Search Results (54)

This study comprehensively characterizes the PEBP gene family in Cymbidium sinense, an orchid with a prolonged vegetative phase that limits its industrial production. Genome-wide analysis identified six CsPEBPs, classified into FT-like, TFL1-like, and MFT-like subfamilies. Evolutionary, gene structure, and collinearity analyses revealed both conservation and lineage-specific diversification of these genes. CsFTL3, a distinctive FT-like member, displayed notably high expression during the bud undifferentiated stage, followed by a sharp downregulation upon floral initiation. Functional studies identified CsFTL3 as a key floral repressor. Heterologous overexpression in Arabidopsis delayed flowering time from 32.0 days (wild-type) to 63.0–75.3 days (transgenic) and increased rosette leaf number from 12.6 to 33.0–34.5, while its knockdown via virus-induced gene silencing (VIGS) in C. sinense accelerated floral bud development and upregulated flowering-promoter genes. Phylogenetically, CsFTL3 falls within the flowering repressor FT-I clade, and multiple sequence alignment identified critical amino acid substitutions (Y134S, W138L, Q140E) that likely underpin its functional divergence from typical flowering promoters. Furthermore, promoter analysis revealed an enrichment of light-, hormone-, and stress-responsive cis-elements, and its expression was modulated by gibberellin (GA), abscisic acid (ABA), and low-temperature treatments. Predicted protein–protein interaction and transcriptional regulatory networks provide preliminary insights into its complex regulation. We conclude that CsFTL3 acts as a crucial floral inhibitor, integrating environmental and endogenous cues to repress flowering. These findings offer fundamental insights into the molecular mechanisms of flowering in orchids and provide a valuable genetic resource for molecular breeding programs aimed at achieving precise flowering time control. Full article

Across plants, the PEBP gene family is reported to regulate storage organ formation, developmental plasticity, and floral transitioning. However, its evolutionary dynamics and functional diversification within Allium species remain poorly understood. In this study, we performed genomic and transcriptomic analyses of the PEBP gene family across three economically important Allium species, including Allium fistulosum (bunching onion), Allium sativum (garlic), and Allium cepa (onion), identifying 19, 17, and 21 PEBP genes, respectively. The genes were assigned into five subfamilies (FT-like, TFL1-like, MFT-like, BFT-like, and PEBP-like), with MFT-like members being the most abundant. Structural analysis revealed strong conservation of key motifs (e.g., GxHR and DPDxP) across species, while substantial variation in intron–exon organization suggested subfunctionalization. Collinearity analysis indicated that segmental duplication primarily drove PEBP gene expansion in garlic and onion, whereas tandem duplication was absent in bunching onion. Promoter analysis showed enrichment of light- and hormone-related cis-regulatory elements, implicating their involvement in environmental and hormonal regulation. Expression profiling demonstrated clear tissue specificity, with AsPEBP11/13/14/16/19 exhibiting significantly higher expression in normal flowers than in abnormal ones, suggesting key roles in floral morphogenesis. Together, these findings will prove useful for future breeding programs aimed at improving reproductive development and fertility in Allium species. Full article

Background: Ovarian cancer is characterized by high mortality rates, primarily due to diagnosis at late stages. Current biomarkers, such as CA125, have demonstrated limited efficacy for early detection. While high-dimensional proteomics offers a more comprehensive view of systemic biology, the analysis of such data, where the number of features far exceeds the number of samples, presents a significant computational challenge. Methods: This study utilized a nested case–control cohort of longitudinal pre-diagnostic serum samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) profiled for eight candidate ovarian cancer biomarkers (CA125, HE4, PEBP4, CHI3L1, FSTL1, AGR2, SLPI, DNAH17) and 92 additional cancer-associated proteins from the Olink Oncology II panel. We employed a Synolitic Graph Neural Network framework that transforms high-dimensional multi-protein data into sample-specific, interconnected graphs using a synolitic network approach. These graphs, which encode the relational patterns between proteins, were then used to train Graph Neural Network (GNN) models for classification. Performance of the network approach was evaluated together with conventional machine learning approaches via 5-fold cross-validation on samples collected within one year of diagnosis and a separate holdout set of samples collected one to two years prior to diagnosis. Results: In samples collected within one year of ovarian cancer diagnosis, conventional machine learning models—including XGBoost, random forests, and logistic regression—achieved the highest discriminative performance, with XGBoost reaching an ROC-AUC of 92%. Graph Convolutional Networks (GCNs) achieved moderate performance in this interval (ROC-AUC ~71%), with balanced sensitivity and specificity comparable to mid-performing conventional models. In the 1–2 year early-detection window, conventional model performance declined sharply (XGBoost ROC-AUC 46%), whereas the GCN maintained robust discriminative ability (ROC-AUC ~74%) with relatively balanced sensitivity and specificity. These findings indicate that while conventional approaches excel at detecting late pre-diagnostic signals, GNNs are more stable and effective at capturing subtle early molecular changes. Conclusions: The synolitic GNN framework demonstrates robust performance in early pre-diagnostic detection of ovarian cancer, maintaining accuracy where conventional methods decline. These results highlight the potential of network-informed machine learning to identify subtle proteomic patterns and pathway-level dysregulation prior to clinical diagnosis. This proof-of-concept study supports further development of GNN approaches for early ovarian cancer detection and warrants validation in larger, independent cohorts. Full article

