Search Results (716)

Transcription is a core hallmark of cancer, wherein many different proteins assemble at specific sites in the nucleus and act in concert to transcribe functionally relevant genes. Central to this process are transcription factors that bind to their cognate DNA motifs on enhancers and super-enhancers to recruit cofactors, coactivators, and epigenetic modifiers, thereby inducing or repressing gene expression. Super-enhancers drive oncogenic transcription, to which cancer cells become highly addicted and confer tumor dependencies on super-enhancer-driven transcription machinery. Transcriptional condensates (TCs) are nuclear membrane-less assemblies of DNA-binding transcription factors, transcription co-activators, and the transcriptional machinery (such as RNA polymerases, non-coding RNAs) formed through liquid–liquid phase separation (LLPS). The function of transcriptionally active oncogenic proteins and their interplay with nucleic acids are carried out within these biomolecular condensates, allowing them to spatiotemporally regulate oncogene expression and lead to the induction and maintenance of cancer. With this growing understanding, specific inhibitors and strategies targeting TC assembly and activation should be considered promising therapeutic opportunities for treating various tumors, including hematological malignancies. Full article

Efficient allocation of mineral nutrients and photoassimilates is essential for grain development in rice. However, the transcriptional programs governing nutrient transport at key reproductive stages remain largely unresolved. Here, we performed a comprehensive transcriptome analysis of rice (Oryza sativa L.) across spatial (nodes, roots, and five other tissues) and temporal (seven reproductive stages) dimensions to elucidate the molecular basis of nutrient transport and allocation. RNA-seq profiling of node I identified stage-specific gene expression patterns, with the grain filling stage marked by strong induction of transporters involved in mineral allocation (e.g., OsYSL2, OsZIP3, OsSULTR3;3, SPDT) and carbohydrate distribution (e.g., OsSWEET13, OsSWEET14, OsMST6). Comparative analysis with the neck-panicle node (NPN) and root revealed tissue-specific regulatory networks, including nitrate (OsNRT1.1A, OsNRT2.3) and phosphate (OsPHT1;4, OsPHO1;3) transporters enriched at the grain filling stage. Root expression of Cd/As-related transporters (OsNRAMP5, OsCd1, OsLsi1, OsLsi2, OsLsi3) during grain filling highlights the contribution of belowground uptake to grain metal accumulation. Together, our study establishes a spatiotemporal atlas of nutrient transporter gene activity during rice reproductive development and identifies candidate genes regulating upward and lateral nutrient allocation. These findings provide insights into improving nutrient use efficiency and reducing toxic metal accumulation in rice grains through targeted manipulation of nodal and root transport systems. Full article

The wool of sheep consists of structurally intricate natural fibres that can be processed and manufactured into a range of products. It is prized for its insulation, moisture-buffering capability, flame resistance, and biodegradability. These features arise from its unique fibre architecture and specialised protein composition, which set it apart from most other natural and synthetic fibres. However, despite these novel characteristics, wool fibre variation hampers its uses and reduces its ability to compete with other fibres. This review summarises our current knowledge of wool fibre biology. It begins with a description of wool’s functional properties and performance attributes, then explores the structural foundations of these properties, the molecular basis of fibre trait variation, and prospects for improving fibre quality using genetic approaches. Particular attention is given to the wool keratin and keratin-associated protein genes, their spatiotemporal expression patterns, and genetic polymorphism that may influence fibre characteristics. Opportunities for the genetic improvement of sheep are discussed, including the use of genetic modification and marker-assisted selection. Challenges in interpreting gene–trait associations, particularly from high-throughput omics studies, are highlighted, along with the need for functionally validated genetic markers. Potential trade-offs between wool characteristics and other production and reproductive traits are considered, emphasising the need for balanced breeding approaches. By integrating insights from structural biology, molecular genetics, and breeding strategies, this review provides a foundation for wool fibre improvement. Full article

