Front Immunol. 2025 Apr 9;16:1509805. doi: 10.3389/fimmu.2025.1509805. eCollection 2025.

ABSTRACT

INTRODUCTION: Uveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.

METHODS: In this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.

RESULTS: Modular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-β, IFN-γ, β, and α) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature's discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.

CONCLUSION: These findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis.

PMID:40270958 | PMC:PMC12014655 | DOI:10.3389/fimmu.2025.1509805

Front Public Health. 2025 Apr 9;13:1459060. doi: 10.3389/fpubh.2025.1459060. eCollection 2025.

ABSTRACT

Nowadays, heavy metal (HM) contamination and their ecological risk in coastal sediments are global issues. This research provides insight into the heavy metals' contamination, source apportionment, and potential ecological risks in the surface sediments of the Xiang-Shan wetland in Taiwan, which is undergoing rapid economic development, mainly by the semiconductor industries. The levels of twelve metals and total organic matter (TOM) were measured in 44 samples of surface sediment during the spring and winter seasons of 2022. Subsequently, the single and comprehensive pollution indices were assessed. The findings showed that the average of HM contents exhibited a descending sequence of Al > Fe > Mn > Zn > Co > Ga > Cr > Cu > In > Ni > Pb = Cd during both seasons. The E f , I geo , and PI showed that the majority of sediment samples were uncontaminated to heavily contaminated by Fe, Al, Zn, Cu, Mn, Cr, Ni, Co and Ga, and extremely contaminated by In. Moreover, PLI and mC deg unveiled that the surface sediments of DJ, OB, and KY stations were strongly or extremely polluted. PERI revealed that the sediment shows minimal to moderate ecological risk. The findings of multivariate analyses suggested that Fe, Al, Cu, Zn, and Ni derived from natural sources, while Ga, In, Co, Cr, and Mn originated from both anthropogenic and natural origins. Hence, it is critical that HM contamination, particularly Co, In, and Ga, be continuously monitored in the study area. Our data provide significant insights for more effective prevention and evaluation of HM contamination in the aquatic-sedimentary ecosystems of Taiwan.

PMID:40270744 | PMC:PMC12014647 | DOI:10.3389/fpubh.2025.1459060

MicroPubl Biol. 2025 Apr 8;2025. doi: 10.17912/micropub.biology.001567. eCollection 2025.

ABSTRACT

We examined the effects of X-ray irradiation on Xenopus laevis , focusing on pre- and post-fertilization exposure. We applied X-ray doses of 10, 50, 100, 250, and 500 Gy. Fifty percent of the 360 eggs irradiated at 250 Gy failed to fertilize, while fertilized eggs developed normally until the gastrula stage. Doses ranging from 10 to 250 Gy caused developmental anomalies. High mortality rates were observed at doses of 100 to 500 Gy. Post-fertilization irradiation at 50 to 100 Gy resulted in 100% lethality, while exposure to 10 Gy led to only 13% lethality, although both exposure levels produced similar types of developmental anomalies compared to pre-fertilization irradiation. This study highlights how the timing and intensity of exposure critically affect embryo viability, especially during the sensitive stages of fertilization and gastrulation. We establish the necessary and sufficient dosage to further investigate the molecular mechanisms of X-ray damage to DNA and protein.

PMID:40270682 | PMC:PMC12015645 | DOI:10.17912/micropub.biology.001567

Front Mol Biosci. 2025 Apr 9;12:1557835. doi: 10.3389/fmolb.2025.1557835. eCollection 2025.

ABSTRACT

The human protein kinome is a group of over 500 therapeutically relevant kinases. Exemplified by over 10,000 phosphorylated sites reported in global phosphoproteomes, kinases are also highly regulated by phosphorylation. Currently, 1008 phosphorylated sites in 273 kinases are associated with their regulation of activation/inhibition, and a few in 30 kinases are associated with altered activity. Phosphorylated sites in 196 kinases are related to other molecular functions such as localization and protein interactions. Over 8,000 phosphorylated sites, including all those in 517 kinases are unassigned to any functions. This imposes a significant bias and challenge for the effective analysis of global phosphoproteomics datasets. Hence, we derived a set of stably and frequently detected phosphorylated sites (representative phosphorylated sites) across diverse experimental conditions annotated in the PhosphoSitePlus database and presumed them to be relevant to the human kinase regulatory network. Analysis of these representative phosphorylated sites led to the classification of 449 kinases into four distinct categories (kinases with phosphorylated sites apportioned (PaKD) and enigmatic (PeKD), and those with predominantly within kinase domain (PiKD) and outside kinase domain (PoKD)). Knowledge-based functional analysis and sequence conservation across the family/subfamily identified phosphorylated sites unique to specific kinases that could contribute to their unique functions. This classification of representative kinase phosphorylated sites enhance our understanding of prioritized validation and provides a novel framework for targeted phosphorylated site enrichment approaches. Phosphorylated sites in kinases associated with dysregulation in diseases were frequently located outside the kinase domain, and suggesting their regulatory roles and opportunities for phosphorylated site-directed therapeutic approaches.