Robin sequence (RS) is a rare congenital anomaly characterized by micrognathia, glossoptosis, and upper airway obstruction (UAO), often accompanied by a cleft palate. The Tübingen Palatal Plate (TPP), also referred to as the pre-epiglottic baton plate (PEBP), offers a non-surgical, functional orthodontic solution that improves airway patency and feeding by advancing the tongue base. This paper outlines the semi-digital clinical and technical workflow used for TPP treatment at Tübingen University Hospital. The protocol combines intraoral scanning (IOS), computer-aided design and manufacturing (CAD/CAM), and manual refinement for patient-specific appliance production. Practical steps, modifications for special cases and follow-up procedures are detailed, aiming to support clinical implementation at other centres. Based on the published literature and over three decades of experience, the protocol emphasizes safety, quality control, and interdisciplinary collaboration, with practical guidance provided to support implementation in other centres. The potential of digital workflows for data sharing, training, and multicenter collaboration is highlighted, while challenges such as the need for specialized expertise and technical resources are acknowledged. This guideline provides the first comprehensive and reproducible description of the Tübingen approach and aims to facilitate wider adoption of TPP therapy for infants with RS. Full article

RKIP and LKB1, encoded by PEBP1 and STK11, respectively, have emerged as key regulators of cancer pathophysiology. However, their role in shaping tumor progression through modulation of the tumor microenvironment (TME) is not yet fully understood. To address this, we performed a comprehensive pan-cancer analysis using TCGA transcriptomic data across 33 cancer types, grouped by their tissue of origin. We investigated PEBP1/STK11 co-expression and its association with transcriptomic reprogramming in major TME components, including immune, mechanical, metabolic, and hypoxic subtypes. Our results revealed both positive and inverse correlations between PEBP1/STK11 co-expression and TME-related molecular signatures, which did not align with classical cancer categorizations. In a subset of tumors, PEBP1/STK11 co-expression was significantly associated with improved overall survival and reduced mortality (HR < 1). Notably, we predominantly observed inverse correlations with pro-inflammatory and immunosuppressive chemokines, immune checkpoints, extracellular matrix components, and key regulators of epithelial-to-mesenchymal transition. In contrast, we found positive associations with anti-inflammatory chemokines and their receptors. Importantly, PEBP1/STK11 co-expression was consistently linked to reduced expression of drug resistance genes and greater chemosensitivity across multiple tumor types. Our findings underscore the co-expression of PEBP1 and STK11 as a promising target for future studies aimed at elucidating its potential as a biomarker for prognosis and therapeutic response in precision oncology. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article

