Adv Sci (Weinh). 2025 May 14:e2500290. doi: 10.1002/advs.202500290. Online ahead of print.

ABSTRACT

Enhancing the oil or protein content of soybean, a major crop for oil and protein production is highly desirable. GmSWEET10a encodes a sugar transporter that is strongly selected during domestication and breeding, increasing seed size and oil content. GmSWEET10b is functionally similar to GmSWEET10a, yet has not been artificially selected. Here, AlphaFold is used to find that C-terminal variants of GmSWEET10a can endow enhanced or reduced transport activity. Guided by AlphaFold, the functionality is improved for GmSWEET10a in terms of oil content through gene editing. Furthermore, novel GmSWEET10b haplotypes possessing strengthened or weakened sugar-transport capabilities that are absent in nature are engineered. Consequently, soybean oil content or protein content in independent GmSWEET10b gene-edited lines during multi-year and multi-site field trials is consistently increased, without negatively affecting yield. The study demonstrates that the combination of AlphaFold-guided protein design and gene editing has the potential to generate novel beneficial alleles, which can optimize protein function in the context of crop breeding.

PMID:40365797 | DOI:10.1002/advs.202500290

Anal Cell Pathol (Amst). 2025 May 6;2025:1931921. doi: 10.1155/ancp/1931921. eCollection 2025.

ABSTRACT

Introduction: Expression of P16ink4A and FOXP3 is correlated with the grades of cervical lesions. In this study, we determined the diagnostic accuracy of serum P16ink4A and FOXP3 concentrations for detection of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) in a rural setting in Southwestern Uganda. Material and Methods: CIN and CC cases (93 each before treatment), and 93 controls were identified. Clinical and demographic data were documented before quantifying serum P16ink4A and FOXP3 concentrations using quantitative ELISA kits. Cases were confirmed by cytology and/or histology. We employed descriptive statistics, cross-tabulation, and receiver operating curves (ROC) using statistical software for data science (STATA) 17. p-values <0.05 were considered statistically significant. Results: Serum FOXP3 concentration of 0.0545 ng/mL < showed moderate sensitivity (32.22% and 57.78%) for detection of CIN and CC from healthy controls, respectively. It also showed a moderately high specificity of 68.89% for detection of both CIN and CC from healthy controls (AUC-0.6014 and 0.7679, respectively). Serum P16ink4A concentration of 0.946 ng/mL < showed moderate sensitivities (50.00% and 60.00%) and specificities (56.67% and 55.56%) for the detection of CIN and CC from healthy controls, respectively (AUC-0.6085 and 0.7592, respectively). A combination of elevated serum FOXP3 and P16ink4A showed very low sensitivities of 18.89% in detecting CIN from healthy controls and 33.33% for detecting CC from healthy controls. This combination showed high specificity of 83.33% in detecting both CIN and CC from healthy controls (AUC-0.5992 and 0.7642, respectively). Conclusion: Although serum P16ink4A and FOXP3 concentrations showed moderate accuracy, their combination was more specific than sensitive. This combination has a high potential to be applied for diagnosis rather than screening for cervical lesions, at least in the Ugandan population. Combinations of P16ink4A and FOXP3 with other biomarkers could improve diagnostic accuracies. Additionally, studies could be conducted to assess the performance of these biomarkers in the detection of cervical lesions in specific populations, say Human Immunodeficiency Virus (HIV)-positive and HIV-negative populations.

PMID:40365511 | PMC:PMC12074841 | DOI:10.1155/ancp/1931921

PNAS Nexus. 2025 May 13;4(5):pgaf127. doi: 10.1093/pnasnexus/pgaf127. eCollection 2025 May.

