Search Results (20,313)

Background: Vancomycin-resistant Enterococcus faecium (VREfm), particularly vanA-positive strains, represents a growing threat in hospital settings worldwide. These bacteria are able to survive under severe environmental conditions, including high temperatures and saline concentrations. High genome plasticity and advanced ability of inheriting antimicrobial resistance determinants defined the success of E. faecium as a hospital pathogen. Methods: This study presents the whole genomic characterization of vanA-positive VREfm isolates, analyzing 10 clinical isolates collected from three tertiary care hospitals in Moscow, Russia. Several typing approaches, including two MLST schemes and cgMLST profiles, were used to elucidate the relationship between the isolates. Phylogenetic analysis placed the isolates in context with global VREfm populations, demonstrating both local clonal expansion and possible international connections. Phenotypic and genomic antimicrobial resistance profiles were obtained, as well as data regarding the repertoire of virulence factors and plasmid content. Results: Whole genome sequencing revealed that all isolates belonged to the clinically significant CC17 lineage, specifically sequence types ST80 and ST552. Notably, two isolates possessed truncated Tn1546-type transposons lacking vanY and vanZ genes, representing a potentially emerging variant of the vanA operon in Russian clinical settings. A plasmid carrying a truncated vanA operon was reconstructed using long-read sequencing. Conclusions: The study highlights the utility of genomic investigation for tracking resistance mechanisms and strain dissemination, providing crucial baseline data for epidemiological surveillance of infections caused by VREfm in Russia. These findings emphasize the need for continued genomic monitoring to understand the evolution and spread of antimicrobial resistance in clinically important enterococcal lineages. Full article

Floccularia luteovirens is a valuable medicinal and edible ectomycorrhizal fungus that is endemic to alpine meadows on the Qinghai–Tibet Plateau. It is of significant ecological and pharmacological importance. To overcome the genomic limitations of previous fragmented assemblies, we present the first haplotype-phased, chromosome-scale genome of the Qinghai-derived QHU-1 strain using an integrated approach of PacBio HiFi, Hi-C, and Illumina sequencing. The high-contiguity assembly spans 13 chromosomes with 97.6% BUSCO completeness. Phylogenomic analysis of 31 basidiomycetes clarified a historical misclassification by placing F. luteovirens closest to Mycocalia denudata/Crucibulum laeve, thus confirming its distinct lineage from Armillaria spp. through low synteny and divergent gene family dynamics. Analyses of adaptive evolution revealed strong purifying selection and stable transposable elements, suggesting genomic adaptations to extreme UV/cold stress. AntiSMASH identified 15 biosynthetic gene clusters (BGCs), which encode diverse terpenoids (7), NRPS-like enzymes (4), PKSs (2), and a hybrid synthase with unique KS-AT-PT-A domains, which have the potential to generate novel metabolites. This chromosome-level resource sheds light on the genetic basis of F. luteovirens’ taxonomy, alpine survival, and symbiotic functions while also unlocking its potential for bioprospecting bioactive compounds. Full article

Background/Objectives: Non-Hodgkin lymphoma (NHL) is a group of blood cancers that arise in the lymphatic nodes and other tissues after an injury to the DNA of B/T lineage and NK lymphocytes. Recently, we reported that incomptine A (IA) has in vivo antilymphoma properties. This research aimed to evaluate the effects of IA in the treatment of NHL using antilymphoma activity, Tandem Mass Tag (TMT), and bioinformatics approaches. Methods: The antilymphoma activity of IA was tested on male Balb/c mice inoculated with U-937 cells. Also, TMT, gene ontology enrichment, Reactome pathway, Kyoto Encyclopedia of Gene and Genomes pathway, molecular docking, toxicoinformatic, and pharmaceutical analyses were performed. Results: By TMT analysis of the altered levels of proteins present in the lymph nodes of Balb/c mice with NHL and treated with IA, we identified 106 significantly differentially expressed proteins (DEPs), including Il1rap, Ifi44, Timd4, Apoa4, and Fabp3 as well as Myh3, Eno 2, and H4c11. Among these, the Fhl1 result was the most important cluster altered and a potential core target of IA for the treatment of NHL. Network pharmacology studies have revealed that DEPs are associated with processes such as muscle contraction, glycolysis, hemostasis, epigenetic regulation of gene expression, transport of small molecules, neutrophil extracellular trap formation, adrenergic signaling in cardiomyocytes, systemic lupus erythematosus, alcoholism, and platelet activation, signaling, and aggregation. Computational studies revealed strong binding affinities with six proteins associated with cancer, positive pharmacokinetic properties, and no toxicity. Conclusions: Our contribution suggests that IA may be a compound with potential therapeutic effects against NHL. Full article