The phosphatidylethanolamine-binding protein (PEBP) gene family, known for its pivotal role in controlling floral transition, regulates flowering time, and, thus, shapes the continuous-flowering trait in ornamental plants. In this study, we conducted the first genome-wide identification and bioinformatics analysis of the PEBP gene family in Begonia semperflorens ‘Super Olympia’, a variety that exhibits year-round flowering. Via phylogenetic analysis, a total of 10 BsPEBP genes were identified and categorized into four subfamilies: the FT-like (two members), TFL1-like (three members), PEBP-like (three members), and MFT-like (two members) subfamilies. Gene structure analysis revealed highly conserved motif compositions among family members, and protein tertiary structure prediction indicated the dominance of random coils in their structures. Promoter cis-acting element analysis revealed light-responsive, hormone-responsive (ABA, GA, and JA), and abiotic stress-responsive elements in the BsPEBP genes, suggesting their potential integration into multiple regulatory pathways. The tissue-specific expression profiles revealed that BsPEBP6 was significantly upregulated in floral organs, whereas TFL1-like subfamily members were predominantly expressed in vegetative tissues. These findings imply that the FT-like and TFL1-like genes antagonistically regulate the continuous-flowering trait of B. semperflorens ‘Super Olympia’ through their respective roles in promoting and repressing flowering. Our findings provide a preliminary theoretical foundation for elucidating the molecular mechanisms by which the PEBP gene family regulates flowering time in ornamental plants and offer valuable insights for developing breeding strategies aimed at flowering time modulation. Full article

Background: Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated in the pathogenesis of asthma. The ferroptosis markers PEBP1 and 15-LO-1 are increasingly recognized as potential biomarkers for asthma. This study investigates the association of these markers with asthma and its severity to evaluate their diagnostic potential. Methods: This cross-sectional study included 45 asthmatic patients and 45 healthy controls. Serum phosphatidylethanolamine-binding protein 1 (PEBP1) and 15-lipoxygenase-1 (15-LO-1) levels were measured using ELISA. Spirometric parameters (FEV₁, FEV₁/FVC ratio, and PEFR) were recorded. A multivariate regression assessed associations between ferroptosis markers and asthma severity. A generalized linear model (GLM) analyzed the relationship between biomarkers (PEBP1 and 15-LO-1) and lung function parameters. A receiver operating characteristic (ROC) analysis evaluated the discriminative capacity of PEBP1 and 15-LO-1. Results: PEBP1 and 15-LO-1 levels were significantly associated with asthma. The multivariate analysis revealed that low PEBP1 levels were strongly associated with asthma and severe asthma (p < 0.001). While elevated 15-LO-1 levels were associated with asthma (p < 0.001), they did not correlate with severity. The ROC analysis demonstrated excellent discriminative capacity for PEBP1 (AUC 0.962, cutoff 1509.8 pg/mL) and 15-LO-1 (AUC 0.895, cutoff 144.8 pg/mL). Lower PEBP1 and higher 15-LO-1 levels were associated with reduced lung function, and lower FEV₁, FEV₁/FVC, and PEF. Older age and female gender were associated with severe asthma. Conclusions: PEBP1 and 15-LO-1 are promising biomarkers for asthma, with PEBP1 showing strong correlations with asthma severity. These findings highlight the potential role of ferroptosis markers in asthma and underscore the need for further longitudinal studies to explore these markers’ clinical utility in personalized asthma management. Full article

The phosphatidylethanolamine-binding protein (PEBP) gene family is critical for regulating plant growth, development, and flowering. Sunflower (Helianthus annuus L.) is the fourth most important oilseed crop globally. However, the genomic structure and functional diversity of PEBP genes in sunflower remain unexplored. Leveraging the recently assembled telomere-to-telomere (T2T) sunflower genome, a genome-wide analysis of the HaPEBP family was carried out. A total of 12 PEBP genes were identified in sunflower and categorized into three subfamilies: TFL1-like, FT-like, and MFT-like. Phylogenetic and synteny analyses revealed that tandem duplication events have substantially contributed to the evolution and expansion of the HaPEBP gene family. Furthermore, the analysis of the promoter regions revealed 77 distinct cis-acting elements, including 35 related to light signaling and growth regulation, highlighting their potential involvement in the regulation of flowering and development in sunflower. Expression profile analysis using RNA-seq data across various tissues indicated that FT-like and TFL1-like HaPEBP genes may be the key regulators of flowering time and plant architecture in sunflower varieties. This study offers valuable insights into the structural, evolutional, and functional dynamics of the HaPEBP gene family and holds significant implications for sunflower breeding strategies aimed at optimizing flowering time and plant architecture traits. Full article

