bluuebunny/crossref_metadata_2025 huggingface dataset:
Lizards in energy-saving mode: Urban individuals are smaller and have lower metabolic rates
Authors: Rimbach Rebecca , Maraci Oncu , Maune Avery L. , Damas-Moreira Isabel
Published: February 2025

Human-induced rapid environmental change is intensifying globally. Urbanization, a major form of human-induced rapid environmental change, alters ecosystems and exposes wildlife to urban stressors, including altered ambient temperatures and resource shifts. These alterations can impose selective pressures on wildlife, influencing behavior, physiology, and morphology. Alterations in resource availability and quality, and ambient temperature may be especially important for ectotherms, which depend on environmental conditions for regulating body temperature and activity. To date, little research has examined the physiological changes of ectotherms that are associated with urban life. In this study, we measured standard metabolic rate (SMR; N = 38) and recorded body mass and size in common wall lizards (Podarcis muralis) from an urban (N = 123) and a semi-natural habitat (N = 125) in Croatia. Our results show that urban lizards exhibit a lower SMR, reduced body mass, and shorter snout-vent length than their semi-natural counterparts. Despite these differences, body condition, assessed via the scaled mass index, did not vary between the two habitat types, potentially reflecting adaptive responses to urbanization-related environmental pressures. These findings suggest adaptive strategies of reptiles in urban environments and highlight the importance of studying both physiological and morphological traits to better understand the effects of urbanization on wildlife.
Inverse Agonism of the FFA4 free fatty acid receptor controls both adipogenesis and mature adipocyte function
Authors: Alshammari WS , Duncan EM , Vita L , Kenawy M , Dibnah B , Wabitsch M , Gould G , Hudson BD
Published: February 2025

Adipocyte disfunction is an important component of many metabolic disorders and there is a need for pharmacological approaches that can restore normal adipocyte function. The FFA4 receptor is a G protein coupled receptor (GPCR), activated by long chain free fatty acids (FFAs), that controls adipocyte function. Importantly, adipocytes produce FFAs, which may directly activate FFA4 and there is a need to better understand how FFAs produced by adipocytes interact with FFA4 signalling. In this study we have employed human and mouse adipocyte cell models to determine how pharmacological agonism or antagonism of FFA4 affects adipogenesis, lipolysis and glucose uptake. We show that a commonly used FFA4 antagonist, AH7614, is an inverse agonist and that treating adipocytes with this compound suppressed adipogenesis, inhibits glucose uptake and enhances isoprenaline stimulated lipolysis. In contrast, treatment with a synthetic FFA4 agonist, TUG-891, has only modest effects on adipogenesis and lipolysis, while showing no effect on glucose uptake. To explore the mechanism for why AH7614 but not TUG-891 affects adipocyte function, we demonstrate that during adipogenic differentiation sufficient FFAs are released into the culture medium to activate FFA4, suggesting AH7614 inhibits an autocrine feedback loop to suppress adipogenesis. In contrast, during lipolysis experiments, insufficient FFAs were released to activate the receptor, suggesting that AH7614 must enhance lipolysis by either inhibiting ligand independent FFA4 signalling, or FFA signalling that does not require the FFAs to be released from the cell. This study will help establish how FFA4 targeting therapeutics could be used to treat adipocyte dysfunction.
Lifetime changes in Body map based on music prediction
Authors: Tanaka Masaki , Daikoku Tatsuya
Published: February 2025

This study aims to investigate the relationship between music, which is said to promote well-being, and emotions as well as bodily sensations across the lifespan. Using eight chord progressions based on predictive models, we conducted online experiments with 784 participants aged 10 to 80, evaluating bodily sensation mapping and emotional responses. The results revealed that bodily sensations peaked in the 20s to 30s and subsequently declined with age, particularly for chords with low prediction error and uncertainty. On the other hand, arousal levels increased with age and showed a strong correlation with predictable musical structures. These findings suggest that bottom-up bodily responses diminish with ageing, while supporting the relationship between top-down processing shaped by accumulated experience and the predictability of music, as indicated by previous research. This study enhances the development of music-based interventions that improve well-being across generations, considering the unique physical and emotional characteristics of each age group.
A Mathematical Model for Chemo-mechanically Induced Collective Cell Motility on Planar Elastic Substrates
Authors: Ahmed Riham K. , Abdalrahman Tamer , Davies Neil H. , Vermolen Fred , Franz Thomas
Published: February 2025

