Search Results (15,670)

Collagen VI is an extracellular matrix component encoded by COL6A1, COL6A2 and COL6A3 genes. Causative variants in these genes are associated with the following collagen VI-related myopathies: severe Ullrich congenital muscular dystrophy (UCMD), milder Bethlem myopathy (BM) and intermediate phenotypes (INT). We report the mutation landscape of COL6A genes in 138 Italian patients affected with a collagen VI-related phenotype. The patient cohort included 44 (32%) UCMD, 9 (7%) INT, 61 (44%) BM and 21 (15%) INT/BM patients; 3 patients (2%) with a myosclerosis myopathy (MM) phenotype were also considered. We identified 104 different variants: 26 in COL6A1 (25%), 52 in COL6A2 (50%) and 26 in COL6A3 (25%). The variant spectrum includes missense, splicing, small indel, frameshifting and nonsense variants. Glycine substitutions in the triple helical domain of the collagen VI protein are the commonest variants and occur in all phenotypes. Our genetic profiling disclosed a unique mutation scenario and phenotypic association of the COL6A2 gene with respect to COL6A1 and COL6A3, which may be related to a different evolutive history. Landscape mutation analysis of variants occurring in ultrarare conditions, such as collagen VI-related myopathies, is crucial to better understand the variations’ profile and to gain insight into fundamental knowledge about gene structure and its evolutive origin. Full article

DNA binding proteins play a crucial role in regulating gene expression, DNA replication, and chromatin organization. While many DNA-binding proteins have been identified, many unique DNA-binding proteins in non-model organisms and recently evolved lineage- or species-specific proteins remain uncharacterized or often lack experimental validation. In addition, genetic variants may alter previously known DNA-binding proteins, leading to loss of binding ability. To address this gap, various computational tools have been developed to predict DNA-binding proteins from protein sequences or structures. Yet, their real-world utility in biological research remains uncertain. To evaluate their effectiveness, we assessed the availability and predictive performance of existing tools using five real-world case studies. We found that most tools were web-based, offering accessibility to researchers without computational expertise. However, many suffered from poor maintenance, including frequent server connection problems, input errors, and long processing times. Among the ten tools that were functional and practical, we found that prediction scores often failed to reflect incorrect outputs, and multiple methods frequently produced the same erroneous predictions. Overall, even a small number of misclassifications can significantly distort biological interpretation, indicating that current DNA-binding prediction tools are not yet sufficiently reliable for empirical research. Full article

Glioblastoma multiforme (GBM) is an aggressive brain cancer characterized by highly invasive growth driven by glial-mesenchymal transition (GMT). Given the urgent need for effective therapies targeting this process, we aimed to discover potential GMT inhibitors using transcriptomic-based repurposing applied to both approved and experimental drugs. Deep bioinformatic analysis of transcriptomic data from GBM patient tumors and GBM cell lines with mesenchymal phenotype using gene set variation analysis (GSVA), weighted gene co-expression network analysis (WGCNA), reconstruction of GMT-related gene association networks, gene set enrichment analysis (GSEA), and the search for correlation with transcriptomic profiles of known GMT markers, revealed a novel 31-gene GMT signature applicable as relevant input data for the connectivity map-based drug repurposing study. Using this gene signature, a number of small-molecule compounds were predicted as potent anti-GMT agents. Further ranking according to their blood–brain barrier permeability, as well as structural and transcriptomic similarities to known anti-GBM drugs, revealed SP600125, vemurafenib, FG-7142, dibenzoylmethane, and phensuximide as the most promising for GMT inhibition. In vitro validation showed that SP600125, which is most closely associated with GMT-related hub genes, effectively inhibited TGF-β1- and chemical hypoxia-induced GMT in U87 GBM cells by reducing morphological changes, migration, vasculogenic mimicry, and mesenchymal marker expression. These results clearly demonstrate the applicability of connectivity mapping as a powerful tool to accelerate the discovery of effective GMT-targeting therapies for GBM and significantly expand our understanding of the antitumor potential of SP600125. Full article

