Plant J. 2025 Jul;123(2):e70377. doi: 10.1111/tpj.70377.

ABSTRACT

Grain weight is one of the critical determinants of wheat (Triticum aestivum L.) yield, and understanding its genetic and molecular mechanisms is essential for improving crop productivity. Here, we find that TaSG-D1, which encodes an STKc-GSK3 kinase, negatively regulates grain weight. TaSG-D1 interacts with and phosphorylates TaGAMyb to reduce its degradation. Overexpression of TaGAMyb results in decreased grain length and weight, whereas its knockout increases both agronomic traits in wheat. Further investigation reveals that TaGAMyb directly activates the expression of TaCKX2.2.1, a negative regulator of grain development. Transcriptome profiling shows differential expression of TaCKX2.2.1 in 15-DAP grain of WT and TaGAMyb knockout lines, ultimately leading to a decreased concentration of active cytokinin in grains. Taken together, our findings demonstrate that TaSG-D1 negatively regulates grain development by increasing the protein abundance of transcription factor TaGAMyb, which in turn promotes the expression of downstream gene TaCKX2.2.1, a key regulator of cytokinin signaling.

PMID:40720714 | DOI:10.1111/tpj.70377

PLoS One. 2025 Jul 28;20(7):e0329115. doi: 10.1371/journal.pone.0329115. eCollection 2025.

ABSTRACT

In marine ecosystems, microbial communities often interact using specialised metabolites, which play a central role in shaping the dynamics of the ecological networks and maintaining the balance of the ecosystem. With metabolomics and transcriptomics analyses, this study explores the interactions between two marine microalgae, Skeletonema marinoi and Prymnesium parvum, grown in mono-cultures and non-contact co-cultures. As a growth indicator, the photosynthetic potential, measured via fluorescence, suggested chemical interaction between S. marinoi and P. parvum. Using Liquid Chromatography-Mass Spectrometry (LC-MS) data, we identified 346 and 521 differentially produced features in the endo- and exometabolome of S. marinoi and P. parvum, respectively. Despite limited tandem mass spectrometry data (MS2) for these features, we structurally annotated 14 compounds, most of which were previously under-studied specialised metabolites. Differential gene expression analysis was then performed on the transcriptomes of the microalgae, which uncovered differentially expressed genes involved in energy metabolism and cellular repair for both species. These metabolic changes depict the adaptation of both species in the co-culture. However, further data acquisition and investigation will be necessary to confirm the type of interaction and the underlying mechanisms.

PMID:40720431 | DOI:10.1371/journal.pone.0329115

Elife. 2025 Jul 28;13:RP93906. doi: 10.7554/eLife.93906.

ABSTRACT

Genotype-phenotype mapping (GPM), or the association of trait variation to genetic variation, has been a long-lasting problem in biology. The existing approaches to this problem allowed researchers to partially understand within- and between-species variation as well as the emergence or evolution of phenotypes. However, traditional GPM methods typically ignore the transcriptome or have low statistical power due to challenges related to dataset scale. Thus, it is not clear to what extent selection modulates transcriptomes and whether cis- or trans-regulatory elements are more important. To overcome these challenges, we leveraged the cost efficiency and scalability of single-cell RNA sequencing (scRNA-seq) by collecting data from 18,233 yeast cells from 4489 F2 segregants derived from an F1 cross between the laboratory strain BY4741 and the vineyard strain RM11-1a. More precisely, we performed expression quantitative trait loci (eQTL) mapping with the scRNA-seq data to identify single-cell eQTL and transcriptome variation patterns associated with fitness variation inferred from the segregant bulk fitness assay. Due to the larger scale of our dataset and its multidimensionality, we could recapitulate results from decades of work in GPM from yeast bulk assays while revealing new associations between phenotypic and transcriptomic variations at a broad scale. We evaluated the strength of the association between phenotype variation and expression variation, revealed new hotspots of gene expression regulation associated with trait variation, revealed new gene functions with high expression heritability, and highlighted the larger aggregate effect of trans-regulation compared to cis-regulation. Altogether, these results suggest that integrating large-scale scRNA-seq data into GPM improves our understanding of trait variation in the context of transcriptomic regulation.

PMID:40720279 | DOI:10.7554/eLife.93906

Cell Rep. 2025 Jul 26;44(8):116060. doi: 10.1016/j.celrep.2025.116060. Online ahead of print.