Von Willebrand factor A (vWA) genes play important roles in regulating plant growth and development, as well as biotic stresses. However, limited data are available on the contributions of vWA genes to wheat (Triticum aestivum L.). In this study, 114 TavWA genes were identified in the wheat genome, which were unevenly distributed on 21 chromosomes. According to the phylogenetic analysis, the 114 TavWAs were classified into six groups, two of which (G3 and G6) were unique to wheat. Fifty-five homoeologous gene sets among A, B, and D sub-genomes were detected, which play a crucial role in the expansion of the wheat vWA gene family. Analysis of specific spatiotemporal expression patterns showed that more than 50% of TavWAs (61 out of 114) exhibited tissue-specific expression. These included 71 TavWAs that responded to one or more of the four biotic stress treatments (flg22, chitin, powdery mildew, and stripe rust). Notably, these included TavWA1-7D, a recently reported key growth regulator in wheat, suggesting its additional role in biotic stress responses. RT-qPCR analysis indicated that eight genes (TavWA1-7D, TavWA24-2B, TavWA36-1D, TavWA37-7D, TavWA40, TavWA47, TavWA51, and TavWA53) may play important roles in wheat’s powdery mildew resistance. Collectively, the results of this study provide significant insights for future research on the involvement of vWA genes in the development and stress responses of wheat. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. However, the spatial and temporal dynamics underlying its development remain poorly characterized. This study employs spatial transcriptomics (ST) to investigate the progression of intestinal tumors in APC ^Min/+ mice across multiple time points. We identified distinct transcriptional profiles between tumor and normal tissues, resolving six major cell types through integrated dimensionality reduction and pathological annotation. Pseudo-time trajectory analysis revealed increased expression of MMP11 and MYL9 in later stages of tumor progression. Analysis of human CRC cohorts from the TCGA database further confirmed that high expression of these genes is associated with advanced clinical stages and promotes tumor proliferation and invasion. Temporal gene expression dynamics indicated enrichment of cancer-related pathways concurrent with suppression of lipid and amino acid metabolism. Notably, genes in the DEFA family were significantly upregulated in normal tissues compared to tumor tissues. Functional validation showed that DEFA3 inhibits colon cancer cell migration and proliferation in vitro. These demonstrate the value of ST in resolving spatiotemporal heterogeneity in CRC and identify both MMP11/MYL9 and DEFA3 as potential biomarkers and therapeutic targets. Full article

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease caused by mutations in the DMD gene, leading to muscle degeneration and shortened life expectancy. Beyond motor symptoms, DMD patients frequently exhibit brain co-morbidities, linked to loss of brain-expressed dystrophin isoforms: most frequently Dp427 and Dp140, and occasionally Dp71 and Dp40. DMD mouse models, including mdx^5cv and mdx52, replicate key aspects of the human cognitive phenotype and recapitulate the main genotypic categories of brain phenotype. However, the spatio-temporal expression of brain dystrophin in mice remains poorly defined, limiting insights into how its deficiency disrupts brain development and function. We systematically mapped RNA and protein expression of brain dystrophin isoforms (Dp427 variants, Dp140, Dp71, and Dp40) across brain regions and developmental stages in wild-type mice. Dp427 isoforms were differentially expressed in the adult brain, with Dp427c enriched in the cortex, Dp427p1/p2 in the cerebellum, and Dp427m was also detected across specific brain regions. Dp140 was expressed at lower levels than Dp427; Dp71 was the most abundant isoform in adulthood. Dp140 and Dp71 displayed dynamic developmental changes, from E15 to P60, suggesting stage-specific roles. We also analysed mdx^5cv mice lacking Dp427 and mdx52 mice lacking both Dp427 and Dp140. Both models had minimal Dp427 transcript levels, likely due to the nonsense-mediated decay, and neither expressed Dp427 protein. As expected, mdx52 mice lacked Dp140, confirming their genotypic relevance to human DMD. Our study provides the first atlas of dystrophin expression in the wild-type mouse brain, aiding understanding of the anatomical basis of behavioural and cognitive comorbidities in DMD. Full article

Background/Objectives: Carotenoids in citrus are vital nutritional compounds and precursors of the stress hormone abscisic acid (ABA). SNF1-related kinases (SnRKs)—key regulators of plant stress signaling that phosphorylate is targeting proteins for post-transcriptional regulation—mediate ABA signaling through its subfamily SnRK2-phosphatase type-2C (PP2C)-PYR1-LIKE (PYL) cascades. This study aims to identify the SnRK-PP2C-PYL family members and decipher their underlying post-transcriptional regulatory mechanisms which control carotenoid metabolism in Citrus sinensis for improved nutrition and stress resilience. Methods: SnRK, PP2C, and PYL were identified by integrated HMMER-blastp-CDD pipeline in the Citrus genome. Using two carotenoid-divergent cultivars, ‘Newhall’ (yellow) and ‘Cara Cara’ (red, hyperaccumulating linear carotenoids), we conducted spatiotemporal expression profiling and integrated transcriptomic and metabolomic data via Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules correlated with accumulation. Results: We identified 26 CsSnRKs (1 SnRK1, 7 SnRK2, 18 SnRK3), 57 CsPP2Cs, and 7 CsPYLs in Citrus sinensis. Despite a >26-fold difference in linear carotenoids, structural gene expression was similar among cultivars, strongly implicating post-transcriptional control. WGCNA identified a key turquoise module highly correlated with linear carotenoid content. This module contained phosphorylation-related genes (CsSnRK1/3.5/3.6/3.16, CsPP2C14/15/33/35/38/40/43/56, and CsPYL6), biosynthetic genes (CsPSY1, CsZISO, and CsZDS), and candidate transcription factors. Network analysis predicted that CsSnRKs, CsPP2Cs, and CsPYLs regulate phytoene-derived carotenoid biosynthesis. Conclusions: We propose a novel phosphorylation-mediated post-transcriptional regulatory network in carotenoid accumulation. This mechanism bridges ABA signaling and metabolic adaptation, providing crucial molecular targets for engineering nutrient-dense and climate-resilient citrus varieties. Full article