PMID:40270594 | PMC:PMC12015135 | DOI:10.3389/fmolb.2025.1557835

Bioact Mater. 2025 Apr 14;50:246-272. doi: 10.1016/j.bioactmat.2025.04.008. eCollection 2025 Aug.

ABSTRACT

We produced a microstructured, electroconductive and nano-functionalized drug eluting cardiac patch (MENDEP) designed to attract endogenous precursor cells, favor their differentiation and counteract adverse ventricular remodeling in situ. MENDEP showed mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced impedance, controlled biodegradability, molecular recognition ability and controlled drug release activity. In vitro, cytocompatibility and cardioinductivity were demonstrated. Migration tests showed the chemoattractive capacity of the patches and conductivity assays showed unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially implanted in a rat model of ischemia/reperfusion (I/R). Histological, immunofluorescence and biomarker analysis indicated that implantation did not cause damage to the healthy myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and triggered their differentiation towards the vascular lineage. Under the patch, the myocardial tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in the patch group. Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface of the left ventricle over 4-week implantation period, underwent progressive vascularization, did not perturb the healthy myocardium and showed great potential in repairing the infarcted area.

PMID:40270551 | PMC:PMC12017858 | DOI:10.1016/j.bioactmat.2025.04.008

J Diabetes. 2025 Apr;17(4):e70090. doi: 10.1111/1753-0407.70090.

ABSTRACT

AIM: Circulating Gremlin 2 (Grem2) has recently been linked to human obesity, but its role in type 2 diabetes (T2D) remains unclear. This study aims to explore the association of circulating Grem2 with β-cell function.

METHODS: A post hoc analysis was conducted using data from three clinical trials, in which all participants underwent the oral glucose tolerance test (OGTT). Circulating Grem2 levels were measured at 0, 1, and 2 h during the OGTT. In Trial 1, Grem2 levels were compared between participants with T2D (n = 59) and without T2D (n = 119). We further examined changes in Grem2 levels in response to oral antidiabetic drugs in participants with T2D in Trial 2 (n = 67) and calorie restriction in participants with prediabetes in Trial 3 (n = 231). The relationship between Grem2 levels and β-cell function was analyzed across all trials.

RESULTS: Fasting and 1-h Grem2 levels were lower in participants with T2D compared with those without T2D (728 ± 25 vs. 649 ± 31 pg/mL, p = 0.020; 631 ± 26 vs. 537 ± 31 pg/mL, p = 0.007). Fasting Grem2 levels were restored after antidiabetic treatment (550 ± 12 vs. 575 ± 12 pg/mL, p = 0.019), and 1-h Grem2 levels increased following calorie restriction (1118 ± 89 vs. 1144 ± 90 vs. 1253 ± 89 pg/mL, p for trend = 0.002). The 1-h Grem2 levels were positively associated with β-cell function assessed by the oral disposition index and HOMA-β.

CONCLUSION: Reduced circulating Grem2 levels are associated with impaired β-cell function in T2D, and could be restored through antidiabetic interventions.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01959984, NCT01758471, NCT03856762.

PMID:40270326 | DOI:10.1111/1753-0407.70090

Plant Physiol. 2025 Mar 28;197(4):kiaf107. doi: 10.1093/plphys/kiaf107.

ABSTRACT

Elevated temperatures resulting from climate change adversely affect natural and crop ecosystems, necessitating the development of heat-tolerant crops. Here, we established a framework to precisely identify protein phosphorylation sites associated with varying temperature sensitivities in wheat (Triticum aestivum). We identified specific kinases primarily associated with particular temperatures, but our results also suggest a striking overlap between cold and heat signaling. Furthermore, we propose that the phosphorylation state of a specific set of proteins may represent a signature for heat stress tolerance. These findings can potentially aid in the identification of targets for breeding or genome editing to enhance the sub- and supra-optimal temperature tolerance of crops.