Cells interact with mechanical and chemical environmental cues, such as mechanical cues from other cells and chemical signals from growth factors. The current study aims to develop a mathematical model for combined chemically and mechanically induced collective cell motility on planar substrates. In this model, an extension of a previous model simulates cell motility induced by strain energy density gradients in the planar substrate originating from cellular traction forces is presented to capture the effect of a growth factor gradient and describe chemo-mechanically induced deterministic collective cell motility on planar elastic substrates. Green’s function and Duhamel’s principle are used to solve the diffusion equation that describes the distribution of a growth factor and to represent chemo-mechanically induced deterministic collective cell motility on planar elastic substrates. The migratory displacement and velocity of a single cell towards the growth factor source on the elastic substrate are demonstrated for varying growth factor production and diffusion rates. Chemically induced motility of 25 cells towards the growth factor source is predicted for different growth factor production and diffusion rates. Chemo-mechanical cues with varying growth factor production and diffusion rates are explored for the motility of four cells and one motile cell in the presence of one stationary cell. The developed model describes the chemo-mechanically induced motility of individual cells on planar substrates. The model provides valuable information forin vivoorin vitrodue to its suitability for extension to other chemical source shapes, mobilized sources, many sources, and soluble concentration gradients.
scBSP: A fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data
Authors: Li Jinpu , Raina Mauminah , Wang Yiqing , Xu Chunhui , Su Li , Guo Qi , Ferreira Ricardo Melo , Eadon Michael T , Ma Qin , Wang Juexin , Xu Dong
Published: February 2025

Emerging spatial omics technologies empower comprehensive exploration of biological systems from multi-omics perspectives in their native tissue location in two and three- dimensional space. However, sparse sequencing capacity and growing spatial resolution in spatial omics present significant computational challenges in identifying biologically meaningful molecules that exhibit variable spatial distributions across different omics. We introduce scBSP, an open-source, versatile, and user-friendly package for identifying spatially variable features in high-resolution spatial omics data. scBSP leverages sparse matrix operation to significantly increase computational efficiency in both computational time and memory usage. In diverse spatial sequencing data and simulations, scBSP consistently and rapidly identifies spatially variable genes and spatially variable peaks across various sequencing techniques and spatial resolutions, handling two- and three-dimensional data with up to millions of cells. It can process high-definition spatial transcriptomics data for 19,950 genes across 181,367 spots within 10 seconds on a typical desktop computer, making it the fastest tool available for handling such high-resolution, sparse spatial omics data while maintaining high accuracy. In a case study of kidney disease using 10x Xenium data, scBSP identified spatially variable genes representative of critical pathological mechanisms associated with histology.
VAMP8 Deficiency Attenuates AngII-Induced Abdominal Aortic Aneurysm Formation via Platelet Reprogramming and Enhanced ECM Stability
Authors: Mohammadmoradi Shayan , Driehaus Elizabeth R. , Alfar Hammodah R. , Joshi Smita , Whiteheart Sidney W.
Published: February 2025

BACKGROUND

As vascular sentries, platelets, and their ability to release a host of bioactive molecules, are critical for vascular homeostasis as well as hemostasis. Despite data linking platelet activation to abdominal aortic aneurysms (AAA) and rupture, the underlying mechanisms remain poorly understood. This study addresses the hypothesis that VAMP8, the primary v-SNARE controlling platelet exocytosis, contributes to AAA formation.

METHODS AND RESULTS

In an AngII-infused hypercholesterolemic mouse model, we observed significant platelet consumption, indicated by decreased platelet counts at both acute (5-day) and chronic (28-day) time points. Platelets accumulated at sites of elastin degradation and within false lumens of the abdominal aorta after 28 days of AngII infusion. Bulk RNA sequencing analysis of washed platelets and their releasates after 5 days of AngII infusion revealed significant transcriptomic changes, suggesting rapid reprogramming of platelet function. Parallel RNA-seq analysis of suprarenal aortic tissue highlighted changes in genes associated with extracellular matrix (ECM) organization, inflammation, and platelet signaling, linking platelets to vascular remodeling suggesting a “platelet-aorta axis”. Laser speckle imaging in a FeCl₃ injury model confirmed that VAMP8 deficiency impaired platelet function, resulting in delayed thrombosis.In vivoexperiments demonstrated that VAMP8⁻/⁻ mice were protected against AngII-induced AAA and aortic rupture. Aortic diameter analysis further revealed that VAMP8 deficiency significantly attenuated AngII-driven aortic pathology. RNA-seq analysis of platelets and aortic tissue suggests that loss of VAMP8 affects expression of genes controlling ECM degradation and aortic wall stability consistent with the protective effect of VAMP8 loss on AAA.

CONCLUSION

Short-term AngII infusion appears to reprogram the platelet transcriptome, which may affect the aorta and contribute to AAA formation. Controlling cargo release from platelets via VAMP8 deficiency results in profound attenuation of aortic aneurysms. This introduces a novel paradigm for understanding the impact of reprogrammed platelet cargo secretion and function in aortopathies.

Graphical Abstract

Highlights

Platelet transcriptome is altered at early aneurysmal stage.

VAMP8 deficiency attenuates aortic aneurysms, potentially via enhanced ECM stability.