The investigation and comparison of chloroplast genomes facilitate our deeper elucidation of the evolutionary dynamics and phylogenetics of plant species, particularly non-model plants. Opisthopappus is a genus of Asteraceae that is endemic to the Taihang Mountains in China, which includes Opisthopappus taihangensis and Opisthopappus longilobus. Although certain chloroplast genomic data are available, the comprehensive evolutionary relationships of chloroplast genomes in this genus are not yet fully understood. In this study, the assembled O. taihangensis chloroplast genomes exhibited a quadripartite structure with 131 genes, encompassing 86 protein-coding, 37 tRNA, and eight rRNA genes. The basic phylogenetic relationships of 275 Asteraceae species were consistent with preceding studies. Opisthopappus with Ajania and Chrysanthemum were gathered together in Trib. Anthemideae. However, O. taihangensis and O. longilobus were not clustered into a group. Six and eight variable hotspots were detected in Opisthopappus and Asteraceae respectively. A total of 18 optimal codons were identified in two species. Differentiation in codon usage patterns was primarily influenced by natural selection between O. taihangensis and O. longilobus. Thereinto, GCU (Ala) was specific to O. taihangensis, while ACU (Thr) was to O. longilobus. Most of the codons preferentially ended with A/U, with only two genes (rpl16 and matK) being subjected to positive selection in Opisthopappus. Under salt stress, 25 editing sites were detected in O. longilobus, and 34 editing sites were found in O. taihangensis. All editing sites were C to U transitions. Distinct editing events occurred in the two species. During the evolution of chloroplast genomes, the genes that undergo positive selection may help two Opisthopappus species to adapt the harsh cliff environment of the Taihang Mountains and ensure their normal growth and development. In response to stress, O. taihangensis and O. longilobus tended to utilize different codons and initiate unique RNA editing events. These will facilitate further work on taxonomy, phylogenetics, and adaptive evolution of Opisthopappus, even Anthemideae or Asteraceae. Full article

The SQUAMOSA promoter-binding protein-like (SPL/SBP) family plays crucial roles in multiple developmental processes. Phalaenopsis equestris is a key ornamental and breeding species known for producing abundant colorful flowers on a single inflorescence. The SPL gene family in this species remains largely uncharacterized. In this study, 15 SPL genes were identified, all encoding proteins that are bioinformatically predicted to be nuclear-localized, hydrophilic, and unstable, with conserved SBP domains. Phylogenetic and collinearity analyses revealed a closer evolutionary relationship with rice SPLs than Arabidopsis SPLs. Conserved motif and gene structure analyses showed that subfamily II members possess more motifs and introns, implying functional complexity. Five PeqSPLs contained transmembrane domains, suggesting potential dual nuclear/cytoplasmic roles. Promoter analysis revealed abundant cis-elements responsive to light, stress, and phytohormones. Expression profiling across tissues showed that PeqSPL2, PeqSPL3, and PeqSPL5 exhibited broad expression and PeqSPL10 exhibited predominantly high expression in flowers, indicating possible roles in normal growth and floral development. This study provides a foundation for further functional exploration of PeqSPL genes in P. equestris. Full article

Bacterial microcompartments (BMCs) are intracellular structures for compartmentalizing specific metabolic pathways in bacteria. As a unique type of BMCs, carboxysomes utilize protein shells to sequester ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase for efficient carbon dioxide (CO₂) fixation. This study aims to reconstruct an α-carboxysome in Saccharomyces cerevisiae and investigate its metabolic effects. Here, genes of the cso operon from Halothiobacillus neapolitanus, Calvin cycle-related enzyme phosphoribulokinase (PRK) from Spinacia oleracea, and two S. cerevisiae chaperone genes, HSP60 and HSP10, were introduced into S. cerevisiae. The engineered yeast strain demonstrated assembled and enzymatically active Rubisco, significant increase in ethanol production and reduction in the byproduct glycerol. Formation of the α-carboxysome structures was observed after purification by sucrose density gradient centrifugation. The engineered yeast strain harboring functional α-carboxysome has the potential for enhancing bioethanol production. Full article