Background: Centrosome amplification, a hallmark of cell cycle dysregulation, drives carcinogenesis through aneuploidy induction and invasive phenotype acquisition. In pancreatic adenocarcinoma—a malignancy characterized by profound genomic instability—the molecular circuitry of centrosome amplification remains enigmatic. Critical gaps persist in understanding its spatiotemporal dynamics in tumor microenvironment remodeling and therapy resistance. Methods: This study integrated centrosome amplification-related genes from TCGA and Genecards, established a prognostic risk model through univariate Cox regression–LASSO penalized Cox regression–multivariate Cox regression analyses, and validated it using GEO datasets. Single-cell sequencing analyses dissected transcriptional heterogeneity and intercellular communication networks, while spatially resolved transcriptomics unveiled spatiotemporal expression patterns and molecular regulatory mechanisms of core genes. With further experimental validation via PCR analysis of patient-derived tissue samples confirming key gene expression patterns. Results: This study identified 23 centrosome amplification-related prognostic genes in pancreatic adenocarcinoma, establishing IFI27, KIF20A, KLK10, SPINK7, and TOP2A as highly specific diagnostic and prognostic biomarkers. The constructed signature was established as an independent prognostic indicator correlating with aggressive clinicopathological characteristics and chemoresistance. Mechanistically linked to enhanced DNA repair capacity and accelerated cell cycle progression, also synergizes with KRAS mutational profiles. Tumor microenvironment analysis revealed significant associations with immunosuppressive. Single-cell resolution demonstrated cellular specificity of IFI27/KLK10 in ductal epithelial cells and fibroblasts, with intercellular communication networks exhibiting multidimensional regulatory features. Spatially resolved transcriptomics delineated tumor-region-specific expression patterns of core genes. While PCR validation on matched tumor/normal tissues confirmed significant differential expression of IFI27, KIF20A, KLK10, and TOP2A. Conclusions: This study deciphers the multidimensional clinic–molecular network orchestrated by centrosome amplification in PDAC, revealing its dual-pathogenic mechanism in fueling tumor aggressiveness through coordinated induction of genomic instability and immunosuppressive microenvironment reprogramming. These findings establish a translational framework for developing centrosome dynamics-based prognostic stratification and molecularly targeted therapeutic strategies. Full article

The invertebrate neuropeptide F (NPF) signaling plays versatile roles in diverse biological activities and processes. Still, whether and how it mediates feeding and digestion in Pomacea canaliculate remain gaps in our knowledge. Herein, we first identified and characterized PcNPFR via bioinformatics analysis in P. canaliculate, which is a polyphagous herbivore with a voracious appetite that causes devastating damages to ecosystem functioning and services in colonized ranges. Double stranded RNA (dsRNA)-based RNA interference (RNAi) and exogenous rescue were utilized to decipher and substantiate underlying mechanisms whereby NPFR executed its modulatory functions. Multiple sequence alignment and phylogeny indicated that PcNPFR harbored typical seven transmembrane domains (7 TMD) and belonged to rhodopsin-like GPCRs, with amino acid sequence sharing 27.61–63.75% homology to orthologues. Spatio-temporal expression profiles revealed the lowest abundance of PcNPFR occurred in pleopod tissues and the egg stage, while it peaked in male snails and testes. Quantitative real-time PCR (qRT-PCR) analysis showed that 4 µg dsNPFR and 10⁻⁶ M trNPF (NPFR agonist) were optimal doses to exert silencing and rescue effects, accordingly with sampling time at 3 days post treatments. Moreover, the dsNPFR injection (4 µg) at 1/3/5/7 day/s delivered silencing efficiency of 32.20–74.01%. After 3 days upon dsNPFR knockdown (4 µg), mRNA levels of ILP7/InR/Akt/PI3Kc/PI3K_R were significantly downregulated compared to dsGFP controls, except FOXO substantially upregulated at both transcript and translation levels. In addition, the activities of alpha-amylase, protease and lipase were significantly suppressed, accompanied by decreased leaf area consumption, attenuated feeding behavior and diminished feeding rate. Moreover, expression trends were opposite and proxies were partially or fully restored to baseline levels post exogenous compensation of trNPF, suggesting phenotypes specifically attributable to PcNPFR RNAi but not off-target effects. PcNPFR is implicated in both feeding and digestion by modulating the ISP pathway and digestive enzyme activities. It may serve as a promising molecular target for RNAi-based antifeedants to manage P. canaliculate invasion. Full article