VAMP8 deficiency significantly alters various genes contributing to aortic wall structure and stability in both platelets and suprarenal aortic tissue.
Free-Form Microfluidic Microneedle Array Patches
Authors: Coates Ian A. , Driskill Madison M. , Rajesh Netra U. , Lipkowitz Gabriel , Ilyin Dan , Xu Yue , Dulay Maria T. , Jacobson Gunilla B. , Perry Jillian L. , Tian Shaomin , DeSimone Joseph M.
Published: February 2025

Personalized biomedical devices, such as microneedle array patches (MAPs), offer a promising transdermal drug delivery technology, providing a safe, painless, and self- administered alternative to traditional hypodermic injections. Despite their potential for precise therapeutic release, MAP adoption has been limited by challenges in payload capacity, treatment versatility, and manufacturing scalability. To address these issues, we integrated microfluidic channel designs with MAP technology, enhancing its functionality for delivering a range of payloads, from liquid therapeutics to solid-state cargos, at tunable volumes. Using injection continuous liquid interface production (iCLIP), a novel additive manufacturing approach, we fabricated high-resolution microfluidic MAPs with complex designs. Inspired by the stingers and fangs of various venomous animals, we developed a biomimetic microneedle design that prevents clogging, enhances mechanical strength, and eliminates needle leakage, thereby improving therapeutic delivery efficiency. Our technology reliably delivers multiple distinct payloads, enables combinational mixing, and enables point-of-care reconstitution of solid-state payloads.

Teaser

Leveraging biomimetic design and advanced 3D printing, we developed high-resolution microfluidic microneedle array patches (MAPs) that overcome payload and scalability challenges, offering a versatile and efficient platform for precise transdermal drug delivery.
A typology of Australian terrestrial bird communities
Authors: Maron Martine , Indraswari Karlina , Mills-Anderson Jonathan , Melton Courtney B. , Mayfield Helen J. , Possingham Hugh , Radford James , Reside April E. , Bennett Andrew , Burbidge Allan , Clarke Michael , Clarke Rohan H. , Davis Robert , Eyre Teresa , Freeman Amanda , Gibson Michelle , Hansen Birgita , Haslem Angie , Humphrey Jacinta , Jackett Nigel , Palmer Bryony , Kutt Alex , Leseberg Nicholas P. , Loyn Richard , Maisey Alex , Maurer Golo , McDonald Paul , Mihailou Helenna , Noske Richard , Rainsford Fred , Reid Julian , Robinson Doug , Selwood Katherine , Simmonds Jeremy S. , Spindler Rebecca , Teixeira Daniella , Tulloch Ayesha , Vanderduys Eric , Verdon Simon , Watson David , Watson James , Fraser Hannah
Published: February 2025

Aim

Increasing interest in holistic measurement of the response of fauna communities to interventions requires suitable community condition metrics. However, the development of such metrics is hindered by the absence of broad-scale typologies at suitable spatial and ecological resolutions. We aimed to derive a preliminary typology of terrestrial bird communities for Australia, based on bird co-occurrence data, and describe and map the likely distribution of each community type across the continent.

Location

Mainland Australia, continental islands

Time period

1973-2022

Major taxa studied

Aves

Methods

We used fine-scale co-occurrence data from standard 2-ha surveys in BirdLife Australia’s citizen-science database. After filtering to reduce bias, we used hierarchical clustering followed by iterative consultation with experts to identify reliably distinct and recognisable terrestrial bird communities across Australia. We used Maxent to model the likely distributions of each community, and developed community descriptions based on each community’s composition and distribution.

Results

The resultant typology included 29 reliably distinct and recognisable bird communities with major clusters corresponding with seven broad geographical regions. The distributions of bird communities did not correspond tightly to the boundaries of major vegetation groups, with most communities occurring across multiple vegetation types.

Main Conclusions

Our preliminary typology of bird communities provides a standard classification at a continental scale. It newly defines distinct bird communities as entities for which condition benchmarks can be established to allow assessment of their conservation status and monitoring of change over time.

Refinement will enable cryptic communities in areas with sparse data to be identified. The method could be translated to other regions where adequate coverage of data in the form of standardised surveys of fauna are available. Vast biodiversity datasets delivered through citizen science programs provide the opportunity to develop such typologies for fauna communities, as a precursor to developing targeted and informative community condition metrics.
Specimen-tailored “lived” climate reveals precipitation onset and amount best predict specimen phenology, but only weakly predict specimen reproductive success across a clade
Authors: Bontrager Megan G. , Worthy Samantha J. , Leventhal Laura C. , Maloof Julin A. , Gremer Jennifer R. , Schmitt Johanna , Strauss Sharon Y.
Published: February 2025

Herbarium specimens are broadly distributed in space and time, enabling investigation of impacts of climate on phenology and persistence Many studies have revealed climate-associated phenological shifts; we ask which of temperature, precipitation, or the timing of precipitation onset best explain specimen phenological stage, and whether the same variables also explain specimen reproduction, a measure closely aligned with fitness.

We calculated specimen-specific climate from estimated specimen germination date until average collection dates for 14 annual species ofStreptanthusandCaulanthus(Brassicaceae). We also test whether relationships of phenology and reproduction with climate variables are evolutionarily constrained.

Precipitation amount and onset date predicted specimen phenology, but much less so, specimen reproductive success. Earlier rainfall onset was associated with more phenologically advanced specimens, a relationship that showed evolutionary conservatism; however, such advancement had little effect on specimen reproduction. This lack of correlation may arise from processes like phenological shifts that buffer fitness impacts of climate, interactions with other community members also responding to climate, or challenges in estimating total reproduction from herbarium specimens.

