Sci Rep. 2025 Jun 4;15(1):19528. doi: 10.1038/s41598-025-04273-0.

ABSTRACT

Fatty acids, particularly those derived from plant and animal oils, play roles in physiological functions and metabolic regulation in pigs. Imbalances in the ratio of polyunsaturated fatty acids (PUFAs) may influence inflammatory responses, including the modulation of pro-inflammatory cytokines. This study aimed to investigate the gene co-expression profiles in the skeletal muscle of pigs fed diets supplemented with 3.0% soybean, canola, or fish oils, correlating these profiles with cytokine abundance and identifying hub genes associated with immune-related pathways using a systems biology approach. Skeletal muscle samples from 27 pigs were subjected to RNA sequencing and weighted gene co-expression network analysis (WGCNA) to construct gene co-expression networks. The concentrations of six cytokines (IL-10, IFN-γ, IL-1β, IL-6, IL-18, and TNF-α) were quantified in muscle tissue using ELISA. Functional enrichment analysis and hub gene identification revealed several key genes involved in immune function and fatty acid metabolism. WGCNA uncovered distinct co-expression modules associated with specific dietary oil treatments. These findings provide new insights into the immunomodulatory effects of soybean, canola, and fish oils, highlighting the relevance of nutrigenomics in understanding gene-diet interactions in pigs.

PMID:40467700 | DOI:10.1038/s41598-025-04273-0

Trends Plant Sci. 2025 Jun 3:S1360-1385(25)00137-2. doi: 10.1016/j.tplants.2025.05.009. Online ahead of print.

ABSTRACT

Two recent papers provide new insights into plant immunity. Li et al. identified an evolutionary pattern in which reduced pathogen pressure leads to a convergent reduction of immune receptors. While Guo et al. uncovered recurrent losses of nucleotide-binding site-leucine-rich repeat receptors (NLRs), through intergenomic synteny analysis, revealing the molecular mechanism for immune receptor reduction.

PMID:40467438 | DOI:10.1016/j.tplants.2025.05.009

Dent Mater. 2025 Jun 3:S0109-5641(25)00641-4. doi: 10.1016/j.dental.2025.05.006. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the antiproteolytic effect of EGCG-methacrylate monomers and its inhibitory effect on gelatinolytic activity in the hybrid layer. Also, to investigate the effect of an adhesive material functionalized with EGCG-methacrylate monomers on immediate and long-term dentin-resin bond strength.

METHODS: Neat EGCG (E0) was reacted with three different ratios of methacryloyl ester and dissolved in ethyl acetate to obtain EGCG-methacrylates with hydroxyl functionalization at 33 % (M-E33), 67 % (M-E67) and 100 % (M-E100) levels. Resin composite blocks were built on human dentin surfaces using self-etching adhesive containing E0, M-E33, M-E67, and M-E100 at 1 wt%. Demineralized human dentin disks were immersed in deionized water (DW) or lactic acid (LA) and subsequently treated with DW, acetone (as controls), E0, M-E33, M-E67 and M-E100 diluted in acetone. Concentrations of solubilized type I collagen C-terminal (CTX and ICTP) and N-terminal (NTX) telopeptides were determined from 7-day extracts of dentin matrix specimens by ELISA assays. In situ zymography of adhesive-dentin interface slices from restored teeth was performed by confocal microscope after 24 h dentin treatment. Microtensile bond strength (µTBS) and failure pattern were evaluated after 24 h and 6 months. Data were analyzed using two-way ANOVA and Tukey post hoc test (p < 0.05).

RESULTS: All experimental groups statistically reduced the release of solubilized telopeptides from dentin samples in DW and LA. E0 and M-E100 incorporated into the adhesive system reduced the gelatinolytic activity within the hybrid layer. The lowest µTBS values for restored teeth were observed for E0 and M-E100 groups, after 24 h and 6 months, respectively. The most prevalent failure observed was classified as type 4, except for M-E100.