ABSTRACT

Adipose tissue remodels via hypertrophy or hyperplasia in response to nutrient status, but the mechanisms governing these expansion modes remain unclear. Here, we identify a nutrient-sensitive epigenetic circuit linking glucose metabolism to chromatin remodeling during adipogenesis. Upon glucose stimulation, α-ketoglutarate (α-KG) accumulates in the nucleus and activates the histone demethylase JMJD1A to remove repressive histone H3 lysine 9 dimethylation (H3K9me2) marks at glycolytic and adipogenic gene loci, including Pparg. JMJD1A is recruited to pre-marked promoter chromatin via nuclear factor IC (NFIC), enabling carbohydrate-responsive element-binding protein (ChREBP) binding and transcriptional activation. This feedforward mechanism couples nutrient flux to chromatin accessibility and gene expression. In vivo, JMJD1A is essential for de novo adipogenesis and hyperplastic expansion in visceral fat under nutrient excess. JMJD1A deficiency impairs hyperplasia, exacerbates adipocyte hypertrophy, and induces local inflammation. These findings define a glucose-α-KG-JMJD1A-ChREBP axis regulating depot-specific adipogenesis and uncover a chromatin-based mechanism by which glucose metabolism governs adaptive adipose tissue remodeling.

PMID:40720241 | DOI:10.1016/j.celrep.2025.116060

Curr Microbiol. 2025 Jul 28;82(9):414. doi: 10.1007/s00284-025-04402-y.

ABSTRACT

Escherichia coli is widely used as an indicator of faecal contamination, as it is assumed that faeces from warm-blooded animals is the primary source of E. coli in the environment. However, various studies have shown that E. coli can survive and multiply in environmental niches, including soil, sand and sediment. E. coli can be assigned to eight main phylogroups but environmental E. coli are associated primarily with phylogroups A and B1. In this study, 410 E. coli were isolated from different niches within two peri-urban catchments in the Gauteng province of South Africa. To represent the E. coli circulating within the human population, E. coli was also isolated from sewage before treatment and released into these reservoirs. To capture the diversity of E. coli among these isolates, the β-D-glucuronidase (uidA) and mismatch repair (mutS) genes were sequenced. While isolates linked to phylogroup B1 dominated as was expected, the recovery of many isolates linked to phylogroup B2, the second most dominant group, was unanticipated. To further investigate this observation, the genomes of representative phylogroup B2 isolates were sequenced and subjected to phylogenetic and functional analyses. The results showed that phylogroup B2 isolates formed a distinct phylogenetic cluster, apparently independent of niche or geographic origin. Our findings also showed that while isolates seem to be associated with environmental samples, they could have the ability to colonize the gut and cause disease as they harboured several virulence factors associated with extraintestinal E. coli.

PMID:40719781 | DOI:10.1007/s00284-025-04402-y

Biochem Soc Trans. 2025 Jul 28:BST20253035. doi: 10.1042/BST20253035. Online ahead of print.

ABSTRACT

The endoplasmic reticulum (ER) is a vital organelle involved in the biogenesis of membrane and secreted proteins. Proteostasis (protein homeostasis) in the ER relies on finely co-ordinated mechanisms for translocation of polypeptides from the cytosol to the organelle lumen and membrane, introduction of co- and post-translational modifications, protein folding and quality control, exportation of mature proteins and disposal of unfolded or aggregated species, besides the regulation of gene expression to adjust the proteostasis network to the cellular demands for protein biogenesis. Neurodevelopmental processes involving neurogenesis, neuronal migration and differentiation, neural circuit wiring, synaptogenesis, among others, require extensive proteome diversification and remodeling, with high fluxes through the secretory pathways constantly challenging ER proteostasis. Genetic defects affecting the different nodes of the ER proteostasis network can severely disturb neurodevelopment. Here, we compile evidence illustrating how perturbations to the different steps of protein biogenesis in the ER can lead to neurological disorders and present major questions to guide research in the field.

PMID:40719631 | DOI:10.1042/BST20253035

Nano Lett. 2025 Jul 28. doi: 10.1021/acs.nanolett.5c02506. Online ahead of print.