We make suggestions for collection protocols that could improve the usefulness of herbarium data to understand climate impacts on reproduction, a better predictor than phenology of future population viability.
Actions of the Anti-Seizure Drug Carbamazepine in the Thalamic Reticular Nucleus: Potential Mechanism of Aggravating Absence Seizures
Authors: Jang Sung-Soo , Agranonik Nicole , Huguenard John R.
Published: February 2025

Carbamazepine (CBZ) is a widely used antiepileptic drug effective in managing partial and generalized tonic-clonic seizures. Despite its established therapeutic efficacy, CBZ has been reported to worsen seizures in another form of epilepsy, generalized absence seizures, in both clinical and experimental settings. In this study, we focused on thalamic reticular (RT) neurons, which regulate thalamocortical network activity in absence seizures, to investigate whether CBZ alters their excitability, thereby contributing to the exacerbation of seizures. Using ex vivo whole-cell patch-clamp electrophysiology, we found that CBZ selectively inhibits the tonic firing of RT neurons in a dose-dependent manner without affecting burst firing. At the RT-thalamocortical (RT-TC) synapse, CBZ significantly increases the failure rate of GABAergic synaptic transmission, with greater effects on somatostatin (SST) – than parvalbumin (PV) - expressing RT neurons. In vivo EEG recordings and open-field behavior in Scn8amed+/-mouse model confirmed that CBZ treatment exacerbates absence seizures, increasing both seizure frequency and duration while reducing locomotor activity. In addition, CBZ further amplifies the pre-existing reduction in tonic firing of RT in Scn8amed+/-mice. These findings uncover a novel mechanism by which CBZ exacerbates absence seizures through selective inhibition of RT neuron excitability and disruption of GABAergic synaptic transmission. This work provides mechanistic insights into the paradoxical effects of CBZ and suggest potential avenues for optimizing epilepsy treatment strategies.

Scientific Significance

This study addresses the clinical paradox in which CBZ, a widely prescribed antiepileptic drug, paradoxically aggravates absence seizures. Understanding the cellular mechanisms behind this phenomenon is critical for improving epilepsy treatments. Here, using electrophysiology recordings from intact thalamocortical slices and SCN8amed+/-mice, an absence seizure animal model, we demonstrate that CBZ selectively inhibits tonic firing of RT neurons and their output to thalamocortical circuits, with a more pronounced effect in SCN8amed+/-mice. These novel findings provide a mechanistic explanation for CBZ’s paradoxical aggravation of absence seizures, offering a framework for understanding the pharmacological effects of other anti-epilepsy drugs and guiding the development of more effective therapeutic strategies for epilepsy.
Filamented Light (FLight) Bioprinting of Mini-Muscles with Self-Renewal Potential
Authors: Liu Hao , Winkelbauer Michael , Janiak Jakub , Kalkan Ali Kerem , Kim Inseon , Chansoria Parth , Bar-Nur Ori , Zenobi-Wong Marcy
Published: February 2025

The plasticity and regenerative capacity of skeletal muscle arise from quiescent stem cells activated upon overload, injury, or inflammation. Developingin vitromuscle models to study these properties could advance muscle disease modeling and pre-clinical evaluation. Here, we leverage Filamented Light (FLight) bioprinting as a high-throughput approach for producing mini-muscle tissues. Using Pax7-nGFP myoblasts, we bioprinted mini-muscles from pristine collagen-fibrinogen. The FLight hydrogel consisted of aligned microstructures which guided the formation of aligned myotubes. Mini-muscles demonstratedin vivo-like tissue organization, including highly aligned myotubes and a Pax7+cell pool embedded in newly deposited laminin. Both spontaneous and electrically stimulated contractions were observed. Collagen-fibrinogen matrix was promising for maintenance of the Pax7+cell pool. Damage from cardiotoxin-induced injury of the mini-muscles led to a massive proliferation of Pax7+cells and restoration of the contractile properties. Notably, small molecules such as Repsox could enhance regeneration. FLight printed mini-muscles have potential for applications in muscle biology, exercise/atrophy, disease models, and drug screening.
Principled PCA separates signal from noise in omics count data
Authors: Stanley Jay S. , Yang Junchen , Li Ruiqi , Lindenbaum Ofir , Kobak Dmitry , Landa Boris , Kluger Yuval
Published: February 2025