Globe artichoke [Cynara cardunculus var. scolymus (L.)] is a perennial composite cultivated for its immature inflorescences. Over time, the market for growers has steadily shifted away from vegetatively propagated varieties and towards seed-propagated hybrids. Since the latter tend to produce relatively late in the season, advancing the moment of flowering remains a major objective for breeders, who can benefit from insight gained into the genetic architecture of this trait. In plants, the timing of flowering is strongly regulated at the genetic level to ensure reproductive success. Genetic studies in model and non-model species have identified gene families playing crucial roles in flowering time control. One of these is the phosphatidylethanolamine-binding protein (PEBP) family, a conserved group of genes that, in plants, not only regulate the vegetative-to-reproductive phase transition, but also the development of inflorescences. In this work, we identified seven PEBP family members in the globe artichoke genome, belonging to three major clades: MOTHER OF FT AND TFL1 (MFT)-like, TERMINAL FLOWER 1 (TFL1)-like, and FLOWERING LOCUS T (FT)-like. Our results further show that CcFT expression is upregulated after the floral transition and partially complements the ft-10 mutant, whilst CcTFL1 is expressed in the shoot apex and developing inflorescences and complements the tfl1-1 mutant. These results suggest that the flowering-suppressing function of CcTFL1 is conserved in globe artichoke whereas conservation of the floral promoting function of CcFT remains uncertain. Full article

Human nutrition is inherently associated with the cultivation of vegetables, grains, and fruits, underscoring the critical need to understand and manipulate the balance between vegetative and reproductive development in plants. Despite the vast diversity within the plant kingdom, these developmental processes share conserved and interconnected pathways among angiosperms, predominantly involving age, vernalization, gibberellin, temperature, photoperiod, and autonomous pathways. These pathways interact with environmental cues and orchestrate the transition from vegetative growth to reproductive stages. Related to this, there are two key genes belonging to the same Phosphatidylethanolamine-binding proteins family (PEBP), the FLOWERING LOCUS T (FT) and TERMINAL FLOWER 1 (TFL1), which activate and repress the floral initiation, respectively, in different plant species. They compete for transcription factors such as FLOWERING LOCUS D (FD) and 14-3-3 to form floral activation complexes (FAC) and floral repression complexes (FRC). The FT/TFL1 mechanism plays a pivotal role in meristem differentiation, determining developmental outcomes as determinate or indeterminate. This review aims to explore the roles of FT and TFL1 in plant architecture and floral induction of annual and perennial species, together with their interactions with plant hormones. In this context, we propose that plant development can be modulated by the response of FT and/or TFL1 to plant growth regulators (PGRs), which emerge as potential tools for mitigating the adverse effects of environmental changes on plant reproductive processes. Thus, understanding these mechanisms is crucial to address the challenges of agricultural practices, especially in the face of climate change. Full article

Background/Objectives: Carrot is a major root vegetable in the Apiaceae owing to its abundant carotenoids, antioxidants, vitamins, and minerals. The modern dark orange western carrot was derived from sequential domestication events from the white-rooted wild form to the pale orange-, purple-, or yellow-rooted eastern carrot. Genetic and molecular studies between eastern and western carrots are meager despite their evolutionary relatedness. Methods: Twelve RNA seq libraries obtained from distinct eastern and western cultivars at vegetative and reproductive developmental stages were utilized to identify differentially expressed genes (DEGs) to decode the key molecular genetic changes in carotenoid and flowering pathways. Results: In the carotenoid pathway, an upregulation of the PSY, CRTISO, and LCYE genes was observed in the western cultivar, while the eastern cultivar exhibited a higher abundance of downstream enzymes, particularly CCD and NCED1. These later enzymes are crucial in linking apocarotenoids and xanthin-mediated ABA signaling. In the flowering pathway, we noted a greater expression of DEGs associated with the photoperiod and vernalization pathways in the western cultivar. In contrast, the eastern cultivar displayed a dominance of genes from the autonomous pathway (FLD, LD, FLK, and PEBP) that function to repress FLC. The experimental validation of 12 key genes through quantitative real-time PCR further confirms their functional role in carrots. Conclusions: The identified key regulatory genes in these major pathways are valuable for designing breeding strategies for manipulating carotenoid content and flowering time while developing climate-specific carrots. The knowledge of carotenoid and flowering pathways is advantageous in producing nutritionally improved roots and seeds in carrots across diverse climates. Full article