ABSTRACT

Due to the ever-increasing wirelessly transmitted data, the development of new transmission standards and higher frequencies in the 5G band is required. Despite basic biophysical considerations that argue against health effects, there is public concern about this technology. Because the skin penetration depth at these frequencies is only 1 mm or less, we exposed fibroblasts and keratinocytes to electromagnetic fields up to ten times the permissible limits, for 2 and 48 h in a fully blinded experimental design. Sham-exposed cells served as negative, and UV-exposed cells as positive controls. Differences in gene expression and methylation due to exposure were small and not higher than expected by chance. These data strongly support the assessment that there is no evidence for exposure-induced damage to human skin cells.

PMID:40365161 | PMC:PMC12070386 | DOI:10.1093/pnasnexus/pgaf127

Plants (Basel). 2025 Apr 23;14(9):1286. doi: 10.3390/plants14091286.

ABSTRACT

Female gametophyte development in flowering plants is a highly intricate process involving a series of tightly regulated biological events, including the establishment and differentiation of a macrospore mother cell (MMC), the formation of a functional macrospore (FM), and the subsequent development of the embryo sac. The seamless progression of these events is crucial for the completion of sexual reproduction and the alternation of generations in plants. Small RNAs are ubiquitously present in eukaryotic organisms. Based on their biogenesis, function, and involvement in biological pathways, plant small RNAs are primarily categorized into four classes: miRNAs (microRNAs), ta-siRNAs (trans-acting-siRNAs), hc-siRNAs (heterochromatic-siRNAs), and nat-siRNAs (natural antisense transcript-derived siRNAs). Current studies show that small RNAs play an important role in plant reproductive development, such as female gametophyte development and ovule development. In this review, we systematically elucidate the biogenesis and molecular mechanism of small RNAs and summarize the latest research advances on their roles in regulating megasporogenesis and megagametogenesis in plants. The aim of this review is to provide insights into the mechanisms underlying plant reproductive development through the lens of small RNAs, offering a theoretical foundation for improving crop quality, yield, genetic improvement, and breeding.

PMID:40364315 | DOI:10.3390/plants14091286

Nutrients. 2025 Apr 23;17(9):1408. doi: 10.3390/nu17091408.

ABSTRACT

Background/Objectives: Chronic kidney disease (CKD) is associated with increased mortality, with cardiovascular disease (CVD) being the primary cause of death. Proper lipid regulation may reduce CVD risk and slow CKD progression. While there is evidence that a higher plant protein intake could ameliorate lipid levels in the general population, the effects of this dietary regimen within the CKD population remain uncertain, with studies providing conflicting results. We aim to investigate the impact of increased plant protein intake on the lipid levels of CKD patients. Methods: Two electronic databases (PubMed, Scopus) were reviewed for controlled clinical trials assessing the effect of increased plant protein intake versus the usual CKD animal-based diet in CKD patients, published until June 2024. Results: Eleven trials, encompassing 248 patients, were included in this meta-analysis. Overall, compared to the usually recommended CKD diet, increased plant protein intake was associated with statistically significant reductions in total cholesterol (-24.51 mg/dL, 95% CI -40.33, -8.69), low-density lipoprotein (LDL) (-21.71 mg/dL, 95% CI -38.32, -5.1), triglycerides (- 21.88 mg/dL, 95% CI -35.34, -8.40), and Apolipoprotein B levels (-11.21 mg/dL, 95% CI -18.18, -4.25). No significant changes were observed in high-density lipoprotein (HDL) (0.09 mg/dL, 95% CI -1.82, 1.99) and Apolipoprotein A levels (0.04 mg/dL, 95% CI -7.14, 7.21). Conclusions: Increased plant protein intake, mainly from soy, reduces total cholesterol, LDL, triglycerides, and ApoB in adult CKD patients. Further research is needed to assess these effects in dialysis patients and explore non-soy plant sources.

PMID:40362717 | DOI:10.3390/nu17091408

Int J Mol Sci. 2025 May 6;26(9):4401. doi: 10.3390/ijms26094401.