SIGNIFICANCE: EGCG-methacrylate monomers effectively protected collagen from degradation. When incorporated into adhesive systems, EGCG-methacrylates reduced gelatinolytic activity within the hybrid layer, and did not affect immediate and long-term bond strength values of restorations.

PMID:40467428 | DOI:10.1016/j.dental.2025.05.006

Mech Ageing Dev. 2025 Jun 2:112081. doi: 10.1016/j.mad.2025.112081. Online ahead of print.

ABSTRACT

Sex is a key determinant of human phenotype, with males and females exhibiting distinct anthropometric and metabolic features that influence disease susceptibility. This study investigated sex-specific metabolic differences in late middle-aged adults without diagnosed metabolic diseases, both in the fasting state and during an oral glucose tolerance test (OGTT). Using data from the NutriTech project, we analyzed plasma metabolomic responses during the OGTT, along with detailed assessments of body composition and fasting clinical parameters. Females exhibited 28% greater total adipose tissue, mainly subcutaneous, whereas males had more intra-abdominal fat and higher energy expenditure. Females showed elevated fasting levels of fatty acids-particularly very-long-chain fatty acids- leptin, and adiponectin. Males had slightly higher fasting glycemia (~ 5%) and a more pronounced glycemic increase during the OGTT (17%), along with elevated insulin levels. In both fasting and postprandial states, males showed higher circulating levels (p<0.05) of aromatic and branched-chain amino acids (BCAA) and their catabolites. Conversely, females had higher sphingomyelins levels during fasting and throughout the OGTT, and increased postprandial levels of secondary bile acids (p<0.05). These sex-specific metabolic features in late middle-aged adults may enhance our understanding of metabolic disease risk and support the development of more targeted prevention strategies. CLINICAL TRIAL REGISTRATION NUMBER: NCT01684917.

PMID:40467008 | DOI:10.1016/j.mad.2025.112081

Dev Biol. 2025 Jun 2:S0012-1606(25)00145-9. doi: 10.1016/j.ydbio.2025.05.022. Online ahead of print.

ABSTRACT

Vertebrate development from an egg to a complex multi-cell organism is accompanied by multiple phases of genome-scale changes in the repertoire of proteins and their post-translational modifications. While much has been learned at the RNA level, we know less about changes at the protein level. In this paper, we present a deep analysis of changes of ∼15,000 proteins and ∼11,500 phospho-sites at 11 developmental time points in Xenopus laevis embryos ranging from the stage VI oocyte to juvenile tadpole. We find that the most dramatic changes to the proteome occur during the transition to functional organ systems, which occurs as the embryo becomes a tadpole. At that time, the absolute amount of non-yolk protein increases two-fold, and there is a shift in the balance of expression from proteins regulating gene expression to receptors, ligands, and proteins involved in cell-cell and cell-environment interactions. Between the early and late tadpole, the median increase for membrane and secreted proteins is substantially higher than that of nuclear proteins. To begin to appreciate changes at the post-translational level, we have measured quantitative phospho-proteomic data across the same developmental stages. In contrast to the significant protein changes that are concentrated at the end of the time series, the most significant phosphorylation changes are concentrated in the very early stages of development. A clear exception are phosphorylations of proteins involved in gene expression: these increase just after fertilization, with patterns that are highly correlated with the underlying protein changes. To facilitate the interpretation of this unique phospho-proteome data set, we created a pipeline for identifying homologous human phosphorylations from the measured Xenopus phospho-proteome. Collectively, our data reveal multiple coordinated transitions in protein and phosphorylation profiles, reflecting distinct developmental strategies and providing an extensive resource to further explore developmental biology at the proteomic and phospho-proteomic levels.

PMID:40466852 | DOI:10.1016/j.ydbio.2025.05.022

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Jun 2;343:126507. doi: 10.1016/j.saa.2025.126507. Online ahead of print.

ABSTRACT

BACKGROUND: As the number of people with dementia grows, it becomes even more important to improve how it is diagnosed and treated. Metabolomics, the study of small molecule metabolites in biological systems, helps us learn a lot about dementia by revealing changes in the brain's systems through blood plasma research.