Micro-expressions, characterized by brief and subtle facial muscle movements, are essential for conveying nuanced emotions in digital humans, yet existing rendering techniques often produce rigid or emotionally monotonous animations due to the inadequate modeling of temporal dynamics and action unit interdependencies. This paper proposes a graph-driven framework for micro-expression rendering that generates emotionally diverse and lifelike expressions. We employ a 3D-ResNet-18 backbone network to perform joint spatio-temporal feature extraction from facial video sequences, enhancing sensitivity to transient motion cues. Action units (AUs) are modeled as nodes in a symmetric graph, with edge weights derived from empirical co-occurrence probabilities and processed via a graph convolutional network to capture structural dependencies and symmetric interactions. This symmetry is justified by the inherent bilateral nature of human facial anatomy, where AU relationships are based on co-occurrence and facial anatomy analysis (as per the FACS), which are typically undirected and symmetric. Human faces are symmetric, and such relationships align with the design of classic spectral GCNs for undirected graphs, assuming that adjacency matrices are symmetric to model non-directional co-occurrences effectively. Predicted AU activations and timestamps are interpolated into continuous motion curves using B-spline functions and mapped to skeletal controls within a real-time animation pipeline (Unreal Engine). Experiments on the CASME II dataset demonstrate superior performance, achieving an F1-score of 77.93% and an accuracy of 84.80% (k-fold cross-validation, k = 5), outperforming baselines in temporal segmentation. Subjective evaluations confirm that the rendered digital human exhibits improvements in perceptual clarity, naturalness, and realism. This approach bridges micro-expression recognition and high-fidelity facial animation, enabling more expressive virtual interactions through curve extraction from AU values and timestamps. Full article

Lung development is governed by tightly regulated signaling mechanisms, including endocytosis-mediated pathways critical for epithelial–mesenchymal communication and tissue remodeling. This study investigated the effects of Dab1 deficiency on the expression of endocytic and signaling-related proteins, Megalin, Cubilin, Caveolin-1, GIPC1, and Dab2IP, during embryonic lung development in yotari mice. Using immunofluorescence and quantitative image analysis, protein expressions were compared between yotari and wild-type embryos at gestational days E13.5 and E15.5. Results showed significantly reduced expression of Caveolin-1 in the yotari epithelium across both stages, along with diminished mesenchymal levels of Megalin and GIPC1 at E13.5. Cubilin and Dab2IP expression patterns showed no statistically significant differences, although developmental and compartmental shifts were observed. These findings suggest that Dab1 deficiency selectively disrupts endocytic and signaling scaffolds crucial for branching morphogenesis and alveolar maturation. The altered spatiotemporal expression of these proteins underscores the essential role of Dab1 in regulating lung epithelial–mesenchymal dynamics and maintaining developmental homeostasis during critical stages of organogenesis. Full article

The brown planthopper, Nilaparvata lugens, a major rice pest, harbors yeast-like symbionts (YLSs) that form mutualistic relationships with the host, significantly influencing its development and reproduction. As proteasome subunits play major roles in the assembly and functional maintenance of the proteasome, but their regulation on the YLSs in N. lugens are unclear. In this study, we analyzed the spatiotemporal and temporal expression patterns of five N. lugens proteasome subunits (NlPSMA2, NlPSMB5, NlPSMC4, NlPSMD10, NlPSMD13), and further verified their functions on the transovarial transmission of YLSs, in addition to the reproduction of N. lugens, based on RNA interference (RNAi). The results showed that NlPSMA2, NlPSMB5, NlPSMC4, NlPSMD10, and NlPSMD13 were highly expressed in ovarian follicular cells of N. lugens upon sexual maturation. After suppressing the expression of these genes by RNAi, N. lugens exhibited a shortened lifespan, abnormal pear-shaped follicles, and impaired oviposition capacity, but the number of YLSs in the whole body and the oocyte of N. lugens were significantly increased. These results indicate that the proteasome subunits play crucial roles in the reproduction of N. lugens and the transovarial transmission of its YLSs. Full article