Bacteriophages have been widely investigated as a promising treatment of food, medical equipment, and humans colonized by antibiotic-resistant bacteria. Phages pose particular interest in combating those bacteria which form biofilms, such as the medically important human pathogen Pseudomonas aeruginosa and several plant pathogens, including P. syringae. In an undergraduate lab course, P. putida was used as the host to isolate novel anti-pseudomonal bacteriophages. Environmental samples of soil and water were collected, and purified phage isolates were obtained. After Illumina sequencing, genomes of these phages were assembled de novo and annotated. Assembled genomes were compared with known genomes in the literature and GenBank to identify taxonomic relations and to refine their functional annotations. The thirteen phages described are sipho-, myo-, and podoviruses in several families of Caudoviricetes, spanning several novel genera, with genomes ranging from 40,000 to 96,000 bp. One phage (DDSR119) is unique and is the first reported P. putida siphovirus. The remaining 12 can be clustered into four distinct groups. Six are highly related to each other and to previously described Autotranscriptaviridae phages: Waldo5, PlaquesPlease, and Laces98 all belong to the Waldovirus genus, whereas Stalingrad, Bosely, and Stamos belong to the Troedvirus genus. Zuri was previously classified as the founding member of a new genus Zurivirus within the family Schitoviridae. Ebordelon and Holyagarpour each represent different species within Zurivirus, whereas Meara is a more distantly related member of the Schitoviridae. Dolphis and Jeremy are similar enough to form a genus but have only a few distant relatives among sequenced phages and are notable for being temperate. We identified the lysis cassettes in all 13 phages, compared tail spike structures, and found auxiliary metabolic genes in several. Studies like these, which isolate and characterize infectious virions, enable the identification of novel proteins and molecular systems and also provide the raw materials for further study, evaluation, and manipulation of phage proteins and their hosts. Full article

Protein palmitoylation, a key post-translational modification (PTM) regulating protein transport and function, is catalyzed by palmitoyl transferases (PATs). PATs play vital roles in plant growth, development, and stress responses, yet their characterization in citrus remains limited. This study identified 23 PAT genes (CitPATs) possessing the conserved DHHC domain in the citrus genome through comprehensive genome-wide analysis. Analysis revealed that most CitPAT proteins are hydrophilic, basic, and stable, with significant variations in sequence length. Gene structure and motif analysis confirmed 10 conserved motifs, with the DHHC domain being the most conserved among all 23 members. The CitPAT genes were unevenly distributed across nine chromosomes and exhibit high evolutionary conservation. Promoter analysis identified numerous cis-acting elements associated with abiotic stress and hormone responses, including basic regulatory elements, light-responsive elements, and stress-responsive elements, with light-responsive elements being predominant. Expression profiling during fruit development revealed distinct correlation patterns with citric acid dynamics: CitPAT6, CitPAT18, and CitPAT23 showed positive correlations with acid accumulation, while CitPAT1, CitPAT10, and CitPAT13 exhibited negative correlations. Further RT-qPCR experiments revealed that CitPAT1 and CitPAT10 consistently demonstrated strong negative correlations with citrate content throughout fruit development. This functional diversification suggests roles in regulating citric acid metabolism. These findings provide novel insights into quality formation in facility-cultivated citrus and establish a foundation for understanding PAT-mediated regulation of fruit development. Full article