A class of retinal dystrophies known as retinitis pigmentosa (RP) is caused by the loss of photoreceptor cells. RP can be genetically transmitted as an autosomal dominant, autosomal recessive, or X-linked trait. About one-third of genes implicated in retinal degeneration encode for proteins whose functional dysregulation affects the “connecting cilium” in photoreceptors, altering its structure and function. Here we report on a 33-year-old woman who was referred for clinical genetic testing following a previous diagnosis of degenerative retinopathy, which was not informative. She was enrolled in a research program dedicated to undiagnosed retinal disorders, where a whole genome sequencing approach was employed to understand the underlying genetic basis. The genomic analysis documented the occurrence of compound heterozygosity for two functionally relevant missense variants in BAIAP3, which encodes a protein with a well-documented role in SNARE-mediated trafficking and ciliogenesis. Confocal microscopy analysis showed elongated cilia in patient-derived and BAIAP3-depleted fibroblasts compared to control cells. Real-time PCR analyses showed a consistent significant reduction of GLI1 mRNA levels in patient-derived and BAIAP3-depleted cells, both in basal conditions and after treatment with Smoothened agonist, SAG, indicating Sonic hedgehog signaling dysregulation. Collectively, these data suggest that biallelic loss-of-function variants of BAIAP3 may cause photoreceptor degeneration and underlie isolated RP. Full article

Background: The Space Omics and Medical Atlas (SOMA) is an extensive database containing gene expression information from samples collected during the short-duration Inspiration4 spaceflight mission in 2021. Given our prior understanding of the genetic basis for cardiovascular diseases in spaceflight, including orthostatic intolerance and cardiac deconditioning, we aimed to characterize changes in differential gene expression among astronauts using SOMA-derived data and curated cardiovascular pathways. Methods: Using the KEGG 2021 database, we curated a list of genes related to cardiovascular adaptations in spaceflight, focusing on pathways such as fluid shear stress and atherosclerosis, lipid metabolism, arrhythmogenic ventricular hypertrophy, and cardiac muscle contraction. Genes were cross-matched to spaceflight-relevant datasets from the Open Science Data Repository (OSDR). Differential expression analysis was performed using DESeq2 (v1.40.2, R) with normalization by median-of-ratios, paired pre-/post-flight covariates, and log2 fold change shrinkage using apeglm. Differentially expressed genes (DEGs) were defined as |log2FC| ≥ 1 and FDR < 0.05 (Benjamini–Hochberg correction). Module score analyses were conducted across SOMA cell types to confirm conserved cardiac adaptation genes. Results: A total of 185 spaceflight-relevant genes were analyzed. Statistically significant changes were observed in immune-related cardiovascular pathways, particularly within monocytes and T cells. Persistent upregulation of arrhythmogenic genes such as GJA1 was noted at post-flight day 82. WikiPathways enrichment revealed additional pathways, including focal adhesion, insulin signaling, and heart development. Conclusions: Short-duration spaceflight induces significant gene expression changes that are relevant to cardiovascular disease risk. These changes are mediated largely through immune signaling and transcriptional regulation in peripheral blood mononuclear cells. Findings highlight the need for tailored countermeasures and longitudinal monitoring in future long-duration missions. Full article

The Naozhou stock of large yellow croakers (Larimichthys crocea) exhibits unique phenotypic traits and high genetic diversity, making it a valuable resource for selective breeding and genetic conservation in aquaculture. Despite its importance, simple sequence repeat (SSR) markers have not been developed for this stock, which limits efforts in genetic evaluation, breeding optimization, and sustainable utilization of this commercially important species. In this study, 195,263 SSRs were identified from the genome of the Naozhou stock of large yellow croaker, covering a total length of 16,578,990 bp with a density of 288 bp/Mb. Dinucleotide repeats were the most common, with the AC motif being the most prevalent. The frequency of SSR markers ranged from 245.63 to 346.60 per Mb. A total of 30 primer pairs were synthesized, of which 28 pairs (93.3%) successfully amplified clear and reproducible bands in PCR assays. Among these, 28 SSR markers exhibited distinct and reproducible bands following gel electrophoresis. For eight SSR loci, the number of alleles (Na) ranged from 4 to 22 (mean = 11.375), while the effective number of alleles (Ne) ranged from 1.5401 to 10.4727 (mean = 5.6475). The assembled mitochondrial genome (mtDNA) was 16,467 bp in length and comprised 37 genes, including 13 protein-coding genes (PCGs), 22 tRNA genes, and 2 rRNA genes. The total sequence length of the PCGs was 11,431 bp, accounting for 69.4% of the mtDNA. A large portion of the PCGs (5) used incomplete stop codons (e.g., nad2, nad3, cox2), while others used TAA stop codons (e.g., nad6, nad5, TrnT). The mtDNA encoded a total of 3808 codons, with UAA showing the highest relative synonymous codon usage value. The SSR markers and mtDNA data generated in this study provide valuable tools for future genetic breeding and genomic research on the Naozhou stock of large yellow croakers. Full article