Plant heat shock proteins (Hsps) are from a diverse and ancient protein family, with small Hsps of ~20 kDa molecular weight classified as Hsp20s. As a key transcription factor in the jasmonic acid (JA) pathway, myelocytomatosis protein 2 (MYC2) plays a vital role in stamen development. In this study, we identified six genes with significantly altered expression levels using previous RNA-Seq data from PhMYC2a-overexpressing and methyl jasmonate (MeJA)-treated petunia. Interestingly, five of these are Hsp20 family members (PhHsp16.0A, PhHsp16.1, PhHsp16.8, PhHsp21.9, and PhHsp40.8). Yeast one-hybrid (Y1H) and dual-luciferase assays demonstrated that PhMYC2a directly binds their promoters, indicating a collective effect. Thus, a genome-wide analysis was conducted and a total of 38 genes encoding Hsp20s were identified in the reference genome of Petunia axillaris. Phylogenetic analysis revealed that 38 members of Hsp20s were irregularly distributed on 34 chromosome scaffolds and separated into 13 subfamilies, with only PaHsp16.0A and 16.1, among the five selected Hsp20s, being in the same Cytosol IV (CIV) subfamily. Conserved motif analysis suggested that the PaHsp20 gene family members may have a high degree of conservation. The promoter sequence analysis suggested that the promoter regions of PaHsp20 genes contained multiple light- and hormone-related cis-regulatory elements. Subsequently, spatiotemporal expression patterns, analyzed by qRT-PCR, showed that PhHsp16.0A and PhHsp16.1 had relatively high expression levels in flowers, with similar expression patterns at various stages of flower bud and anther development. Furthermore, virus-induced gene silencing (VIGS) of PhHsp16.0A and PhHsp16.1 resulted in significantly reduced pollen fertility, indicating their regulation in the process of flower development and echoing the role of PhMYC2a. This study highlights the pivotal role of Hsp20s in MYC2a-mediated regulatory mechanisms during petunia pollen development. Full article

There is voluminous literature concerning the scope of topological relations that span various embedding spaces from ${\mathbb{R}}^1$ to ${\mathbb{R}}^2$, ${\mathbb{Z}}^2$ , ${\mathbb{S}}^1$ and ${\mathbb{S}}^2$ , and ${\mathbb{T}}^2$. In the case of the ${*}^1$ spaces, those relations have been considered as conceptualizations of both spatial relations and temporal relations. Missing from that list are the set of digital relations that exist within ${\mathbb{Z}}^1$ , representing discretized time, discretized ordered line segments, or discretized linear features as embedding spaces. Discretized time plays an essential role in timeseries data, spatio-temporal information systems, and geo-foundation models where time is represented in layers of consecutive spatial rasters and/or spatial vector objects colloquially referred to as space–time cubes or spatio-temporal stacks. This paper explores the digital relations that exist in ${\mathbb{Z}}^1$ interpreted as a regular topological space under the digital Jordan curve model as well as a folded-over temporal interpretation of that space for use in spatio-temporal information systems and geo-foundation models. The digital Jordan curve model represents the maximum expressive power between discretized objects, making it the ideal paradigm for a decision support system model. It identifies 34 9-intersection relations in ${\mathbb{Z}}^1$ , 42 9-intersection + margin relations in ${\mathbb{Z}}^1$ , and 74 temporal relations in ${\mathbb{Z}}^1$ , utilizing the 9+-intersection, the commercial standard for spatial information systems for querying topological relations. This work creates opportunities for better spatio-temporal reasoning capacity within spatio-temporal stacks and a more direct interface with intuitive language concepts, instrumental for effective utilization of spatial tools. Three use cases are demonstrated in the discussion, representing each of the utilities of ${\mathbb{Z}}^1$ within the spatial data science community. Full article

Soluble sugars, primarily fructose, glucose, sucrose, and sorbitol, are crucial determinants of fruit flavor and quality. As a core component of biological metabolism, sugar metabolism provides energy and carbon for fruit development, ultimately governing carbohydrate accumulation in mature fruits. This process requires the coordinated activities of multiple enzymes and transporters, modulated by the spatiotemporal expression patterns of their encoding genes. Therefore, it is essential to elucidate both the activities of these enzymes across different fruits and their underlying gene expression patterns. While significant progress has been made in functional genes involved in soluble sugar metabolism and deciphering their regulatory networks, an overall introduction of this knowledge remains lacking. This review presents an integrative analysis of soluble sugar accumulation during fruit development, encompassing spatiotemporal dynamics of key metabolic enzymes, functional characterization of encoding genes, signaling response mechanisms governing gene regulation, and the overarching genetic network. Full article