Principal component analysis (PCA) is indispensable for processing high-throughput omics datasets, as it can extract meaningful biological variability while minimizing the influence of noise. However, the suitability of PCA is contingent on appropriate normalization and transformation of count data, and accurate selection of the number of principal components; improper choices can result in the loss of biological information or corruption of the signal due to excessive noise. Typical approaches to these challenges rely on heuristics that lack theoretical foundations. In this work, we present Biwhitened PCA (BiPCA), a theoretically grounded framework for rank estimation and data denoising across a wide range of omics modalities. BiPCA overcomes a fundamental difficulty with handling count noise in omics data by adaptively rescaling the rows and columns – a rigorous procedure that standardizes the noise variances across both dimensions. Through simulations and analysis of over 100 datasets spanning seven omics modalities, we demonstrate that BiPCA reliably recovers the data rank and enhances the biological interpretability of count data. In particular, BiPCA enhances marker gene expression, preserves cell neighborhoods, and mitigates batch effects. Our results establish BiPCA as a robust and versatile framework for high-throughput count data analysis.
Defective pollen meiosis in Arabidopsis due to combined arabinan and galactan insufficiency
Authors: Kikuchi Takuma , Soga Kouichi , Kotake Toshihisa , Takahashi Daisuke
Published: February 2025

The development of pollen is critical or seed plants, and depends on precise cellular and molecular mechanisms. It is known that the cell wall plays a key role in the progression of pollen maturation. An earlier phase in pollen development is the meiosis of pollen mother cells (PMCs), the fundamental process for producing viable pollen grains. However, the significance of the cell wall during pre-meiosis processes has remained unclear. Pectin, a major component of the cell wall, is known to accumulate abundantly in pollen. To investigate the significance of the cell wall during pollen meiosis, we generated anarad1 gals2 gals3triple mutant ofArabidopsis thaliana, lacking the genes responsible for normal synthesis of arabinan and galactan, which constitute the side chains of pectin. Although vegetative growth and cell wall properties were comparable in wild-type (WT) andarad1 gals2 gals3, the pollen development in the mutant failed during meiosis. Immunohistochemical analysis showed that pectic arabinan and galactan accumulated in WT PMCs before meiosis, but this was not observed in mutant PMCs. We believe that this study is the first to demonstrate the critical role of cell wall components, specifically pectic arabinan and galactan, in the pre-meiosis processes of pollen development.

Highlight

Pectic arabinan and galactan accumulate on the surface of pollen mother cells and this accumulation is essential for pollen meiosis.
Gibberellin-deactivating GA2OX enzymes act as a hub for auxin-gibberellin crosstalk inArabidopsis thalianaroot growth regulation
Authors: Kubalová Monika , Griffiths Jayne , Müller Karel , Jones Alexander M. , Fendrych Matyáš
Published: February 2025

Plant bodies are built from immobile cells, making the regulation of cell expansion essential for growth, development, and adaptation. In roots, cell elongation executes the movement of the root tips through soil. This process is tightly controlled by numerous signaling pathways. Among these, gibberellin and auxin signaling stand out for their contrasting effects on root growth, interacting through complex crosstalk at multiple regulatory levels. Here we reveal the molecular basis of the auxin-gibberellin crosstalk in the model plantArabidopsis thaliana. We show that auxin signaling pathway steers the expression ofGIBBERELLIN 2-OXIDASES (GA2OX), key gibberellin-deactivating enzymes in the root elongation zone. GA2OX are negative regulators of root cell elongation;GA2OX8overexpression decreases gibberellin levels and inhibits root cell elongation, in contrast, thega2ox heptuplemutant roots show elevated gibberellin levels in the elongation zone and grow longer roots. Shoot derived auxin can regulateGA2OX8expression in roots, linking systemic auxin signaling to local gibberellin modulation. In addition,GA2OX8is active in vascular tissues and the stem cell niche, tissues with high auxin levels. Loss ofGA2OXgenes results in altered stem cell niche, including increased quiescent center size and expanded root cell layers, highlighting the role of these enzymes in maintaining tissue organization. Together, our findings identify GA2OX6 and GA2OX8 enzymes as key mediators of auxin-gibberellin crosstalk, providing insights into their roles in root elongation, vascular development, and stem cell niche maintenance. These results expand our understanding of how auxin integrates with gibberellin signaling to coordinate root development and growth dynamics.
Volatile-Mediated Plant Defense Networks: Field Evidence for Isoprene as a Short-Distance Immune Signal
Authors: Zhu Peiyuan , Weber Baris , Rosenkranz Maaria , Polle Andrea , Ghirardo Andrea , Muhr Jan , Vlot A. Corina , Schnitzler Jörg-Peter
Published: February 2025

Isoprene, the most abundant hydrocarbon emitted by vegetation, protects photosynthesis against oxidative and thermal stress and significantly impacts atmospheric chemistry. While laboratory studies suggest a role for isoprene in plant defense, its function in plant-plant communication under natural conditions remains unclear. Here, we demonstrate that isoprene acts as a signaling molecule, triggering systemic immune responses in neighboring plants against bacterial pathogens under field conditions. We established an experimental system using wild-type and transgenic silver birch (Betula pendula) lines engineered to emit varying levels of isoprene. Over two growing seasons, we examined the effects of birch-emitted volatile organic compounds on neighboring Arabidopsis thaliana, including wild-type and immune signaling mutants (llp1: legume lectin-like protein 1;jar1: jasmonate resistant 1). Isoprene emission rates positively correlated with systemic resistance in receiver plants, with higher emissions enhancing inhibition ofPseudomonas syringaegrowth. This immune response occurred independently of jasmonate signaling but required functional LLP1, suggesting a specific recognition pathway. By combiningArabidopsismutant responses with birch volatile profiles, we confirmed that isoprene, rather than other terpenoids, mediates this effect. These findings reveal an unrecognized ecological function of isoprene as an airborne immune signal, establishing transgenic birch as a robust model for studying volatile-mediated plant defense networks in natural environments. Our results provide new insights into the molecular mechanisms underlying plant volatile perception and expand our understanding of chemical communication in terrestrial ecosystems.