Mikania micrantha, commonly known as mile-a-minute weed, is listed among the world’s top 10 worst weeds. Although native to humid regions of South America, it has recently been found to colonize arid habitats as well. Despite pronounced seasonal hydroclimatic variations in South China and increasing drought due to global climate change, the mechanisms underlying M. micrantha’s drought tolerance remain poorly understood. In this study, we compared the photosynthetic responses of M. micrantha leaves and stems between the dry (June) and wet (December) seasons through field experiments. We measured changes in phenotype, photosynthetic characteristics, and the content of antioxidant and osmotic adjustment substances, using the co-occurring native vine Paederia scandens as a control. The results revealed that during the dry season, M. micrantha leaves exhibited wilting, along with significant reductions in relative water content (RWC), chlorophyll (Chl), soluble sugar (SS), and soluble protein (SP). In contrast, the stems of M. micrantha maintained relatively stable phenotypes and chlorophyll levels compared to those of P. scandens. Notably, M. micrantha stems exhibited significant increases in vessel wall thickness, vessel density, total phenol content, and the activities of peroxidase (POD) and ascorbate peroxidase (APX). Furthermore, compared to P. scandens, M. micrantha stems displayed a greater increase in cortex proportion, flavonoid content, and soluble protein content. Expression analysis of bZIP transcription factors further revealed drought-responsive upregulation of specific genes (bZIP60, ZIP42-1), suggesting their potential involvement in drought response. These results indicate that although the leaves of M. micrantha are susceptible to prolonged drought, the stems exhibit considerable resilience, which may be attributed to a combination of traits including structural modifications in stem anatomy, enhanced antioxidant capacity, and osmotic adjustment. These insights suggest that stem-specific adaptations are key to its drought tolerance, providing a theoretical foundation for understanding the habitat distribution of M. micrantha and informing effective management strategies. Full article

Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous and vascular systems, as well as facial and cranial structures. Paradoxically, the syndrome manifests with greater severity in heterozygous females, whereas hemizygous males typically present with mild or no abnormalities. Methods and Results: We report the case of a late preterm female neonate with dysmorphic features at birth, who subsequently developed necrotizing enterocolitis (NEC) caused by thrombosis of the superior mesenteric artery. Extensive bowel resection led to short bowel syndrome, resulting in cholestatic liver disease, malabsorption, and growth impairment. Array-comparative genomic hybridization (a-CGH) analysis identified a ~791 Kb microduplication at Xq13.1, encompassing the EFNB1 gene, confirming the diagnosis of CFND. She was enrolled in a multidisciplinary follow-up program and, at 2 years of age, presents with marked growth and neurodevelopmental delay. Conclusions: This report describes a rare association between CFND and NEC caused by superior mesenteric artery thrombosis. To the best of our knowledge, no previously reported cases of CFND associated with thrombosis or thrombosis-related conditions, including NEC, have been identified. This is based on a literature review (2004–2025) performed using PubMed and Scopus, and limited to English-language case reports and reviews. Full article

Recent developments in next-generation sequencing technology have led to the creation of extensive, open-source protein databases consisting of hundreds of millions of sequences. To render these sequences applicable in biomedical applications, they must be meticulously annotated by wet lab testing or extracting them from existing literature. Over the last few years, researchers have developed numerous automatic annotation systems, particularly deep learning models based on machine learning and artificial intelligence, to address this issue. In this work, we propose a transformer-based fusion model capable of predicting Gene Ontology (GO) terms from full-scale protein sequences, achieving state-of-the-art accuracy compared to other contemporary machine learning annotation systems. The approach performs particularly well on clustered split datasets, which comprise training and testing samples originating from distinct distributions that are structurally diverse. This demonstrates that the model is able to understand both short and long term dependencies within the protein’s structure and can capture sequence features that are predictive of the various GO terms. Furthermore, the technique is lightweight and less computationally expensive compared to the benchmark methods, while at the same time unaffected by sequence length, rendering it appropriate for diverse applications with varying sequence lengths. Full article

Francisella tularensis is a pathogenic bacterium and the causative agent of the disease tularemia. Because of the virulence of this bacterium and the potential for weaponization, the Centers for Disease Control and Prevention (CDC) has classified F. tularensis as a Category A Bioterrorism Agent. Therefore, the need for new treatments for tularemia is critical. In this work, we screened a cataloged library of natural extracts to identify those that inhibit the growth of F. tularensis only during infection of THP-1 monocyte cells. One of the most promising extracts identified in this screen was derived from Foeniculum vulgare (fennel). Using bioassay-guided fractionation, the fennel extract was fractionated, and the bioactive compound was isolated and structurally elucidated as the phenylpropanoid dillapiole. We subsequently confirmed that dillapiole alone could limit the replication of F. tularensis in infected THP-1 cells, but not outside of this infection model. Investigations on host responses suggested that dillapiole was not substantially augmenting the immunity of these THP-1 cells. We then investigated the potential virulence modulation activity of dillapiole. To test this hypothesis, RNA-seq analysis was carried out on F. tularensis bacteria that were treated with dillapiole. This showed that dillapiole caused a significant downregulation of genes controlled by the transcriptional regulators MglA and SspA, including those encoded in the Francisella pathogenicity island. Western blotting validated these findings as both IglA and IglC expression was diminished in F. tularensis LVS bacteria treated with dillapiole. Because dillapiole dampens the virulence gene expression of F. tularensis, we concluded that this compound has potential to be used as a novel therapeutic for tularemia with a unique mechanism of action. Full article