OBJECTIVE: The objective of this study is to clarify the changes in metabolism that are linked to dementia. This will be achieved by using metabolic fingerprinting techniques on human plasma to differentiate between patients with dementia and individuals who have normal cognitive function.

METHODS: This study used data from the Birjand Longitudinal Aging Study and high-tech Raman Spectroscopy, as well as multivariate statistical methods such as PCA and OPLS-DA. The study looked at 34 people with dementia and 34 people who did not have any cognitive damage.

RESULTS: Metabolic fingerprints distinguished two groups with extremely distinct metabolic characteristics. Main findings demonstrate that oxidative stress and energy metabolism metabolites have changed significantly. OPLS-DA distinguished healthy and dementia samples with high accuracy and sensitivity. Both the expected high model accuracy and the clear score plot split confirmed this.

CONCLUSION: The metabolic deviations detected offer a deeper understanding of the biochemical processes associated with dementia. These results enhance our understanding of dementia-related biochemical changes and underscore the exploratory potential of Raman-based metabolomic fingerprinting as a complementary, non-invasive approach for identifying broader functional group-level alterations.

PMID:40466487 | DOI:10.1016/j.saa.2025.126507

Talanta. 2025 May 22;296:128326. doi: 10.1016/j.talanta.2025.128326. Online ahead of print.

ABSTRACT

Immunoglobulin G (IgG) subclasses glycosylation reflects the progression of colorectal cancer (CRC). Precise identification of IgG subclass-specific glycopeptides is a critical step. However, it is still hard to achieve a one-step mass spectrometry (MS) since all four subclasses of IgG (IgG1- IgG4) contain several possible N-glycans in the Fc regions with a highly similar amino acid sequence. In this study, we set up a label-free workflow to quantify IgG subclass site-specific N-glycopeptides in a single run MS based on the poly (glycerol methacrylate) @ chitosan (PGMA@CS) nanomaterial enrichment. The nanomaterial was used to purify glycopeptides effectively and the LC-SCE-HCD-MS/MS was used to obtain the peptide and glycan fragment in one single run MS. Through our workflow, all four subtypes of IgG glycopeptides were distinguished. For the first time, a total of 89 biantennary IgG subclass-specific N-glycopeptides were detected for quantification in 50 CRC patients and 66 healthy individuals. We have found that the decrease in galactosylation, fucosylation of sialylated glycans, sialylation of IgG2-Fc was associated with colorectal cancer. The results demonstrated that the glycopeptides of IgG-Fc are associated with CRC and potential to serve as noninvasive biomarkers. And it implies that the workflow can also accommodate the precise high-throughput identification of intact N-glycopeptides at the proteome scale.

PMID:40466447 | DOI:10.1016/j.talanta.2025.128326

PLoS One. 2025 Jun 4;20(6):e0324513. doi: 10.1371/journal.pone.0324513. eCollection 2025.

ABSTRACT

SARS-CoV-2 infection has been associated with increased autoimmune disease risk. Past studies have not aligned regarding the most prevalent autoimmune diseases after infection, however. Furthermore, the relationship between infection severity and new autoimmune disease risk has not been well examined. We used RECOVER's electronic health record (EHR) networks, N3C, PCORnet, and PEDSnet, to estimate types and frequency of autoimmune diseases arising after SARS-CoV-2 infection and assessed how infection severity related to autoimmune disease risk. We identified patients of any age with SARS-CoV-2 infection between April 1, 2020 and April 1, 2021, and assigned them to a World Health Organization COVID-19 severity category for adults or the PEDSnet acute COVID-19 illness severity classification system for children (<age 21). We collected baseline covariates from the EHR in the year pre-index infection date and followed patients for 2 years for new autoimmune disease, defined as ≥ 2 new ICD-9, ICD-10, or SNOMED codes in the same concept set, starting >30 days after SARS-CoV-2 infection index date and occurring ≥1 day apart. We calculated overall and infection severity-stratified incidence ratesper 1000 person-years for all autoimmune diseases. With least severe COVID-19 severity as reference, survival analyses examined incident autoimmune disease risk. The most common new-onset autoimmune diseases in all networks were thyroid disease, psoriasis/psoriatic arthritis, and inflammatory bowel disease. Among adults, inflammatory arthritis was the most common, and Sjögren's disease also had high incidence. Incident type 1 diabetes and hematological autoimmune diseases were specifically found in children. Across networks, after adjustment, patients with highest COVID-19 severity had highest risk for new autoimmune disease vs. those with least severe disease (N3C: adjusted Hazard Ratio, (aHR) 1.47 (95%CI 1.33-1.66); PCORnet aHR 1.14 (95%CI 1.02-1.26); PEDSnet: aHR 3.14 (95%CI 2.42-4.07)]. Overall, severe acute COVID-19 was most strongly associated with autoimmune disease risk in three EHR networks.