ABSTRACT

Cellular communication network factor 2 (CCN2, also known as CTGF) is a complex protein that regulates numerous cellular functions. This biomolecule exhibits dual functions, depending on the context, and can act as a matricellular protein or as a growth factor. CCN2 is an established marker of fibrosis and a well-known mediator of kidney damage, involved in the regulation of inflammation, extracellular matrix remodeling, cell death, and activation of tubular epithelial cell (TECs) senescence. In response to kidney damage, cellular senescence mechanisms are activated, linked to regeneration failure and progression to fibrosis. Our preclinical studies using a total conditional CCN2 knockout mouse demonstrate that CCN2 plays a significant role in the development of a senescence phenotype after exposure to a nephrotoxic agent. CCN2 induces cell growth arrest in TECs, both in the early phase and in the chronic phase of folic acid nephropathy (FAN), associated with cell-death/necroinflammation and fibrosis, respectively. Renal CCN2 overexpression was found to be linked to excessive collagen accumulation in tubulointerstitial areas, microvascular rarefaction, and a decline in renal function, which were observed three weeks following the initial injury. All these findings were markedly diminished in conditional CCN2 knockout mice. In the FAN model, injured senescent TECs are associated with microvascular rarefaction, and both were modulated by CCN2. In primary cultured endothelial cells, as previously described in TECs, CCN2 directly induced senescence. The findings collectively demonstrate the complexity of CCN2, highlight the pivotal role of cellular senescence as an important mechanism in renal injury, and underscore the critical function of this biomolecule in kidney damage progression.

PMID:40362638 | DOI:10.3390/ijms26094401

Int J Mol Sci. 2025 Apr 29;26(9):4227. doi: 10.3390/ijms26094227.

ABSTRACT

There is an escalating need to comprehend the long-term impacts of nuclear radiation exposure since the permeation of ionizing radiation has been frequent in our current societal framework. A system evaluation of the microbes that reside inside a host's colon could meet this knowledge gap since the microbes play major roles in a host's response to stress. Indeed, our past study suggested that these microbes might break their symbiotic association with moribund hosts to form a pro-survival condition exclusive to themselves. In this study, we undertook metagenomics and metabolomics assays regarding the descending colon content (DCC) of adult mice. DCCs were collected 1 month and 6 months after 7 Gy or 7.5 Gy total body irradiation (TBI). The assessment of the metagenomic diversity profile in DCC found a significant sex bias caused by TBI. Six months after 7.5 Gy TBI, decreased Bacteroidetes were replaced by increased Firmicutes in males, and these alterations were reflected in the functional analysis. For instance, a larger number of networks linked to small chain fatty acid (SCFA) synthesis and metabolism were inhibited in males than in females. Additionally, bioenergy networks showed regression dynamics in females at 6 months post-TBI. Increased accumulation of glucose and pyruvate, which are typical precursors of beneficial SCFAs coupled with the activated networks linked to the production of reactive oxygen species, suggest a cross-sex energy-deprived state. Overall, there was a major chronic adverse implication in male mice that supported the previous literature in suggesting females are more radioresistant than males. The sex-biased chronic effects of TBI should be taken into consideration in designing the pertinent therapeutics.

PMID:40362462 | DOI:10.3390/ijms26094227

Int J Mol Sci. 2025 Apr 28;26(9):4194. doi: 10.3390/ijms26094194.