Significance Statement

Isoprene, the most abundant volatile organic compound released by plants, protects against abiotic stress. Here, we demonstrate that isoprene also functions under ambient atmosphere as a short-distance immune signal, enhancing neighboring plants’ resistance to bacterial pathogens. This finding reveals a putative ecological role of isoprene in plant defense networks and suggests strategies for sustainable agriculture and forest management under environmental stress.
The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity
Authors: Bigot Jeanne , Legendre Rachel , Hamroune Juliette , Jacques Sébastien , Legars Mathieu , Guillot Loïc , Corvol Harriet , Hennequin Christophe , Guitard Juliette , Coppée Jean-Yves , Balloy Viviane , Chica Claudia
Published: February 2025

Background

Innate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure toPseudomonas aeruginosaflagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression.

Results

By conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific factors (TFs) whose binding may drive this process.

Conclusions

In summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns
LoRA-DR-suite: adapted embeddings predict intrinsic and soft disorder from protein sequences
Authors: Lombardi Gianluca , Seoane Beatriz , Carbone Alessandra
Published: February 2025

Intrinsic disorder regions (IDR) and soft disorder regions (SDR) provide crucial information on a protein structure to underpin its functioning, interaction with other molecules and assembly path. Circular dichroism experiments are used to identify intrinsic disorder residues, while SDRs are characterized using B-factors, missing residues, or a combination of both in alternative X-ray crystal structures of the same molecule. These flexible regions in proteins are particularly significant in diverse biological processes and are often implicated in pathological conditions. Accurate computational prediction of these disordered regions is thus essential for advancing protein research and understanding their functional implications. To address this challenge, LoRA-DR-suite employs a simple adapter-based architecture that utilizes protein language models embeddings as protein sequence representations, enabling the precise prediction of IDRs and SDRs directly from primary sequence data. Alongside the fast LoRA-DR-suite implementation, we release SoftDis, a unique soft disorder database constructed for approximately 500,000 PDB chains. SoftDis is designed to facilitate new research, testing, and applications on soft disorder, advancing the study of protein dynamics and interactions.
A simple approach to multiplexed PCR amplicon sequencing of plumage-associated loci inVermivorawarblers
Authors: Toews David P. L. , Besch Catharine E.
Published: February 2025

The dynamics of hybridization between golden-winged (Vermivora chrysoptera) and blue-winged warblers (V. cyanoptera) has been of interest for over a century. Whole genome analysis found only a small number of genomic regions that differed between the species. We previously developed a restriction enzyme-based RFLP approach to genotype large numbers of individuals at each of these loci. Here we extend this approach to an amplicon sequencing method to genotype individuals at these six plumage-associated regions. We demonstrate the efficacy using preliminary data from 4 golden-winged and 4 blue-winged warblers as well as provide the data and scripts necessary to analyze these data for other interested in replicating this approach. Our hope is that these data are useful for other researchers interested in genotypingVermivorawarblers.

Additional methods

https://github.com/david-toews/vermivora_amplicon
Shear Stress Conditioning Promotes a Pro-Inflammatory Response in Porcine Endocardial Endothelial Cells
Authors: Ji Pengfei , Grande-Allen Kathryn Jane , Balaji Swathi , Birla Ravi K. , Keswani Sundeep G.
Published: February 2025

PURPOSE

Discrete subaortic stenosis (DSS) is a congenital heart disease characterized by a narrowing of the passage below the aortic valve in the left ventricular outflow tract (LVOT) [1]. While endocardial endothelial cells (EECs) are known to play a role in DSS, the response of these cells to shear stress is not known. In this study, we hypothesize that the response of EECs to shear stress in the LVOT is a mediator of DSS.

METHODS

To test this hypothesis, we conditioned porcine EECs to controlled shear stress regimes using cone and plate bioreactors. Subsequently, we quantified the concentration of proinflammatory cytokine in the conditioned media using the Luminex assay. Bulk-RNA sequencing was used to quantify changes in the genotype of the shear stress conditioned EECs.

RESULTS

The expression of CD31 was knocked down and subsequently, the changes in release of shear stress induced proinflammatory cytokines released by EECs quantified using the Luminex assay. The results of these studies show that the inflammatory cytokines were highly selected in the conditioning medium, and under bioreactor treatment the cell activated the PI3K-AKT and TNF-a signaling, which also triggered the other immune cell responses though Th1, Th2 and Th17 cell differentiation pathways. Furthermore, CD31 was identified as a mediator of the pro-inflammatory response of shear stress conditioned EECs.