ABSTRACT

The rational construction of three-dimensional (3D) crystalline lattices from synthetic short-chain polymers remains a significant challenge due to the lack of inherent driving forces to enable crystal growth in all three dimensions. Here, we report the design of 3D peptoid crystals from linear peptoid hexamers, derived from amphiphilic diblock sequences that typically form crystalline two-dimensional (2D) nanosheets. By removing the amorphous domains and tuning the chain termini, crystalline lamellae up to 500 nm thick were achieved, far exceeding the thickness of typical nanosheets (on the order of a few nanometers). These 3D crystals form via the stacking of unit cells with lattice parameters similar to those in 2D nanosheets, where terminal groups, particularly compact C-terminal moieties, facilitate vertical growth and enhance crystallinity. This study highlights the importance of atomic precision in terminus chemistry for achieving long-range ordering and isotropic crystal growth in the design of macroscale crystals from oligomeric peptoids.

PMID:40719458 | DOI:10.1021/acs.nanolett.5c02506

Biodivers Data J. 2025 Jul 17;13:e158080. doi: 10.3897/BDJ.13.e158080. eCollection 2025.

ABSTRACT

BACKGROUND: The majority of members of the fungal genus Dermoloma have been described, based on morphology and without molecular support. Sequencing most Dermoloma type specimens has been unsuccessful, probably due to degraded DNA, leaving their taxonomy primarily reliant on morphological characters. In this study, we re-described nine Dermoloma types, providing standardised morphological descriptions that include observations of previously undocumented microscopic structures.

NEW INFORMATION: The pileipellis structure of D.hybridum, D.inconspicuum and D.intermediumvar.coniferarum differs strongly from the typical Dermoloma pileipellis and these taxa do not belong to this genus. Dermolomaatrobrunneum and D.hymenocephalum are distinct taxa which have not been reported recently. The concept of Dermolomacuneifoliumvar.punctipes is based on the presence of dark spots on the stipe. However, our examination of the type material reveals that its spores are more consistent with those of D.atrocinereum, a species that can also exhibit dark dots. Dermolomalongibasidiatum is likely a synonym of this species as well. The name D.pseudocuneifolium has been misapplied for a species with amyloid spores, but the type has inamyloid narrow spores characteristic for D.bellerianum. Dermolomapragense probably represents a distinct, but recently unrecorded European species defined by large basidiomata and small spores. The data presented here are essential for future nomenclatural treatments within Dermoloma, as current phylogenetic studies suggest the presence of a large number of undescribed species.

PMID:40718846 | PMC:PMC12290463 | DOI:10.3897/BDJ.13.e158080

Front Mol Biosci. 2025 Jul 11;12:1632027. doi: 10.3389/fmolb.2025.1632027. eCollection 2025.

ABSTRACT

BACKGROUND: Uveitis is a complex intraocular inflammatory disease and pathology results from the continuous production of proinflammatory cytokines in the optical axis. Qinghuo Rougan Formula (QHRGF), a traditional Chinese medicine (TCM) is now used to treat uveitis with desirable effect. However, the mechanism of action is still unclear. This study aimed to explore the potential diagnostic and therapeutic biomarkers for uveitis using systems biology methods, including network pharmacology and weighted gene co-expression network analysis (WGCNA).

METHODS: A molecular drug-compound-target-uveitis interaction network was established using network pharmacology. Functional enrichment analyses were performed to screen potential signaling pathways. The uveitis gene expression dataset from the Gene Expression Omnibus database was subjected to WGCNA to identify gene co-expression modules related to uveitis and explore the potential hub genes. The least absolute shrinkage and selection operator (LASSO) model was used to identify the hub genes. Additionally, molecular docking was performed to verify the accuracy and stability of the model. Finally, the suppressive effects of QHRGF on uveitis were experimentally verified in vivo.

RESULTS: Network pharmacology and functional enrichment analysis showed that 18 targets and immune/inflammation-related pathways were associated with the QHRGF-targeted pathway network. The yellow module contained 120 genes had a strong correlation with uveitis using WGCNA. In total, 12 putative targets of QHRGF, differentially expressed genes, and yellow module genes were determined. Six hub genes were identified using LASSO model and the receiving operating characteristic curve analysis demonstrated the model can serve as biomarkers for uveitis. The advantages of these genes were approved using molecular docking. Finally, in vivo experiments provided evidence confirming that QHRGF was identified as the key target of the anti-inflammatory effect of uveitis.