ABSTRACT

Colorectal cancer (CRC) progression occurs through three stages: adenoma (pre-cancerous lesion), carcinoma in situ (CIS) and adenocarcinoma, with tumor stage playing a pivotal role in the prognosis and treatment outcomes. Despite therapeutic advancements, the lack of stage-specific biomarkers hinders the development of accurate diagnostic tools and effective therapeutic strategies. This study aims to identify stage-specific gene expression profiles and key molecular mechanisms in CRC providing insights into molecular alterations across disease progression. Our methodological approach integrates the use of absolute gene set enrichment analysis (absGSEA) on formalin-fixed paraffin-embedded (FFPE)-derived transcriptomic data, combined with large-scale clinical validation and experimental confirmation. A comparative whole transcriptomic analysis (RNA-seq) was performed on FFPE samples including adenoma (n = 10), carcinoma in situ (CIS) (n = 8) and adenocarcinoma (n = 11) samples. Using absGSEA, we identified significant cellular pathways and putative molecular biomarkers associated with each stage of CRC progression. Key findings were then validated in a large independent CRC patient cohort (n = 1926), with survival analysis conducted from 1336 patients to assess the prognostic relevance of the candidate biomarkers. The key differentially expressed genes were experimentally validated using real-time PCR (RT-qPCR). Pathway analysis revealed that in CIS, apoptotic processes and Wnt signaling pathways were more prominent than in adenoma samples, while in adenocarcinoma, transcriptional co-regulatory mechanisms and protein kinase activity, which are critical for tumor growth and metastasis, were significantly enriched compared to adenoma. Additionally, extracellular matrix organization pathways were significantly enriched in adenocarcinoma compared to CIS. Distinct gene signatures were identified across CRC stages that differentiate between adenoma, CIS and adenocarcinoma. In adenoma, ARRB1, CTBP1 and CTBP2 were overexpressed, suggesting their involvement in early tumorigenesis, whereas in CIS, RPS3A and COL4A5 were overexpressed, suggesting their involvement in the transition from benign to malignant stage. In adenocarcinoma, COL1A2, CEBPZ, MED10 and PAWR were overexpressed, suggesting their involvement in advanced disease progression. Functional analysis confirmed that ARRB1 and CTBP1/2 were associated with early tumor development, while COL1A2 and CEBPZ were involved in extracellular matrix remodeling and transcriptional regulation, respectively. Experimental validation with RT-qPCR confirmed the differential expression of the candidate biomarkers (ARRB1, RPS3A, COL4A5, COL1A2 and MED10) across the three CRC stages reinforcing their potential as stage-specific biomarkers in CRC progression. These findings provide a foundation to distinguish between the CRC stages and for the development of accurate stage-specific diagnostic and prognostic biomarkers, which helps in the development of more effective therapeutic strategies for CRC.

PMID:40362431 | DOI:10.3390/ijms26094194

Int J Mol Sci. 2025 Apr 28;26(9):4168. doi: 10.3390/ijms26094168.

ABSTRACT

The Oxford Nanopore platform and nanopore sequencing are gaining increasing popularity in modern metagenomic research. However, there is a limited set of dedicated tools for analyzing this type of data. The tools used for nanopore amplicon sequencing data analysis often provide only taxonomy annotation without OTU sequence assembly. Conversely, tools that facilitate OTU assembly are constrained in their analysis to long reads, such as the V1-V9 regions of 16S rRNA for bacterial community studies or the full-length ITS cluster (ITS1-5.8S-ITS2) for fungal community studies. In other cases, researchers propose their own solutions without dedicated tools. In this paper, we present Pike, a novel tool for analyzing Oxford Nanopore amplicon sequencing data. Pike allows analysis without amplicon size limitations and allows de novo assembly of OTU sequences. In our research, we created mock communities of fungi and bacteria, which we then used to demonstrate the efficiency of our algorithm. Furthermore, we validated the algorithm using externally available data. We also compared our approach with similar ones to show its applicability.

PMID:40362406 | DOI:10.3390/ijms26094168

Nat Methods. 2025 May 13. doi: 10.1038/s41592-025-02696-1. Online ahead of print.

ABSTRACT

The subcellular localization of a protein is important for its function, and its mislocalization is linked to numerous diseases. Existing datasets capture limited pairs of proteins and cell lines, and existing protein localization prediction models either miss cell-type specificity or cannot generalize to unseen proteins. Here we present a method for Prediction of Unseen Proteins' Subcellular localization (PUPS). PUPS combines a protein language model and an image inpainting model to utilize both protein sequence and cellular images. We demonstrate that the protein sequence input enables generalization to unseen proteins, and the cellular image input captures single-cell variability, enabling cell-type-specific predictions. Experimental validation shows that PUPS can predict protein localization in newly performed experiments outside the Human Protein Atlas used for training. Collectively, PUPS provides a framework for predicting differential protein localization across cell lines and single cells within a cell line, including changes in protein localization driven by mutations.