CONCLUSIONS

The studies provide a clear link between shear stress, and the subsequent proinflammatory response of EECs as a mediator of DSS.
Larval development habitats of Culicoides midges in the western United States
Authors: Barbera Carly , Mayo Christie , Perkins Alex , Rohr Jason R.
Published: February 2025

Culicoides midges are vectors of bluetongue virus (BTV), an arbovirus affecting wild and domestic ruminants. Bluetongue distribution generally overlaps with vector range, so understanding the ecology of the vector is necessary for predicting BTV risk. Culicoides require moist substrate for oviposition and development, and C. sonorensis, the primary vector in the western United States, is classically associated with livestock wastewater ponds. However, it is well-known that BTV can be found outside of managed livestock areas, with transmission also occurring in natural settings. To better classify development habitat for Culicoides, we conducted a broad biweekly survey of moist and wet habitats from June to September of 2022 in northern Colorado at ten sites, including large livestock operations, non-commercial domestic operations, and natural spaces. Samples were maintained in the insectary for 11 weeks and monitored for emergence of adult midges. Standing water substrates displayed higher presence and abundance of midges than running or transient habitats, though all microhabitats showed emergence. Additionally, livestock sites did not produce more midges than other site types, and in fact more midges were observed in natural spaces per sample and overall. Livestock spaces did, however, show significantly higher proportions of C. sonorensis midges, which are thought to be the most competent vectors of BTV in this region. These results suggest that development sites in natural areas may play an important role in maintaining vector populations in the western U.S. outside of previously implicated livestock operations, and that differences in larval habitat lead to differences in vector species composition.
Mitochondrial metabolism is rapidly re-activated in mature neutrophils to support stimulation-induced response
Authors: Lika Jorgo , Votava James A. , Datta Rupsa , Kralovec Aleksandr M. , Smith Frances M. , Huttenlocher Anna , Skala Melissa C. , Fan Jing
Published: February 2025

Neutrophils are highly abundant innate immune cells that are constantly produced from myeloid progenitors in the bone marrow. Differentiated neutrophils can perform an arsenal of effector functions critical for host defense. This study aims to quantitatively understand neutrophil mitochondrial metabolism throughout differentiation and activation, and to elucidate the impact of mitochondrial metabolism on neutrophil functions. To study metabolic remodeling throughout neutrophil differentiation, murine ER-Hoxb8 myeloid progenitor-derived neutrophils and human induced pluripotent stem cell-derived neutrophils were assessed as models. To study the metabolic remodeling upon neutrophil activation, differentiated ER-Hoxb8 neutrophils and primary human neutrophils were activated with various stimuli, including ionomycin, MSU crystals, and PMA. Characterization of cellular metabolism by isotopic tracing, extracellular flux analysis, metabolomics, and fluorescence-lifetime imaging microscopy revealed dynamic changes in mitochondrial metabolism. As neutrophils mature, mitochondrial metabolism decreases drastically, energy production is fully offloaded from oxidative phosphorylation, and glucose oxidation through TCA cycle is substantially reduced. Nonetheless, mature neutrophils retain the capacity for mitochondrial metabolism. Upon stimulation with certain stimuli, TCA cycle is rapidly activated. Mitochondrial pyruvate carrier inhibitors reduce this re-activation of the TCA cycle and inhibit the release of neutrophil extracellular traps. Mitochondrial metabolism also impacts neutrophil redox status, migration, and apoptosis without significantly changing overall bioenergetics. Together, these results demonstrate that mitochondrial metabolism is dynamically remodeled and plays a significant role in neutrophil function and fate. Furthermore, these findings point to the therapeutic potential of mitochondrial pyruvate carrier inhibitors in a range of conditions where dysregulated neutrophil response drives inflammation and contributes to pathology.
Improved Spatial Transcriptomics Clustering with Nested Graph Neural Networks
Authors: Jain Atishay , Laidlaw David H. , Ma Ying , Singh Ritambhara
Published: February 2025

We introduce a novel approach, STING, for spatial transcriptomic clustering analysis. Unlike existing state-of-the-art techniques that use graph-based neural networks (GNNs) trained on graphs generated from the spatial proximity of tissue locations (or spots), STING incorporates spot-specific related genes. This feature allows STING to better distinguish between clusters and identify meaningful gene-gene relations for knowledge discovery. It is a nested GNN framework that simultaneously models gene-gene and spatial relations. Using the gene expression, we generate a spot-specific gene-gene co-expression graph. We implement an inner GNN for these graphs to generate embeddings for each location. Next, we utilize these embeddings as features in a sample-wide graph generated using spatial information. We implement an outer GNN for this graph to reconstruct the original gene expression data. Finally, STING is trained end-to-end to generate embeddings that capture gene-gene and spatial information, which we input to a clustering algorithm to produce the spatial clusters. Experiments for 26 samples across 7 datasets and 5 spatial sequencing technologies show that STING outperforms the existing state-of-the-art techniques with a 1.58% to 4.07% improvement in the clustering evaluation metric, thus confirming that integrating gene-gene relation information with the clustering task leads to more informative embeddings and better clusters. Furthermore, experiments on a human breast cancer dataset show that STING identifies relevant genes and gene-gene relations, enabling biological hypothesis generation.
Single-cell RNA-seq reveals altered plasma cell subsets and decreased cytotoxicity of NK cells in patients with Kawasaki disease
Authors: Zhou Yuanlin , Liu Yan , Liu Li , Shen Xiaojia , Wen Xiaobin , Lin Guixu , Tang Lin , Li Qian , Gan Jingqiu , Li Ruixu , Shang Jin , Li Lei
Published: February 2025