PMID:40270188 | DOI:10.1093/plphys/kiaf107

Biol Sex Differ. 2025 Apr 23;16(1):28. doi: 10.1186/s13293-025-00707-6.

ABSTRACT

Gonadal testosterone stimulates skeletal muscle anabolism and contributes to sexually differentiated adipose distribution through incompletely understood mechanisms. Observations in humans and animal models have indicated a major role for androgen receptor (AR) in mediating sex differences in body composition throughout the lifespan. Traditional surgical, genetic and pharmacological studies have tested systemic actions of circulating androgens, and more recent transgenic approaches have allowed for tests of AR gene function in specific androgen responsive niches contributing to body composition, including: skeletal muscle and surrounding interstitial cells, white and brown adipose, as well as trabecular and cortical bone. Less well understood is how these functions of gonadal androgens interact with exercise. Here, we summarize the understood mechanisms of action of AR and its interactions with exercise, specifically on outcomes of body composition and muscle function, and the global- and tissue-specific role of AR in regulating skeletal muscle, adipose, and bone morphology. Additionally, we describe the known effects of androgen and AR manipulation on female body composition, muscle morphology, and sport performance, while highlighting a need for greater inclusion of female subjects in human and animal muscle physiology and endocrinology research.

PMID:40269952 | DOI:10.1186/s13293-025-00707-6

J Pept Sci. 2025 Jun;31(6):e70020. doi: 10.1002/psc.70020.

ABSTRACT

Peptide-based therapeutics have gained attention in cancer treatment because of their good specificity, low toxicity, and ability to modulate immune responses. However, challenges such as enzymatic degradation and poor bioavailability limit their clinical application. Peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) systems have emerged as a transformative platform in cancer therapy that offers unique advantages, including enhanced stability, sustained release, and precise delivery of therapeutic agents. This review highlights the synergistic integration of peptides with PLGA and addresses key challenges of peptide-based therapeutics. The application of peptide-functionalized PLGA systems encompasses a diverse range of strategies for cancer therapy. In chemotherapy, peptides disrupt critical tumor pathways, induce apoptosis, and inhibit angiogenesis, demonstrating their versatility in targeting various aspects of tumor progression. In immunotherapy, peptides act as antigens to stimulate robust immune responses or as immune checkpoint inhibitors to restore T cell activity, overcoming tumor immune evasion. These systems also harness the enhanced permeability and retention effect, facilitating preferential accumulation in tumor tissues while leveraging tumor microenvironment (TME)-responsive mechanisms, such as pH-sensitive or enzyme-triggered drug release, to achieve controlled, localized delivery. Collectively, peptide-functionalized PLGA systems represent a promising, versatile approach for precise cancer therapy that integrates innovative delivery strategies with highly specific, potent therapeutic agents.

PMID:40269479 | DOI:10.1002/psc.70020

Environ Microbiol Rep. 2025 Apr;17(2):e70088. doi: 10.1111/1758-2229.70088.

ABSTRACT

The Amazon rainforest has been subjected to high rates of deforestation, mostly for pasturelands, over the last few decades. This change in plant cover is known to alter the soil microbiome and the functions it mediates, but the genomic changes underlying this response are still unresolved. In this study, we used a combination of deep shotgun metagenomics complemented by a supervised machine learning approach to compare the metabolic strategies of tropical soil microbial communities in pristine forests and long-term established pastures in the Amazon. Machine learning-derived metagenome analysis indicated that microbial community structures (bacteria, archaea and viruses) and the composition of protein-coding genes were distinct in each plant cover type environment. Forest and pasture soils had different genomic diversities for the above three taxonomic groups, characterised by their protein-coding genes. These differences in metagenome profiles in soils under forests and pastures suggest that metabolic strategies related to carbohydrate and energy metabolisms were altered at community level. Changes were also consistent with known modifications to the C and N cycles caused by long-term shifts in aboveground vegetation and were also associated with several soil physicochemical properties known to change with land use, such as the C/N ratio, soil temperature and exchangeable acidity. In addition, our analysis reveals that these alterations in land use can also result in changes to the composition and diversity of the soil DNA virome. Collectively, our study indicates that soil microbial communities shift their overall metabolic strategies, driven by genomic alterations observed in pristine forests and long-term established pastures with implications for the C and N cycles.

PMID:40269473 | DOI:10.1111/1758-2229.70088

Nat Plants. 2025 Apr 23. doi: 10.1038/s41477-025-01978-y. Online ahead of print.