PMID:40360932 | DOI:10.1038/s41592-025-02696-1

Nat Metab. 2025 May 13. doi: 10.1038/s42255-025-01296-9. Online ahead of print.

ABSTRACT

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis. The Human Cell Atlas Adipose Bionetwork was established to support the generation of single-cell atlases of human AT as well as the development of unified approaches and consensus for cell annotation. Here, we provide a first roadmap from this bionetwork, including our suggested cell annotations for humans and mice, with the aim of describing the state of the field and providing guidelines for the production, analysis, interpretation and presentation of AT single-cell data.

PMID:40360756 | DOI:10.1038/s42255-025-01296-9

Nat Metab. 2025 May 13. doi: 10.1038/s42255-025-01276-z. Online ahead of print.

ABSTRACT

Metabolic reprogramming determines γδ T cell fate during thymic development; however, the metabolic requirements of interleukin (IL)-17A-producing γδ T cells (γδT17 cells) under psoriatic conditions are unclear. Combining high-throughput techniques, including RNA sequencing, SCENITH, proteomics and stable isotope tracing, we demonstrated that psoriatic inflammation caused γδT17 cells to switch toward aerobic glycolysis. Under psoriatic conditions, γδT17 cells upregulated ATP-citrate synthase to convert citrate to acetyl-CoA, linking carbohydrate metabolism and fatty acid synthesis (FAS). Accordingly, we used a pharmacological inhibitor, Soraphen A, which blocks acetyl-CoA carboxylase (ACC), to impair FAS in γδT17 cells, reducing their intracellular lipid stores and ability to produce IL-17A under psoriatic conditions in vitro. We pinpointed the pathogenic role of ACC1 in γδT17 cells in vivo by genetic ablation, ameliorating inflammation in a psoriatic mouse model. Furthermore, ACC inhibition limited human IL-17A-producing γδT17 cells. Targeting ACC1 to attenuate pathogenic γδT17 cell function has important implications for psoriasis management.

PMID:40360755 | DOI:10.1038/s42255-025-01276-z

Cell Death Discov. 2025 May 13;11(1):234. doi: 10.1038/s41420-025-02405-z.

ABSTRACT

Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer.

PMID:40360465 | DOI:10.1038/s41420-025-02405-z

RNA. 2025 May 13:rna.080561.125. doi: 10.1261/rna.080561.125. Online ahead of print.

ABSTRACT

Processing bodies (P-bodies) are membrane-less organelles in eukaryotic cells that play a central role in mRNA metabolism, including mRNA decay, storage, and translational repression. However, the molecular mechanisms governing their assembly remain incompletely understood. Here, we identify the C-terminal domain of EDC4 as the minimal region required for P-body formation, with residues 1266-1401 driving phase separation and EDC4 condensation. To investigate the functional relevance of P-body integrity, we employed the microprotein Nobody (NBDY) as a selective perturbation tool. Our results revealed that the NBDY 22-41 peptide directly binds the EDC4 C-terminal domain and inhibits its self-association, thereby selectively dissolving P-bodies without affecting the canonical mRNA decay pathway. Using this tool, we further examined the impact of P-body disruption on gene expression. Transcriptome profiling combined with quantitative validation revealed that P-body loss activates the p53 pathway and enhances the stability of associated transcripts. Consistent with these findings, clinical data show that NBDY overexpression is associated with p53 pathway activation in various cancers, and the NBDY 22-41 fragment reduces tumor cell proliferation and invasion, suggesting a potentially complex role of P-body dynamics in cancer biology. Together, our study defines the EDC4 C-terminal domain as a core scaffold for P-body assembly and uncovers a regulatory role of P-body dynamics in p53-mediated gene expression, with potential implications for cancer biology.

PMID:40360209 | DOI:10.1261/rna.080561.125

Genome Res. 2025 May 13. doi: 10.1101/gr.279398.124. Online ahead of print.