CONCLUSION: In conclusion, this research revealed that QHRGF can be used to treat uveitis through multiple components and targets. Meanwhile, the potential anti-inflammatory action of QHRGF in the treatment of uveitis was verified by combining network pharmacology and in vivo experiments, suggesting its potential as a quite prospective agent for the therapy of uveitis.

PMID:40718791 | PMC:PMC12289509 | DOI:10.3389/fmolb.2025.1632027

Iran J Pharm Res. 2025 Feb 22;24(1):e151574. doi: 10.5812/ijpr-151574. eCollection 2025 Jan-Dec.

ABSTRACT

BACKGROUND: One of the most promising strategies to combat cancer is the use of immunotoxins.

OBJECTIVES: This study aimed to design two immunotoxins composed of antibody fragments against the EphA2 receptor, which is highly expressed in breast cancer.

METHODS: EphA2-N-ricin and EphA2-C-ricin were designed by fusing scFv against the EphA2 receptor with the A chain of ricin in varying orders. mFold was used to analyze the mRNA stability of the constructs. The 2D and 3D protein structures of the constructs were predicted using prediction tools and verified by quality assessment tools. The physicochemical properties were calculated using ProtParam. Docking between the constructs and the EphA2 receptor was performed using HADDOCK software, and the 2D interaction plots of the complexes were generated using LigPlus. A 100 ns molecular dynamics (MD) simulation was conducted for docked complexes using Gromacs. Ultimately, the allergenicity and antigenicity of the constructs were determined.

RESULTS: The designed immunotoxins had stable mRNAs, reliable 2D and 3D protein structures, and demonstrated high affinity and stable interactions with the receptor protein, as revealed by docking and MD analyses. Higher binding affinity and stability were observed for construct 2. Moreover, the designed immunotoxins lacked allergenicity and were identified as antigens.

CONCLUSIONS: Based on these observations, it is reasonable to conclude that both designed immunotoxins could serve as suitable immunotoxins; however, construct 2 exhibits more promising properties. Given these results, these immunotoxins could be used in empirical studies to treat breast cancer in vitro or in vivo.

PMID:40718433 | PMC:PMC12296653 | DOI:10.5812/ijpr-151574

iScience. 2025 Jul 3;28(8):113046. doi: 10.1016/j.isci.2025.113046. eCollection 2025 Aug 15.

ABSTRACT

Hemozoin (HZ), the malaria pigment, is associated with the disease when released during the pro-inflammatory blood stage and co-infections with bacteria lead to a more severe disease progression. The underlying mechanisms are poorly understood and, here, we show that the impact of co-exposure to HZ and lipopolysaccharide (LPS) on monocyte-derived dendritic cells (moDC) alters the early transcriptional response to a subset of IFNγ controlled genes, HLA-DR, and PD-L1. HZ-exposure had no effect on inflammatory genes, which were substantially induced by LPS. The reduced expression of HLA-DR and PD-L1 by HZ was associated with the chromatin remodeling complex NuRD and a decreased binding of the NF-κB transcription factor RELA compared to cells stimulated with LPS alone. NuRD replaced the SWI/SNF complex variant PBAF at the specific promoters, without chromatin accessibility changes. The immune modulatory effect of HZ may lead to changed immune responses to bacterial co-infections.

PMID:40717771 | PMC:PMC12296537 | DOI:10.1016/j.isci.2025.113046

Immunotargets Ther. 2025 Jul 23;14:787-798. doi: 10.2147/ITT.S491464. eCollection 2025.

ABSTRACT

INTRODUCTION: Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.

METHODS: Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to evaluate the clinical relevance of the signature.

RESULTS: The study uncovered a robust association between high HMS and poor overall survival in HCC patients across multiple independent cohorts. Notably, high HMS patients in IMbrave150 did not show significant benefit of the atezolizumab-bevacizumab treatment in terms of overall survival or progression-free survival compared to sorafenib monotherapy. Conversely, low HMS patients demonstrated superior overall and progression-free survival outcomes with the combination regimen relative to sorafenib alone. Furthermore, an association between high HMS and features of hepatic stem cells and increased genomic instability was identified.

CONCLUSION: This study provides compelling evidence that the HMS could be a predictive biomarker to identify potential HCC patients with therapeutic benefits from combination immunotherapy with atezolizumab and bevacizumab. Leveraging such predictive metabolic biomarkers may pave the way for tailored, precision medicine strategies that maximize therapeutic responses and improve outcomes for HCC patients.