ABSTRACT

Ferns are essential for understanding plant evolution; however, their large and intricate genomes have kept their genetic landscape largely unexplored, with only a few genomes sequenced and limited transcriptomic data available. To bridge this gap, we generated extensive RNA-sequencing data across various organs from 22 representative fern species, resulting in high-quality transcriptome assemblies. These data enabled us to construct a time-calibrated phylogeny for ferns, encompassing all major clades, which revealed numerous instances of whole-genome duplication. We highlighted the distinctiveness of fern genetics, discovering that half of the identified gene families are unique to ferns. Our exploration of fern cell walls through biochemical and immunological analyses uncovered the presence of the lignin syringyl unit, along with evidence of its independent evolution in ferns. Additionally, the identification of an unusual sugar in fern cell walls suggests a divergent evolutionary trajectory in cell wall biochemistry, probably influenced by gene duplication and sub-functionalization. To facilitate further research, we have developed an online database that includes preloaded genomic and transcriptomic data for ferns and other land plants. We used this database to demonstrate the independent evolution of lignocellulosic gene modules in ferns. Our findings provide a comprehensive framework illustrating the unique evolutionary journey ferns have undertaken since diverging from the last common ancestor of euphyllophytes more than 360 million years ago.

PMID:40269175 | DOI:10.1038/s41477-025-01978-y

NPJ Precis Oncol. 2025 Apr 24;9(1):117. doi: 10.1038/s41698-025-00907-8.

ABSTRACT

Triple-negative breast cancer (TNBC) accounts for approximately 15% of all Breast Cancer (BC) cases with poorer prognosis and clinical outcomes compared to other BC subtypes due to greater tumor heterogeneity and few therapeutically targetable oncogenic drivers. To reveal actionable pathways for anti-cancer treatment, we use a proteomic approach to quantitatively compare the abundances of 6306 proteins across 55 formalin-fixed and paraffin-embedded (FFPE) TNBC tumors. We identified four major TNBC clusters by unsupervised clustering analysis of protein abundances. Analyses of clinicopathological characteristics revealed associations between the proteomic profiles and clinical phenotypes exhibited by each subtype. We validate the findings by inferring immune and stromal cell type composition from genome-wide DNA methylation profiles. Finally, quantitative proteomics on TNBC cell lines was conducted to identify in vitro models for each subtype. Collectively, our data provide subtype-specific insights into molecular drivers, clinicopathological phenotypes, tumor microenvironment (TME) compositions, and potential pharmacologic vulnerabilities for further investigations.

PMID:40269124 | DOI:10.1038/s41698-025-00907-8

Nat Commun. 2025 Apr 23;16(1):3811. doi: 10.1038/s41467-025-58912-1.

ABSTRACT

Cells move directionally along gradients of substrate stiffness - a process called durotaxis. In the situations studied so far, durotaxis relies on cell-substrate focal adhesions to sense stiffness and transmit forces that drive directed motion. However, whether and how durotaxis can take place in the absence of focal adhesions remains unclear. Here, we show that confined cells can perform durotaxis despite lacking focal adhesions. This durotactic migration depends on an asymmetric myosin distribution and actomyosin retrograde flow. We propose that the mechanism of this focal adhesion-independent durotaxis is that stiffer substrates offer higher friction. We put forward a physical model that predicts that non-adherent cells polarise and migrate towards regions of higher friction - a process that we call frictiotaxis. We demonstrate frictiotaxis in experiments by showing that cells migrate up a friction gradient even when stiffness is uniform. Our results broaden the potential of durotaxis to guide any cell that contacts a substrate, and they reveal a mode of directed migration based on friction. These findings have implications for cell migration during development, immune response and cancer progression, which usually takes place in confined environments that favour adhesion-independent amoeboid migration.

PMID:40268931 | DOI:10.1038/s41467-025-58912-1

Nat Commun. 2025 Apr 24;16(1):3843. doi: 10.1038/s41467-025-59170-x.

ABSTRACT

The discovery of N6-methyladenine (6mA) in eukaryotic genomes, typically found in prokaryotic DNA, has revolutionized epigenetics. Here, we show that symmetric 6mA is essential in the early diverging fungus Rhizopus microsporus, as the absence of the MT-A70 complex (MTA1c) responsible for this modification results in a lethal phenotype. 6mA is present in 70% of the genes, correlating with the presence of H3K4me3 and H2A.Z in open euchromatic regions. This modification is found predominantly in nucleosome linker regions, influencing the nucleosome positioning around the transcription start sites of highly expressed genes. Controlled downregulation of MTA1c reduces symmetric 6mA sites affecting nucleosome positioning and histone modifications, leading to altered gene expression, which is likely the cause of the severe phenotypic changes observed. Our study highlights the indispensable role of the DNA 6mA in a multicellular organism and delineates the mechanisms through which this epigenetic mark regulates gene expression in a eukaryotic genome.