ABSTRACT

The relationship between TP53 and transposable elements (TEs) has been obscure. Given the important role of TEs in oncogenesis, a comprehensive profiling of TE expression dynamics under the regulation of TP53 provides valuable resources for more clarity in TP53's roles in cancer. In this study, we characterized the TE transcriptomic landscape using long-read RNA-seq and short-read RNA-seq in three cancer cell lines varying only in TP53 genetic status. To identify transcripts that use TEs as potential promoters, we developed a computational pipeline, TEProf3, and identified in total 1942 transcripts with high confidence. Among these TE-derived transcripts, 239 are activated by TP53 and 221 are repressed by TP53. These TP53-responsive TE-derived transcripts are mainly driven by members of the ERV and LINE families. Following knockdown of wild-type (WT) TP53 expression, rescuing WT TP53 expression allows for partial recovery of the TE expression profile observed in the context of chronic TP53 expression. TP53 mutations R175H and R273H manifest their oncogenic characteristic partially through activating TE promoters in a cell type-specific manner. Lastly, we identified important sequence motifs that help govern the interactions between TEs and TP53, where TP53 activates TEs with TP53 binding motifs through direct binding and represses TEs indirectly via other pathways. Overall, we present a comprehensive profiling of the impact of TP53 on the activity of TE-derived promoters in isogenic cancer cell lines and provide a high-confidence TE expression atlas of TE promoters that are direct and indirect targets of TP53.

PMID:40360186 | DOI:10.1101/gr.279398.124

Brief Bioinform. 2025 May 1;26(3):bbaf211. doi: 10.1093/bib/bbaf211.

ABSTRACT

Traits in any organism are not independent, but show considerable integration, observed in a form of couplings and trade-offs. Therefore, improvement in one trait may affect other traits, often in undesired direction. To account for this problem, crop breeding increasingly relies on multi-trait genomic prediction (MT-GP) approaches that leverage the availability of genetic markers from different populations along with advances in high-throughput precision phenotyping. While significant progress has been made to jointly model multiple traits using a variety of statistical and machine learning approaches, there is no systematic comparison of advantages and shortcomings of the existing classes of MT-GP models. Here, we fill this knowledge gap by first classifying the existing MT-GP models and briefly summarizing their general principles, modeling assumptions, and potential limitations. We then perform an extensive comparative analysis with 10 traits measured in an Oryza sativa diversity panel using cross-validation scenarios relevant in breeding practice. Finally, we discuss directions that can enable the building of next generation MT-GP models in addressing pressing challenges in crop breeding.

PMID:40358423 | DOI:10.1093/bib/bbaf211

Nucleic Acids Res. 2025 May 13:gkaf402. doi: 10.1093/nar/gkaf402. Online ahead of print.

ABSTRACT

BioPortal (https://bioportal.bioontology.org) is the world's most comprehensive repository of biomedical ontologies. It provides infrastructure for finding, sharing, searching, and utilizing biomedical ontologies. Launched in 2005, BioPortal now includes 1549 ontologies (1182 of them public). Its open, freely accessible website enables anyone (i) to browse the ontology library, (ii) to search for terms across ontologies, (iii) to browse mappings between terms, (iv) to see popularity ratings and recommendations on which ontologies are most relevant to their use cases, (v) to annotate text with ontology terms, (vi) to submit an ontology, and (vii) to request ontology changes. The library of ontologies can be accessed programmatically via a REST application programming interface (API). Recent enhancements include a BioPortal knowledge graph that integrates knowledge from multiple ontologies; a unified data model for interoperability with other knowledge sources; ontology popularity ratings and recommendations for relevant ontologies; and the ability to request ontology changes via a simple user interface that automatically converts user change requests to GitHub Pull Requests that specify the edits that will be made to the ontology upon approval.

PMID:40357648 | DOI:10.1093/nar/gkaf402

Front Neurosci. 2025 Apr 28;19:1534061. doi: 10.3389/fnins.2025.1534061. eCollection 2025.