PMID:40465573 | DOI:10.1371/journal.pone.0324513

PLoS Comput Biol. 2025 Jun 4;21(6):e1013082. doi: 10.1371/journal.pcbi.1013082. eCollection 2025 Jun.

ABSTRACT

Eastern equine encephalitis virus (EEEV) is an arthropod-borne, positive-sense RNA alphavirus posing a substantial threat to public health. Unlike similar viruses such as SARS-CoV-2, EEEV replicates efficiently in neurons, producing progeny viral particles as soon as 3-4 hours post-infection. EEEV infection, which can cause severe encephalitis with a human mortality rate surpassing 30%, has no licensed, targeted therapies, leaving patients to rely on supportive care. Although the general characteristics of EEEV infection within the host cell are well-studied, it remains unclear how these interactions lead to rapid production of progeny viral particles, limiting development of antiviral therapies. Here, we present a novel rule-based model that describes attachment, entry, uncoating, replication, assembly, and export of both infectious virions and virus-like particles within mammalian cells. Additionally, it quantitatively characterizes host ribosome activity in EEEV replication via a model parameter defining ribosome density on viral RNA. To calibrate the model, we performed experiments to quantify viral RNA, protein, and infectious particle production during acute infection. We used Bayesian inference to calibrate the model, discovering in the process that an additional constraint was required to ensure consistency with previous experimental observations of a high ratio between the amounts of full-length positive-sense viral genome and negative-sense template strand. Overall, the model recapitulates the experimental data and predicts that EEEV rapidly concentrates host ribosomes densely on viral RNA. Dense packing of host ribosomes was determined to be critical to establishing the characteristic positive to negative RNA strand ratio because of its role in governing the kinetics of transcription. Sensitivity analysis identified viral transcription as the critical step for infectious particle production, making it a potential target for future therapeutic development.

PMID:40465541 | DOI:10.1371/journal.pcbi.1013082

Angew Chem Int Ed Engl. 2025 Jun 4:e202507254. doi: 10.1002/anie.202507254. Online ahead of print.

ABSTRACT

Crosslinking strategies have emerged as an attractive technology for deciphering protein complexes and protein-protein interactions (PPIs). However, commonly used crosslinking strategies present significant challenges for the precise analysis of protein complexes and dynamic PPIs in native biological environments. Here, we report the development of the first visible-light-inducible lysine-specific homobifunctional photo-crosslinkers and introduce Visible-light-controlled Lysine-selective crosslinking (VL-XL) strategy for in-depth analysis of protein complexes and profiling dynamic interactomes in live cells. By synergistically integrating the advantages of temporal control, high biocompatibility, and lysine selectivity, the VL-XL strategy not only provides an effective solution for protein complexes studies-achieving residue-specific crosslinked peptides, delivering high-confidence data and streamlined MS data analysis-but also reveals dynamic interactomes in various scenarios. The VL-XL strategy successfully profiles the time-resolved, EGF-stimulated EGFR interactome, providing valuable insights into regulatory mechanisms of EGFR signaling. More importantly, the VL-XL strategy effectively unveils molecular glue degrader-induced E3 ligase interactome, leading to discovery of neo-substrates such as SESN2 and opening an innovative avenue for identifying novel targets for degradation. Overall, the VL-XL strategy offers a robust chemical tool for decoding protein complexes and dynamic interactomes, inspiring innovative solutions to address unresolved questions in proteomics, systems biology and drug discovery.