PMID:40717708 | PMC:PMC12296714 | DOI:10.2147/ITT.S491464

J Lipid Res. 2025 Jul 25:100868. doi: 10.1016/j.jlr.2025.100868. Online ahead of print.

ABSTRACT

The mammalian brain is the most cholesterol-rich organ of the body, relying on in situ de novo cholesterol synthesis. Maintaining cholesterol homeostasis is crucial for normal brain function. Oxysterol-binding protein (OSBP)-related proteins (ORPs) are highly conserved cytosolic proteins that coordinate lipid homeostasis by regulating cell signaling, inter-organelle membrane contact sites, and non-vesicular transport of cholesterol. Here, we show that ORP6 is highly enriched in the mammalian brain, particularly within neurons and astrocytes, with widespread expression across distinct brain regions, including the hippocampus, which is essential for learning and memory. Whole-body ablation of ORP6 (Osbpl6-/-) in mice resulted in dysregulation of systemic and brain lipid homeostasis, with elevated levels of brain desmosterol and amyloid-beta oligomers (AβOs). Mechanistically, ORP6 knockdown in astrocytes altered the expression of cholesterol metabolism genes, promoting the accumulation of esterified cholesterol in lipid droplets, reducing cholesterol efflux and plasma membrane cholesterol content, and increasing amyloid-beta precursor protein (APP) processing. Our findings underscore the role of ORP6 in systemic and brain lipid homeostasis, highlighting its importance in maintaining overall brain health.

PMID:40716750 | DOI:10.1016/j.jlr.2025.100868

Eur J Pharmacol. 2025 Jul 25:177992. doi: 10.1016/j.ejphar.2025.177992. Online ahead of print.

ABSTRACT

BACKGROUND: the repurposing of non-steroidal anti-inflammatory drugs like ketoprofen (KET) has shown significant potential in melanoma treatment, with previously demonstrated anticancer properties. However, KET's low water solubility hinders its formulation at high concentrations.

OBJECTIVE: to overcome this challenge, KET-loaded oil-in-water nanoemulsions were developed and optimized, for the topical treatment of melanoma.

METHODS: formulations containing hydrophobic surfactants Capryol® 90, Lauroglycol™ 90, or Plurol® Diisostearique, hydrophilic surfactant Tween® 80, and cosurfactant/cosolvent Transcutol® were developed using spontaneous emulsification, and characterized in what concerned droplet size, polydispersity index (PDI), zeta potential, pH, stability, in vitro drug release, ex vivo drug permeation, and in vitro therapeutic efficacy and safety assessment.

KEY RESULTS: optimized formulations achieved a high drug loading, small (139.1 - 170.5 nm) and reasonably homogeneous (PDI 0.240 - 0.292) droplet sizes, neutral zeta potential (-6.38 to - 9.40 mV), and a skin compatible pH (around 4). Additionally, a controlled and high cumulative in vitro drug release was achieved for selected compositions, with biphasic characteristics (initial burst release followed by a more sustained release), as well as effective ex vivo skin permeation and retention, and good real-time stability. Optimized nanoemulsions significantly reduced B16.F10 murine melanoma cell viability in in vitro cytotoxicity assays, having an enhanced effect when compared to the free drug.

CONCLUSION: therefore, novel KET-loaded nanoemulsions were successfully developed, combining drug repurposing and a relevant scalability potential. Future research should explore these nanoplatforms' potential in in vivo models, investigating the possible synergy when combined with UVA radiation.

PMID:40716630 | DOI:10.1016/j.ejphar.2025.177992

Am J Clin Nutr. 2025 Jul 25:S0002-9165(25)00433-2. doi: 10.1016/j.ajcnut.2025.07.017. Online ahead of print.

ABSTRACT

BACKGROUND: Bile acids (BA), synthesized in the liver as primary BAs (PBAs) and converted by gut microbiota into secondary BAs (SBAs), are implicated in renal health. Diet could influence gut microbiome and BA levels.

OBJECTIVES: We aimed to prospectively investigate the associations of circulating BA and their receptor polymorphisms (e.g., nuclear farnesoid X receptor [FXR]) with chronic kidney disease (CKD) risk in individuals with T2D.