ABSTRACT

Bridge-like lipid transporters (BLTPs) have recently been revealed as key regulators of intraorganellar lipid trafficking, with their loss being associated with defective synaptic signalling and congenital neurological diseases. This group consists of five protein subfamilies [BLTP1-3, autophagy-related 2 (ATG2), and vacuolar protein sorting 13 (VPS13)], which mediate minimally selective lipid transfer between cellular membranes. Deceptively simple in both structure and presumed function, this review addresses open questions as to how bridge-like transporters work, the functional consequences of bulk lipid transfer on cellular signalling, and summarises some recent studies that have shed light on the surprising level of regulation and specificity found in this family of transporters.

PMID:40356703 | PMC:PMC12066543 | DOI:10.3389/fnins.2025.1534061

Front Microbiol. 2025 Apr 28;16:1568162. doi: 10.3389/fmicb.2025.1568162. eCollection 2025.

ABSTRACT

The potential of phosphate-solubilizing microbes (PSMs) to enhance plant phosphorus uptake and reduce fertilizer dependency remains underutilized. This is partially attributable to frequent biofertilizer-farming system misalignments that reduce efficacy, and an incomplete understanding of underlying mechanisms. This study explored the seed microbiomes of nine Australian lucerne cultivars to identify and characterize high-efficiency PSMs. From a library of 223 isolates, 94 (42%) exhibited phosphate solubilization activity on Pikovskaya agar, with 15 showing high efficiency (PSI > 1.5). Genomic analysis revealed that the "high-efficiency" phosphate-solubilizing microbes belonged to four genera (Curtobacterium, Pseudomonas, Paenibacillus, Pantoea), including novel strains and species. However, key canonical genes, such as pqq operon and gcd, did not reliably predict phenotype, highlighting the limitations of in silico predictions. Mutagenesis of the high-efficiency isolate Pantoea rara Lu_Sq_004 generated mutants with enhanced and null solubilization phenotypes, revealing the potential role of "auxiliary" genes in downstream function of solubilization pathways. Inoculation studies with lucerne seedlings demonstrated a significant increase in shoot length (p < 0.05) following treatment with the enhanced-solubilization mutant, indicating a promising plant growth-promotion effect. These findings highlight the potential of more personalized "system-appropriate" biofertilizers and underscore the importance of integrating genomic, phenotypic, and in planta analyses to validate function. Further research is required to investigate links between genomic markers and functional outcomes to optimize the development of sustainable agricultural inputs.

PMID:40356655 | PMC:PMC12066602 | DOI:10.3389/fmicb.2025.1568162

Elife. 2025 May 13;14:e79517. doi: 10.7554/eLife.79517.

ABSTRACT

Bacterial persistence is a phenomenon in which a small fraction of isogenic bacterial cells survives a lethal dose of antibiotics. Although the refractoriness of persistent cell populations has classically been attributed to growth-inactive cells generated before drug exposure, evidence is accumulating that actively growing cell fractions can also generate persister cells. However, single-cell characterization of persister cell history remains limited due to the extremely low frequencies of persisters. Here, we visualize the responses of over one million individual cells of wildtype Escherichia coli to lethal doses of antibiotics, sampling cells from different growth phases and culture media into a microfluidic device. We show that when cells sampled from exponentially growing populations were treated with ampicillin or ciprofloxacin, most persisters were growing before antibiotic treatment. Growing persisters exhibited heterogeneous survival dynamics, including continuous growth and fission with L-form-like morphologies, responsive growth arrest, or post-exposure filamentation. Incubating cells under stationary phase conditions increased both the frequency and the probability of survival of non-growing cells to ampicillin. Under ciprofloxacin, however, all persisters identified were growing before the antibiotic treatment, including samples from post-stationary phase culture. These results reveal diverse persister cell dynamics that depend on antibiotic types and pre-exposure history.

PMID:40356339 | DOI:10.7554/eLife.79517