PMID:40464585 | DOI:10.1002/anie.202507254

Nat Prod Rep. 2025 Jun 4. doi: 10.1039/d5np00002e. Online ahead of print.

ABSTRACT

Covering up to 2025.Plant-derived polyphenols of various chemical classes are widely distributed in dietary substances, e.g. fruits, nuts, vegetables and teas. Such phenolic derivatives are natural antioxidants and have been linked with numerous health benefits, notably anti-cancer and anti-inflammatory properties. Additionally, they may behave as mild estrogens, as in the case of genistein. However, there has often been no clear correlation between in vitro properties, as measured in cell lines for instance, and in vivo performance. Moreover, it is not always clear what the true active species might be, as most phenols are readily subject to phase II metabolism, generating predominantly glucuronides and sulfates. In this highlight, we seek to address the question of whether dietary substance metabolites, especially glucuronides, which have been more widely studied, do indeed possess distinct activities in their own right compared to their parent substances. In most cases this will refer to enzyme inhibition and/or interaction with cell lines. General observations concerning glucuronidation are provided, accompanied by practical comments concerning the synthesis of glucuronides, which are not always available or marketed in useful quantities. The main structural classes of natural polyphenols are introduced, with comments including synthetic details and biological properties for important members of each class.

PMID:40464213 | DOI:10.1039/d5np00002e

Phys Chem Chem Phys. 2025 Jun 4. doi: 10.1039/d5cp01297j. Online ahead of print.

ABSTRACT

Structural biology is witnessing a transformative era with gas-phase techniques such as native mass spectrometry (MS), ion mobility, and single-particle imaging (SPI) emerging as critical tools for studying biomolecular assemblies like protein capsids in their native states. SPI with X-ray free-electron lasers has the potential to allow for capturing atomic-resolution structures of proteins without crystallization. However, determining particle orientation during exposure remains a major challenge, compounded by the heterogeneity of the protein complexes. Gas-phase Förster resonance energy transfer (FRET) offers a promising solution to assess alignment-induced structural perturbations, providing insights into the stability of the tertiary structure under various activation methods. This study employs molecular dynamics (MD) simulations to explore chromophore integration's effect on ubiquitin's structure and alignment properties in vacuum. Ubiquitin serves as an ideal model due to its small size, well-characterized properties, and computational simplicity. By investigating chromophore placement, we identified optimal sites for monitoring gas-phase denaturation and unfolding processes, advancing SPI applications and a broader understanding of protein stability in the gas phase.

PMID:40464121 | DOI:10.1039/d5cp01297j

Front Genet. 2025 May 20;16:1618183. doi: 10.3389/fgene.2025.1618183. eCollection 2025.

NO ABSTRACT

PMID:40463713 | PMC:PMC12129931 | DOI:10.3389/fgene.2025.1618183

Front Immunol. 2025 May 20;16:1588419. doi: 10.3389/fimmu.2025.1588419. eCollection 2025.

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint inflammation and damage, leading to disability and pain. The etiology of RA is undefined but considered multifactorial, as interactions between genetics and environmental factors lead to the generation of autoantibodies that target synovial joints. Smoking is a well-established and widely studied risk factor for RA development and is associated with a reduced response to treatments and poor clinical outcomes. Murine models of inflammatory arthritis have provided many insights into the pathogenesis of RA and have recently been used to explore the relationship between cigarette smoking and RA. In this review, we comprehensively appraise the current literature investigating cigarette smoke exposure in murine models of inflammatory arthritis, focused on RA. The current literature indicates that the influence of smoke exposure on molecular and disease outcomes depends on the timepoint of exposure and genetic background of the mice. Further, dose-dependent increases in disease manifestations reproduce human clinical data that the intensity of smoking is linked to disease but demosntrate that there may be a plateau effect. Finally, we consolidate mechanistic findings to describe a potential mechanism through which cigarette smoke exacerbates murine arthritis. Understanding how these factors, genetics, timing, and intensity of exposure modulate response to CS in inflammatory arthritis models may lead to better drug development and personalized treatment strategies, ultimately improving outcomes for RA patients with a smoking history.