Aim

The pathogenesis and therapeutic strategies of Kawasaki disease (KD) are worth further exploring. Using single-cell RNA sequencing (scRNA-seq), our study aimed to explore the landscape of peripheral blood mononuclear cells (PBMCs) in patients with KD.

Methods

We analyzed the scRNA-seq data of three patients with KD and three healthy controls from the GSE168732 dataset. Additionally, we explored the immune profiles and immune cell subtypes of patients with KD.

Results

Significantly increased B cells and decreased NK cells were observed in the KD group compared with that in the control group. Furthermore, six B cell subsets were identified in the PBMCs of patients with KD. Particularly, plasma cells (CD9+and S100A9+B cell clusters) distinctly increased in the KD group. CD9+B cell cluster was characterized by vascular endothelial growth factor (VEGF) signaling-associated marker genes and DEGs. Meanwhile the S100A9+B cell cluster was characterized by platelet aggregation marker genes. As for NK cells, CD16+CD56dimNK cells were enriched in the KD group. Cytotoxicity-related activating receptors (KLRD1,KLRC3) and cytotoxicity-associated genes (PRF1, NKG7, GZMA, GZMH, GNLY) were downregulated in the KD group.

Conclusion

CD9+and S100A9+plasma cells may contribute to CALs in KD by upregulating VEGF and activating platelet. In addition, decreased cytotoxicity of NK cells mediated by KLRD1/KLRC3 receptor may play a vital role in the development of KD. Our results suggested that plasma cells and NK cells could be promising targets for the treatment of KD.
Anti-Diabetic Effects ofNigella sativa and Cichorium intybusin Animal Experimental Model
Authors: Kashif Muhammad , Nasir Amar , Aziz Muhammad Khizer , ur Rehman Aziz , Vincent Tom , Gonzalez Jean-Paul , Waheed Usman
Published: February 2025

Diabetes mellitus is a chronic metabolic disease in humans associated with severe complications with a significant impact on the health, life expectancy, and lifestyle of patients.

The present study has been designed to examine the anti-hyperglycemic efficacy of two medicinal plants -Nigella sativaseeds andCichorium intybusleaves - and their combined effects on body weight and hematological/serological parameters in alloxan-induced diabetic rabbits.

For this purpose, 30 adult rabbits were divided into six equal groups of five rabbits each. Group I was kept as the negative control, while all other groups received a single intravenous injection of alloxan monohydrate to induce diabetes: Group II as positive control; Group III received metformin hydrochloride; Group IV was fed powderedC. intybusplant leaves; Group V was givenN. sativaaqueous seeds extract; and Group VI was fed a combination ofC. intybusandN. sativa. Fasting blood glucose levels and body weight of rabbits were observed at 0 days (before treatment) to Day 28 and regularly monitored during the four-week experimental trial. Biochemical analysis, serum insulin level, and hematological parameters were measured at the end of the experiment.

Results showed thatC. intybus, N. sativa, and their mixture significantly (p< 0.05) decreased the blood glucose levels, urea and creatinine levels, and enzyme levels in the blood. At the same time, body weight gain, red blood cell (RBC) count, white blood cell (WBC) count, and packed cell volume (PCV) % were increased in diabetic rabbits as compared with positive control rabbits. It was concluded that these plants have potential hypoglycemic effects and reduced diabetic complications in alloxan-induced diabetic rabbits. Further studies are needed to understand their potential for antidiabetic remedy.
Immune-induced TCR-like antibodies regulate specific T cell response
Authors: Kishida Kazuki , Kawakami Keisuke , Tanabe Hiroaki , Nakai Wataru , Yonekura Koji , Yokoyama Shigeyuki , Arase Hisashi
Published: February 2025

Antigen-specific regulation of T cell response is crucial for limiting hyperimmune response. In this study, we discovered that antibodies specific to the antigen peptide-MHC class II complex are produced during helper T cell responses to various antigens. These antibodies specifically inhibited T cell receptor (TCR) recognition of MHC class II molecules presenting specific antigen peptide. We have termed these antibodies ‘immuneinduced TCR-like antibodies’ (iTabs). Immunization with peptides containing flanking residues induced iTabs, whereas immunization with peptides lacking flanking residues did not. Furthermore, immunization of iTab-inducible peptide as well as iTab treatment suppressed autoimmune disease development. Our findings provide a strategy for suppressing antigen-specific helper T cell responses using specific peptides, potentially controlling autoimmune diseases.