Background: Personalizing adjuvant chemotherapy (ACT) after curative resection in early-stage NSCLC remains unmet because prior ACT-biomarker findings rarely reproduce across studies. Key barriers are platform and preprocessing heterogeneity, dominant batch effects, and incomplete ACT annotations. As a result, many signatures that perform well in a single cohort fail during external validation. We created an open, harmonized meta-database linking gene expression with curated ACT exposure and survival to enable fair benchmarking and modeling. Methods: A PRISMA-guided search of 999 GEO studies (through January 2025) used LLM-assisted triage of titles, clinical tables, and free text to identify datasets with explicit ACT status and patient-level survival. Eight Affymetrix microarray cohorts (GPL570/GPL96) met eligibility. Raw CEL files underwent robust multi-array average; probes were re-annotated to Entrez IDs and collapsed by median. Covariate-preserving ComBat adjusted platform/study while retaining several clinical factors. Batch structure was quantified by principal-component analysis (PCA) variance, silhouette width, and UMAP. Two quality-control (QC) filters, median M-score deviation and PCA leverage, flagged and removed technical outliers. Results: The final meta-database comprises 1340 patients (223 (16.6%) ACT; 1117 (83.4%) observation), 13,039 intersecting genes, and 594 overall-survival events. Batch-associated variance (PC1 + PC2) decreased from 63.1% to 20.1%, and mean silhouette width shifted from 0.82 to −0.19 post-correction. Seven arrays (0.5%) were excluded by QC. Event depth supports high-dimensional survival and heterogeneity-of-treatment modeling, and the multi-cohort design enables internal–external validation. Conclusions: This first open, rigorously harmonized NSCLC transcriptomic database provides the sample size, demographic diversity, and technical consistency required to benchmark ACT-benefit markers. By making these data openly available, it will accelerate equitable precision-oncology research and enable data-driven treatment decisions in early-stage NSCLC. Full article

Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms—such as DNA methylation and histone modification—in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability. Full article

Carrot (Daucus carota L.) is an important root vegetable crop in the Apiaceae and is widely cultivated around the world. Expansins play crucial roles in the growth and development of plants. Here, a total of 35 carrot expansins were identified from carrot. Sequence alignment and phylogenetic analysis revealed that carrot expansins could be classified into four subfamilies, each with similar exon/intron structures and motif compositions, indicating that carrot expansins were relatively conserved during evolution. Chromosomal localization and gene duplication analysis indicated that DcEXP genes were unevenly distributed across carrot nine chromosomes and had evolved predominantly under purifying selection. Measurements of key agronomic characters of carrots at different developmental stages (30, 60, and 90 days after sowing) indicated significant positive correlations among root fresh weight, aboveground fresh weight, root–shoot ratio, root length, and root diameter. The period from 30 to 60 days after sowing was identified as the primary phase of taproot enlargement. Analysis of spatiotemporal expression patterns revealed that most DcEXP genes were specifically expressed in the taproots, and only one gene, DcEXP18, was specifically expressed in leaves. During the rapid growth period of carrot taproots (30 and 60 days after sowing), the genes DcEXP2, DcEXP3, DcEXP5, DcEXP8, DcEXP11, DcEXP13, DcEXP17, DcEXP19, DcEXP20, DcEXP22, DcEXP26, DcEXP28, and DcEXP33 exhibited high expression levels, suggesting that they played potential important roles in carrot taproot enlargement. These findings will advance our knowledge of the molecular mechanisms underlying expansin regulation of carrot growth and development. Full article