PMID:40463383 | PMC:PMC12129895 | DOI:10.3389/fimmu.2025.1588419

Front Bioeng Biotechnol. 2025 May 20;13:1610782. doi: 10.3389/fbioe.2025.1610782. eCollection 2025.

ABSTRACT

[This corrects the article DOI: 10.3389/fbioe.2024.1500756.].

PMID:40462842 | PMC:PMC12132079 | DOI:10.3389/fbioe.2025.1610782

Development. 2025 Jun 2:dev.204312. doi: 10.1242/dev.204312. Online ahead of print.

ABSTRACT

Long-range morphogen gradients have been proposed to form by morphogen diffusion from a localized source to distributed sinks in the target tissue. The role of the complex tissue geometry in this process is, however, less well understood and has not been explicitly resolved in existing models. Here, we numerically reconstruct pore-scale 3D geometries of zebrafish epiboly from light-sheet microscopy volumes. In these high-resolution 3D geometries, we simulate Fgf8a gradient formation in the tortuous extracellular space. Our simulations show that when realistic embryo geometries are considered, a source-diffusion-degradation mechanism with additional binding to extracellular matrix polymers is sufficient to explain self-organized emergence and robust maintenance of Fgf8a gradients. The predicted normalized gradient is robust against changes in source and sink rates but sensitive to changes in the pore connectivity of the extracellular space, with lower connectivity leading to steeper and shorter gradients. This demonstrates the importance of considering realistic geometries when studying morphogen gradients.

PMID:40462756 | DOI:10.1242/dev.204312

Clin Mol Hepatol. 2025 Jun 4. doi: 10.3350/cmh.2025.0292. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection remains a global health challenge, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Despite the high efficacy of direct-acting antiviral (DAA) therapy in achieving sustained virologic response (SVR), concerns persist regarding long-term immune alterations and residual risks, particularly in cirrhotic patients.

METHODS: This study investigates 75 soluble immune mediator (SIM) profiles in 102 chronic HCV patients, stratified by cirrhosis status, at therapy initiation, end of treatment, and long-term follow-up (median 96 weeks). Findings were compared with 51 matched healthy controls and validated in an independent cohort of 47 cirrhotic patients, 17 of whom developed HCC.

RESULTS: We observed significant SIM alterations at baseline, with cirrhotic patients displaying a more profoundly dysregulated inflammatory milieu. Despite an overall decline in inflammatory markers following SVR, persistent alterations were evident, particularly in cirrhotic patients. Notably, those with liver stiffness exceeding 14 kPa exhibited sustained inflammatory dysregulation, correlating with liver elastography values. Key SIM such as IL-6, IL-8, urokinase plasminogen activator (uPA), and hepatocellular growth factor (HGF) remained elevated and were associated with HCC development. Network analysis highlighted their roles in liver fibrosis, regeneration, and carcinogenesis.

CONCLUSIONS: These findings underscore the importance of early antiviral intervention to prevent cirrhosis-related sequelae. Future studies should explore the mechanistic pathways linking chronic inflammation, fibrosis, and oncogenesis to identify predictive biomarkers and novel therapeutic targets. Addressing persistent immune alterations post-HCV clearance may improve long-term outcomes, particularly in patients with advanced liver disease.

PMID:40462644 | DOI:10.3350/cmh.2025.0292

Nat Commun. 2025 Jun 3;16(1):5151. doi: 10.1038/s41467-025-60234-1.