PMID:40268918 | DOI:10.1038/s41467-025-59170-x

Mol Plant Microbe Interact. 2025 Apr 23. doi: 10.1094/MPMI-04-25-0036-R. Online ahead of print.

ABSTRACT

Plants are sessile organisms and must accurately respond to a host variety of growth, developmental, and environmental signals throughout their life to maximize fitness. Plant cell surface receptor-like kinases are ideal for the perception of such signals and their transduction within the cell. The Strubbelig Receptor Family (SRF) is a group of leucine-rich repeat receptor-like kinases, several of which have unknown function. Here, we identify a role for SRF6 in the perception of cell wall damage and the activation of downstream immune responses. We show that SRF6 is necessary for proper immune responses following elicitation with a short-chain oligogalacturonic acid, including activation of defense genes and increased bacterial resistance. We also demonstrated the srf6 mutants are more sensitive to isoxaben treatment, suggesting enhanced cell wall integrity maintenance responses. These findings are compatible with the hypothesis that cell wall integrity maintenance responses are elevated when pattern-triggered immunity is compromised.

PMID:40268881 | DOI:10.1094/MPMI-04-25-0036-R

Anal Chem. 2025 Apr 23. doi: 10.1021/acs.analchem.5c00847. Online ahead of print.

ABSTRACT

Point-of-care testing (POCT) for urinary tract infection (UTI) holds significant importance in the field of disease prevention and control, as well as the advancement of personalized precision medicine. However, conventional methods for detecting UTIs continue to face challenges such as time-consuming and labor-intensive detection processes, and reliance on specialized equipment and personnel rendering them unsuitable for point-of-care applications, especially in resource-limited areas. Here, we propose a novel flexible programmable manually powered microfluidic (FPM) for rapid point-of-care diagnosis of UTIs. For the first time, the proposed FPMs was achieved through a combined strategy of laser printing, cutting, and laminating, with the entire process completed in under 15 min at a cost of less than $0.5, which effectively circumvent the traditionally time-consuming and labor-intensive soft lithography techniques. By incorporating a modular structure-based design concept, we successfully developed various types of portable FPMs with functionalities including parallel pumping, simultaneous releasing, quantitative dispensing, sequential releasing, cyclic motion of multiple liquids and concentration gradient generating. As a proof-of-concept demonstration, we initially employed a high-throughput parallel dispensing design to analyze six urinary biochemical markers within 1 min, presenting potential applicability for future at-home testing. We then integrated a manually powered concentration gradient generator with spatial confinement signal enhancement to enable rapid phenotypic antimicrobial susceptibility testing (AST) within three to 5 h, while achieving clinical diagnostic accuracy rates of up to 95.56%. Therefore, our proposed FPMs eliminate the need for external pumps or actuators and could serve as an affordable hand-held POCT tool for UTI diagnosis. Moreover, in resource-poor areas, they have potential utility as robust POCT devices addressing diverse rapid detection needs.

PMID:40268684 | DOI:10.1021/acs.analchem.5c00847

J Appl Microbiol. 2025 Apr 23:lxaf099. doi: 10.1093/jambio/lxaf099. Online ahead of print.

ABSTRACT

AIMS: This study aimed to determine the antibiofilm properties of Klebsiella pneumoniae phages previously isolated from Thai hospital sewage water. Furthermore, we aimed to develop a phage-embedded and coated alginate hydrogel, suitable as a wound dressing or surface coating to prevent K. pneumoniae proliferation and biofilm formation.

METHODS AND RESULTS: The biofilm forming capacity of six clinical K. pneumoniae isolates was determined by means of the crystal violet assay and four strains which exhibited strong adherence were selected for further characterisation. Two phages (vB_KpnA_GBH014 and vB_KpnM_GBH019) were found to both significantly prevent (P = <0.0005) and disrupt (P = <0.05) biofilms produced by their K. pneumoniae hosts as determined by optical density readings using the crystal violet assay. Furthermore, alginate layers embedded and coated with phages vB_KpnA_GBH014 and vB_KpnM_GBH019 produced antibiofilm surfaces. Viable counts of recovered biofilms showed that alginate hydrogels containing phage vB_KpnA_GBH014 or vB_KpnM_GBH019 were associated with significantly fewer K. pneumoniae versus no-phage controls (1.61×108 cfu ml-1 vs 1.67×104 cfu ml-1, P = <0.005 and 1.78×108 cfu ml-1 vs 6.11×102 cfu ml-1, P = <0.00005, respectively). Confocal microscopy further revealed a significant reduction in the biovolume of biofilms formed on phage embedded and coated alginate hydrogels compared to no-phage controls.