METHODS: This study included 729 participants with newly diagnosed T2D without prevalent CKD from the Dongfeng-Tongji Cohort study in China. Circulating levels of BA subtypes, including PBAs and SBAs in both unconjugated and conjugated forms, were measured via liquid chromatography-tandem mass spectrometry.

RESULTS: During the 5-year follow-up, 113 incident cases of CKD were documented. Higher levels of most PBA species and total unconjugated SBAs were significantly associated with higher risks of incident CKD. The ORs (95% CIs) of CKD comparing the highest to lowest tertile were 2.54 (1.47, 4.39) for chenodeoxycholate (CDCA), 3.04 (1.69, 5.47) for glycocholate (GCA), 2.78 (1.58, 4.88) for glycochenodeoxycholate (GCDCA), 2.12 (1.23, 3.63) for taurochenodeoxycholate (TCDCA), 2.63 (1.52, 4.54) for total unconjugated PBAs, 2.48 (1.40, 4.39) for total conjugated PBAs, and 2.17 (1.27, 3.71) for total unconjugated SBAs (all Ptrend<0.05). Restricted cubic spline analysis showed linear relationships between CDCA, GCA, GCDCA, TCDCA, and total unconjugated PBAs, conjugated PBAs, and unconjugated SBAs and risk of CKD. Additionally, three single nucleotide polymorphisms (SNPs) in FXR (rs2025801, rs56163822, and rs17030295) were significantly associated with CKD risk; and significant multiplicative interactions were found between these SNPs and unconjugated SBAs.

CONCLUSION: Among adults with T2D, higher concentrations of most circulating PBAs and total unconjugated SBAs were linearly associated with higher a risk of CKD, and genetic variations in FXR modified the association of unconjugated SBAs with CKD.

PMID:40716521 | DOI:10.1016/j.ajcnut.2025.07.017

J Environ Manage. 2025 Jul 26;392:126694. doi: 10.1016/j.jenvman.2025.126694. Online ahead of print.

ABSTRACT

Urbanization with a rapid expansion of the road network disrupts ecological processes, fragmenting the landscape, and reducing biodiversity. The frequent machine and human activities involved in road construction led to significant pressure on ecosystems. However, research on the impact of roading building processes in different stages remains lacking information. We performed a bird census for a new highway construction, the SE-40 ring road in Seville, with three-stages: a) active works, b) suspended works stage surrounding, and c) control stage in a natural condition. We analyzed similarities in community composition and bioindicators using the Indicator Value (IndVal) analysis between different stages. Additionally, we calculated several avian biodiversity metrics, including bird species richness, abundance, biodiversity, and diet-specialist species richness (DSR) and abundance (TAB). Road construction significantly impacted species composition (NMDS, ANOSIM p < 0.001, R2 = 0.1692); both active (P. adjusted = 0.006) and suspended work (P. adjusted = 0.009) stages display differences compared to the control group. The number of species and bioindicator increases, but diet-specialist species decreased, from active works (bioindicator = 3; mean TAB = 6; mean DSR = 19) to control group (4; 4.89; 12.61) to suspended works (5; 5.67; 14.89), reflecting a higher homogeneity during the active works with lowest biodiversity (mean Shannon = 2.69 and Simpson = 0.92). Our findings highlight the overlooked value of suspended works as provisional habitats for bird assemblages, suggesting that areas with intensive human activity need specific biodiversity monitoring and implications for conservation efforts. Rigorous specific biodiversity monitoring is essential to mitigate long-term impacts and inform adaptive road planning strategies.

PMID:40716370 | DOI:10.1016/j.jenvman.2025.126694

Vaccine. 2025 Jul 26;62:127504. doi: 10.1016/j.vaccine.2025.127504. Online ahead of print.

ABSTRACT

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g., transcriptomics, proteomics, metabolomics) through a global consortium of clinical networks, leading immunology, pharmacogenomics teams to uncover the molecular mechanisms behind AEFIs. The network ensures accurate and standardized data collection and analysis through rigorous data management and quality assurance processes. INSIS also implements harmonized case definitions and protocols for collecting data and samples related to rare AEFIs, such as myocarditis, pericarditis, and Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) after COVID-19 vaccinations. This protocol outlines the comprehensive approach to enhance risk-benefit assessments of vaccines across populations, identify actionable biomarkers to inform discovery and development of safe vaccines, and support personalized vaccination strategies.