ABSTRACT

Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids (SLs) that are derived from an iterative type I polyketide synthase (PKS) cluster PfSgaAB, thereby revealing a non-canonical pathway for the production of bacterial SLs as secondary metabolites. SL production is common in eukaryotes but was thought to be limited to a few bacterial phyla that encode the serine palmitoyltransferase (SPT) enzyme, which catalyses the initial step in SL synthesis. We demonstrate that PfSgaB encodes a pyridoxal 5'-phosphate-dependent alpha-oxoamine synthase with SPT activity, and find homologous putative PKS clusters present across host-associated bacteria that are so far unknown SL producers. Moreover, we provide evidence that MYb115-derived SLs affect C. elegans defence against Bt infection by altering SL metabolism in the nematode host. This work establishes SLs as structural outputs of bacterial PKS and highlights the role of microbiota-derived SLs in host protection against pathogens.

PMID:40461452 | DOI:10.1038/s41467-025-60234-1

Bull Math Biol. 2025 Jun 3;87(7):91. doi: 10.1007/s11538-025-01471-9.

ABSTRACT

The concept of control is crucial for effectively understanding and applying biological network models. Key structural features relate to control functions through gene regulation, signaling, or metabolic mechanisms, and computational models need to encode these. Applications often focus on model-based control, such as in biomedicine or metabolic engineering. In a recent paper, the authors developed a theoretical framework of modularity in Boolean networks, which led to a canonical semidirect product decomposition of these systems. In this paper, we present an approach to model-based control that exploits this modular structure, as well as the canalizing features of the regulatory mechanisms. We show how to identify control strategies from the individual modules, and we present a criterion based on canalizing features of the regulatory rules to identify modules that do not contribute to network control and can be excluded. For even moderately sized networks, finding global control inputs is computationally challenging. Our modular approach leads to an efficient approach to solving this problem. We apply it to a published Boolean network model of blood cancer large granular lymphocyte (T-LGL) leukemia to identify a minimal control set that achieves a desired control objective.

PMID:40461704 | DOI:10.1007/s11538-025-01471-9

PLoS One. 2025 Jun 3;20(6):e0322226. doi: 10.1371/journal.pone.0322226. eCollection 2025.

ABSTRACT

Sarcocystis calchasi is a pathogenic apicomplexan parasite affecting avian species of several orders. To complete its heteroxenous life cycle, S. calchasi infects a wide range of avian intermediate hosts and accipitriform raptors serve as definitive hosts. The mechanism of invasion into host cells is largely understood in other apicomplexan parasites, particularly Toxoplasma gondii, which also belongs to the family of Sarcocystidae. However, Sarcocystis species exhibit several distinguishing features in their life cycles and in their secretory organelles. The composition of secretory pathogenesis determinants, including surface antigens and secretory organelle proteins, has been shown to differ between closely related species, as evidenced by Sarcocystis neurona. In this study, whole-genome sequencing was performed on S. calchasi, and transcriptomes were determined by RNA-seq of S. calchasi sporozoites and bradyzoites derived from intermediate and definitive hosts as well as from merozoites propagated in primary embryonal pigeon liver cells. The S. calchasi genome contains homologs of genes encoding proteins associated with the well-conserved host invasion machinery like AMA1 and rhoptry neck proteins, albeit with a markedly reduced number of genes encoding surface antigens, rhoptry and dense granule proteins in comparison to T. gondii. Our transcriptome analysis revealed different gene expression profiles between S. calchasi sporozoites, merozoites and bradyzoites. Factors associated with host cell attachment (surface antigens and micronemal proteins) were expressed predominantly either in sporozoites and merozoites or in bradyzoites. As sporozoites and merozoites invade various intermediate hosts and cell types whereas bradyzoites enter definitive host intestinal epithelium, their differential expression patterns indicate that S. calchasi utilizes different sets of secretory pathogenesis determinants for host cell attachment and invasion, depending on the type of host and cell.

PMID:40460112 | DOI:10.1371/journal.pone.0322226