Phosphatidylethanolamine-binding proteins (PEBPs) play a crucial role in the growth and development of various organisms. Due to the low sequence similarity compared to plants, humans, and animals, the study of pebp genes in fungi has not received significant attention. The redifferentiation of fruiting bodies is exceedingly rare in fungal development. Hitherto, only a few studies have identified the Capebp2 gene as being associated with this phenomenon in Cyclocybe aegerita. Thus, exploring the role of pebp genes in fruiting body development is imperative. In the present study, four Capebp genes (Capebp1, Capebp3, Capebp4, and Capebp5) were cloned from the AC0007 strain of C. aegerita based on genome sequencing and gene prediction. The findings indicate that the pebp family, in C. aegerita, comprises a total of five genes. Moreover, the sequence similarity was low across the five CAPEBP protein sequences in C. aegerita, and only a few conserved sequences, such as HRY and RHF, were identical. Expression analyses revealed that, similarly to Capebp2, the four Capebp genes exhibit significantly higher expression levels in the fruiting bodies than in the mycelium. Furthermore, overexpressed and RNA interference Capebp1 or Capebp5 transformants were analyzed. The results demonstrate that overexpression of Capebp1 or Capebp5 could induce the regeneration of the lamella or fruiting body, whereas the knockdown of Capebp1 or Capebp5 could lead to the accelerated aging of fruiting bodies. These findings highlight a significant role of Capebp genes in the generation of C. aegerita fruiting bodies and provide a foundation for further exploration into their involvement in basidiomycete growth and development. Full article

The implementation of e-jeepneys stands as a change process that will eventually transition to the modernization of the public transport system in the Philippines. To address concerns about jeepneys’ effects on the environment, energy use, society, the economy, and policies, their acceptability in the Philippines must be considered. This research study aims to identify the sources of influence on Filipinos’ adoption of e-jeepney utilization as a mode of transportation using the extended Pro-Environmental Planned Behavior (PEBP) model. A total of 502 commuters voluntarily answered the survey questionnaire. Based on the findings, perceived environmental concern (PEC) is the most significant determinant influencing attitude (AT) and, thus, affecting the Filipinos’ behavioral intention (BI) towards the adoption of e-jeepneys. Conversely, AT was the primary determinant of BI, which strongly supported the notion of AT as a strong driving force shaping behavioral decisions. Moreover, perceived authority support (PAS) emerged as a strong predictor of subjective norms (SNs), demonstrating the influence of institutional support on societal perceptions. As a result, more environmentally conscious people are more likely to view e-jeepneys positively and intend to use them as a mode of transportation. The endorsement or support from authoritative figures or institutions notably influences subjective norms, which are individuals’ perceptions of social pressures regarding the use of e-jeepneys. Full article

The family of phosphatidylethanolamine-binding proteins (PEBPs) participates in various plant biological processes, mainly flowering regulation and seed germination. In cucurbit crops, several PEBP genes have been recognized to be responsible for flowering time. However, the investigation of PEBP family members across the genomes of cucurbit species has not been reported, and their conservation and divergence in structure and function remain largely unclear. Herein, PEBP genes were identified from seven cucurbit crops and were used to perform a comparative genomics analysis. The cucurbit PEBP proteins could be classified into MFT, FT, TFL, and PEBP clades, and further, the TFL clade was divided into BFT-like, CEN-like, and TFL1-like subclades. The MFT-like, FT-like, and TFL-like proteins were clearly distinguished by a critical amino acid residue at the 85th position of the Arabidopsis FT protein. In gene expression analysis, CsaPEBP1 was highly expressed in flowers, and its expression levels in females and males were 70.5 and 89.2 times higher, respectively, than those in leaves. CsaPEBP5, CsaPEBP6, and CsaPEBP7 were specifically expressed in male flowers, with expression levels 58.1, 17.3, and 15.7 times higher, respectively, than those of leaves. At least five CsaPEBP genes exhibited the highest expression during the later stages of corolla opening. Through clustering of time-series-based RNA-seq data, several potential transcription factors (TFs) interacting with four CsaPEBPs were identified during cucumber corolla opening. Because of the tandem repeats of binding sites in promoters, NF-YB (Csa4G037610) and GATA (Csa7G64580) TFs appeared to be better able to regulate the CsaPEBP2 and CsaPEBP5 genes, respectively. This study would provide helpful information for further investigating the roles of PEBP genes and their interacting TFs in growth and development processes, such as flowering time regulation in cucurbit crops. Full article