PMID:40716144 | DOI:10.1016/j.vaccine.2025.127504

New Phytol. 2025 Jul 26. doi: 10.1111/nph.70396. Online ahead of print.

ABSTRACT

Stomatal abundance decrease in Arabidopsis triggered by warm temperature is attributed to PIF4-mediated repression of SPEECHLESS (SPCH) expression. We identified the unknown developmental and transcriptional basis of this adaptive response. We traced stomatal lineages in vivo using cell-identity marker lines and mutants, quantified epidermal traits, and conducted RNA sequencing under oscillating temperatures. Prolonged warm temperature or PIF4-overexpression altered cell fates, inducing diverted stomatal precursors (DPs) that lacked stomatal fate, contributing to stomata reduction. DPs originated from meristemoids that lost SPCH expression, lacked MUTE expression, and exited the cell cycle. Short warm-temperature pulses allowed later recovery of SPCH expression and did not induce DPs or stomata reduction. Comparison of transcriptomes obtained during warm-temperature pulses with stomatal lineage cell-specific profiles identified gene expression changes and contrasted their reversibility. Though at warm temperatures, key stomatal drivers were downregulated, most lineages formed stomata through partly modified transcriptional landscapes that promoted uncommitted cell identities and could include noncanonical pathways. Expression changes in stomatal regulators and cell-fate changes explain lineage progression under fluctuating temperatures. Since short-term temperature oscillations prevail in natural conditions, the requirement of long warm-temperature exposure to trigger DPs would prevent stomata reduction by occasional temperature rises. Promoting uncommitted lineage stages provides flexibility to stomatal development under environmental changes.

PMID:40716027 | DOI:10.1111/nph.70396

Mol Ecol. 2025 Jul 26:e70058. doi: 10.1111/mec.70058. Online ahead of print.

ABSTRACT

Parasite infections affect males and females differently across a wide range of species, often due to differences in immune responses. Generally, females tend to have stronger immune defences and lower parasite loads than males. The major histocompatibility complex (MHC) plays a crucial role in the adaptive immune response, and extensive research has explored how variation in this region influences infection and fitness outcomes. However, studies of sex-specific relationships between MHC variation and infection are scarce, perhaps because MHC genes are located on the autosomes, which are shared by both sexes. Here, we provide evidence of sexually antagonistic selection in a wild, group-living mammal-the banded mongoose. Using genetic and life history data collected from over 300 individuals across 25 years, we found that both MHC class I (MHC-I) and MHC class II (MHC-II) diversity influence lifetime reproductive success differently in males and females. Specifically, higher MHC diversity is linked to increased fitness in males but decreased fitness in females. Furthermore, MHC diversity did not differ between the sexes, indicating an unresolved genetic sexual conflict. Our findings demonstrate that sexually antagonistic selection acts on the MHC and may operate across both MHC classes but differently. This study contributes to the growing body of evidence that sex is a significant factor in shaping host immunity and fitness.

PMID:40715789 | DOI:10.1111/mec.70058

Nat Ecol Evol. 2025 Jul 25. doi: 10.1038/s41559-025-02777-6. Online ahead of print.

ABSTRACT

Mutations are more likely to produce some phenotypes than others, but the causal role of these production propensities in the evolution of phenotypic diversity remains unclear. There are two major challenges: it is difficult to separate the effect of the genotype-phenotype (GP) map from that of natural selection when analysing natural diversity, and most extant phenotypes evolved long ago in species whose GP maps cannot be recovered. Here, using two reconstructed ancestral transcription factors that are closely related but differ in function, we created libraries containing all possible amino acid combinations at historically variable sites in the proteins' DNA binding interface (the genotypes) and measured their capacity to specifically bind DNA elements containing all possible combinations of nucleotides at historically variable sites (the phenotypes). The ancestral GP maps were strongly anisotropic (the distribution of phenotypes encoded by genotypes is highly non-uniform) and heterogeneous (the phenotypes accessible around each genotype vary greatly among genotypes), but the extent and direction of these properties differed substantially between the maps. In both cases, these properties steered evolution towards the lineage-specific phenotypes that evolved during history. Our findings establish that ancient properties of the GP relationship were causal factors in the evolutionary process that produced present-day patterns of functional conservation and diversity.

PMID:40715711 | DOI:10.1038/s41559-025-02777-6