CONCLUSIONS: Phages vB_KpnA_GBH014 and vB_KpnM_GBH019 can both prevent and disrupt biofilms produced by clinical isolates of K. pneumoniae. Embedding and coating these phages into alginate produces an antibiofilm matrix which may have promise for coating medical devices or as a wound dressing.

PMID:40268347 | DOI:10.1093/jambio/lxaf099

Cell Syst. 2025 Apr 17:101264. doi: 10.1016/j.cels.2025.101264. Online ahead of print.

ABSTRACT

We present the "spatial transcriptomics imaging framework" (STIM), an imaging-based computational framework focused on visualizing and aligning high-throughput spatial sequencing datasets. STIM is built on the powerful, scalable ImgLib2 and BigDataViewer (BDV) image data frameworks and thus enables novel development or transfer of existing computer vision techniques to the sequencing domain characterized by datasets with irregular measurement-spacing and arbitrary spatial resolution, such as spatial transcriptomics data generated by multiplexed targeted hybridization or spatial sequencing technologies. We illustrate STIM's capabilities by representing, interactively visualizing, 3D rendering, automatically registering, and segmenting publicly available spatial sequencing data from 13 serial sections of mouse brain tissue and from 19 sections of a human metastatic lymph node. We demonstrate that the simplest alignment mode of STIM achieves human-level accuracy.

PMID:40267922 | DOI:10.1016/j.cels.2025.101264

PLoS Comput Biol. 2025 Apr 23;21(4):e1013011. doi: 10.1371/journal.pcbi.1013011. Online ahead of print.

ABSTRACT

Animal acoustic communication contains many structural features. Among these, temporal structure, or rhythmicity, is increasingly tested empirically and modelled quantitatively. Accelerando is a rhythmic structure which consists of temporal intervals increasing in rate over a sequence. Why this particular vocal behaviour is widespread in many different animal lineages, and how it evolved, is so far unknown. Here, we use evolutionary game theory and computer simulations to link two rhythmic aspects of animal communication, synchronization and overlap: We test whether rhythmic accelerando could evolve under a pressure for acoustic overlap in time. Our models show that higher acceleration values result in a higher payoff, driven by the higher relative overlap between sequences. The addition of a cost to the payoff matrix models a physiological disadvantage to high acceleration rates and introduces a divergence between an individual's incentive and the overall payoff of the population. Analysis of the invasion dynamics of acceleration strategies shows a stable, non-invadable range of strategies for moderate acceleration levels. Our computational simulations confirm these results: A simple selective pressure to maximise the expected overlap, while minimising the associated physiological cost, causes an initially isochronous population to evolve towards producing increasingly accelerating sequences until a population-wide equilibrium of rhythmic accelerando is reached. These results are robust to a broad range of parameter values. Overall, our analyses show that if overlap is beneficial, emergent evolutionary dynamics allow a population to gradually start producing accelerating sequences and reach a stable state of moderate acceleration. Finally, our modelling results closely match empirical data recorded from an avian species showing rhythmic accelerando, the African penguin. This shows the productive interplay between theoretical and empirical biology.

PMID:40267164 | DOI:10.1371/journal.pcbi.1013011

STAR Protoc. 2025 Apr 22;6(2):103786. doi: 10.1016/j.xpro.2025.103786. Online ahead of print.

ABSTRACT

Crabtree-positive yeasts rapidly consume glucose via glycolysis, making it difficult to experimentally estimate their actual glycolytic rate or flux. We present a stable isotope labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based protocol to quantitatively estimate glycolytic and related carbon metabolic fluxes using Saccharomyces cerevisiae. This approach defines time windows to capture glucose metabolic intermediate production before label saturation, enabling a comparison of glycolytic flux changes across different cells. This protocol provides a reliable, quantitative approach to study dynamic metabolic fluxes in these cells. For complete details on the use and execution of this protocol, please refer to Vengayil et al., 2024.1.

PMID:40266845 | DOI:10.1016/j.xpro.2025.103786