotopic coordinates, which shift with eye movements. Furthermore, sen-sorimotor delays necessitate predictive processing. How does the brain compute timely gaze-invariant target locations? The dorsal visual pathway encodes spa-tial intentions, yet the underlying dynamic mechanisms remain elusive. Using multilevel analysis, we characterized intention coding in area V6A of the Pos-terior Parietal Cortex during delayed reaching tasks under diverse gaze-target conditions. We revealed a consistent population-level intention coding in V6A as eye positions changed. Next, we identified differential single-cell encoding of gaze and reaching targets in retinotopic, gaze-posture, and body-centered coordinates and elucidated the dynamical spatial normalization. Finally, we demonstrated context-dependent predictive spatial encoding in V6A, advancing our understand-ing of the temporal evolution of predictive visuomotor transformations during motor planning.
Parasite-mediated inbreeding depression in wild red deer
Authors: Hasik Adam Z , Hewett Anna , Maris Katie , Morris Sean , Morris Ali , Albery Gregory F , Pemberton Josephine M.
Published: February 2025

Inbreeding depression is the reduction in fitness of inbred individuals relative to their more outbred counterparts. Parasitism also reduces fitness and is a route by which inbreeding depression may operate, yet the complete pathway from inbreeding to parasitism to fitness has almost never been documented in the wild. Using high-quality, individual-level data on fitness in juveniles and adult females, longitudinal infection data for three gastrointestinal helminth parasites, and genomic inbreeding coefficients we test for parasite-mediated inbreeding depression in a wild ungulate population (red deer, Cervus elaphus). We found evidence for parasite-mediated inbreeding depression via strongyle nematodes in juvenile survival, independent of direct adverse effects of inbreeding on survival and indirect effects of inbreeding on survival via birth weight. Inbreeding also reduced fitness in reproductive adults by reducing overwinter survival. Our study reveals three independent pathways by which inbreeding depresses fitness and highlights the rarely-studied route of parasitism.
A Sacrificial 3D Printed Vessel-on-Chip Demonstrates a Versatile Approach to Model Connective Tissue Pathology
Authors: Jäger Jonas , Berger Phil , Morrison Andrew I. , Erfurth Hendrik , Thon Maria , Dehne Eva-Maria , Gibbs Susan , Koning Jasper J.
Published: February 2025

Forin vitroorgan models, perfused vasculature is crucial to overcome nutrient diffusion limits and to generate immunocompetent models by allowing trans-endothelial migration of immune cells in and out of the tissue. However, vasculature is often disregarded due to its complexity to generate and the necessity to integrate flow. The aim here was to overcome these limitations by combining 3D printing and multi-organ-chip technology to generate a vascularized, fibroblast-populated connective tissue matrix on-chip. A 3D printed, sacrificial, water-dissolvable structure was incorporated into a multi-organ-chip during its fabrication and hollow channels within a collagen/fibrin hydrogel were generated. Subsequently, channels were populated with endothelial cells and varying hydrogel concentrations (Fhigh/Chigh) used to mimic healthy and diseased connective tissue. The vessels were perfused and stable metabolic/viability conditions (lactate dehydrogenase, glucose, lactate) acquired after 3 days for at least 7 days. Angiogenic sprouting and secretion of angiogenic cytokines were increased in Fhighhydrogels. Perfusion with monocytes revealed differentiation into macrophages and migration across the endothelium into the tissue. In conclusion, this versatile, easy method to pattern hydrogels in a multi-organ-chip can serve as the basis to build the next generation of vascularized, immunocompetent human organ models, and opens new possibilities to study health and disease.
Effects of Interleukin-6 dysregulation in a mouse model of Alzheimer’s disease: unraveling the complexity beyond amyloidosis
Authors: Canal Carla , Aguilar Kevin , Comes Gemma , Sanchis Paula , Molinero Amalia , Giralt Mercedes , Hidalgo Juan
Published: February 2025

1.

Interleukin-6 dysregulation has been implicated in the pathological progression of Alzheimer’s disease (AD), a leading cause of dementia in the ageing population. Here we show that chronic neuroinflammation elicited by transgenic expression of IL-6 and systemic IL-6 deficiency influences the phenotype of the Tg2576 mouse model of AD, modulating mortality, body weight, behavioral and cognitive traits, amyloidosis, and neuroinflammation. While the conventional understanding of AD pathophysiology emphasizes the central role of Aβ peptides and amyloid plaques in the development and progression the disease, the absence of amyloidosis in the brain in a specific subset of Tg2576 mice challenges this notion. This suggests that several Tg2576-related traits may manifest independently of Aβ, pointing to a potential contribution of alternative APP-related factors or pathways to the phenotypic alterations observed in Tg2576 mice. Together, our findings underscore the complexity of AD pathogenesis and emphasize the multifaceted nature of IL-6 in both physiological and neurodegenerative processes, particularly in the context of AD.
SAMCell: Generalized Label-Free Biological Cell Segmentation with Segment Anything
Authors: VandeLoo Alexandra D. , Malta Nathan J. , Aponte Emilio , van Zyl Caitlin , Xu Danfei , Forest Craig R.
Published: February 2025

Background

When analyzing cells in culture, assessing cell morphology (shape), confluency (density), and growth patterns are necessary for understanding cell health. These parameters are generally obtained by a skilled biologist inspecting light microscope images, but this can become very laborious for high throughput applications. One way to speed up this process is by automating cell segmentation. Cell segmentation is the task of drawing a separate boundary around each individual cell in a microscope image. This task is made difficult by vague cell boundaries and the transparent nature of cells. Many techniques for automatic cell segmentation exist, but these methods often require annotated datasets, model retraining, and associated technical expertise.

Results

We present SAMCell, a modified version of Meta’s Segment Anything Model (SAM) trained on an existing large-scale dataset of microscopy images containing varying cell types and confluency. We find that our approach works on a wide range of microscopy images, including cell types not seen in training and on images taken by a different microscope. We also present a user-friendly UI that reduces the technical expertise needed to use this automated microscopy technique.

Conclusions

Using SAMCell, biologists can quickly and automatically obtain cell segmentation results of higher quality than previous methods. Further, these results can be obtained through our custom GUI without expertise in Machine Learning, thus decreasing the human labor required in cell culturing.