Biomolecular condensates (BCs), formed through liquid–liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies. Full article

This study investigated the molecular mechanisms by which phthalates induce depression, utilizing network toxicology and molecular docking techniques. By integrating the TargetNet, GeneCards, and PharmMapper databases, 658 potential target genes of phthalates were identified. Additionally, 5433 depression-related targets were retrieved from the GeneCards and OMIM databases. Comparative analysis revealed 360 common targets implicated in both phthalate action and depression. A Protein-Protein Interaction (PPI) network was constructed using the STRING database. Subsequently, the CytoHubba plugin (employing the MCC algorithm) within Cytoscape was used to screen the network, identifying the top 20 hub genes. These core genes include AKT1, CASP3, TNF, TP53, BCL2, and IL6, among others. Validation on the GEO dataset (GSE23848) revealed that the expression of multiple core genes was significantly upregulated in patients with depression (p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that phthalates mainly regulate biological processes such as extracellular stimulus response, lipopolysaccharide metabolism, and chemical synaptic transmission. Depression is mediated by the AGE-RAGE signaling pathway (a complication of diabetes), lipids and atherosclerosis, Endocrine resistance, and the PI3K-Akt signaling pathway. Molecular docking confirmed that phthalates have strong binding activity with key targets (CASP3, TNF, TP53, BCL2, IL6). These findings present a novel paradigm for evaluating the health risks posed by environmental pollutants. Full article

Polyamines (PAs), including putrescine, spermidine, spermine, and thermospermine, play essential roles in plant growth, development, and responses to stress. However, the structure and function of PA biosynthetic genes in pepper remain poorly characterized. This study aimed to identify PA biosynthesis genes in the pepper genome using bioinformatics approaches and to assess their expression under various stress conditions. A total of 16 PA biosynthesis-related genes were identified, representing members of the arginine decarboxylase (ADC), ornithine decarboxylase (ODC), agmatine iminohydrolase (AIH), N-carbamoylputrescine amidohydrolase (CPA), S-adenosylmethionine decarboxylase (SAMDC), spermidine synthase (SPDS), spermine synthase (SPMS), and ACAULIS5 (ACL5) gene families. These genes encode proteins with an average molecular weight of approximately 40 kDa, primarily localized in the mitochondria and cytoplasm. Promoter analysis revealed multiple cis-acting elements associated with stress and phytohormone responsiveness. Gene expression was induced by various abiotic stresses, including saline-alkaline, drought, heat, cold, and hydrogen peroxide, as well as by phytohormones such as abscisic acid, ethylene, salicylic acid, auxin, and gibberellin. Overall, this study provides a comprehensive analysis of PA biosynthesis genes in pepper and highlights their potential roles in stress adaptation and hormone signalling, offering a foundation for further exploration of PA-mediated stress tolerance mechanisms. Full article

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic that inhibits bacterial protein synthesis through binding to ribosomal RNA, also preventing the assembly of the initiation complex during translation. It is one of the last-line therapeutic options for serious infections caused by problematic Gram-positive pathogens, including vancomycin-resistant and multidrug-resistant Enterococcus species. Data from recent large-scale studies show a 2.5-fold increase in the prevalence of clinical LNZ-resistant enterococci (LRE) over the past decade with a global detection rate of 1.1% for LNZ-resistant E. faecium (LREfm) and 2.2% for LNZ-resistant E. faecalis (LREfs). Most reported cases have originated from China, followed by South Korea and the United States. LREfm typically belongs to the high-risk clonal complex 17, whereas LREfs demonstrates a heterogeneous population structure. Mutations in the 23S rRNA and ribosomal proteins, as well as acquired resistance genes such as cfr, optrA, and poxtA are involved in the development of LNZ resistance among enterococci. Whole-genome sequencing (WGS) has been recognized as a gold standard for identifying the underlying molecular mechanisms. It exposes that numerous LRE isolates possess multiple LNZ resistance determinants and mutations, further complicating the treatment strategies. The present review article summarizes all known mutational and non-mutational LNZ resistance mechanisms and presents a global overview of WGS-based studies with emphasis on resistome analysis of clinical LREfs and LREfm isolates published in the literature during the period 2014–2025. Full article

Carbohydrates are a primary nutrient for plant growth, and sugar transporter proteins play a crucial role in sugar allocation. In this study, hexose transporter genes encoding in the genome of colored calla lily ‘Jingcai Yangguang’ (Zantedeschia elliottiana cv. Jingcai Yangguang) were identified, and their expression patterns following infection by Pectobacterium carotovora subsp. Carotovora were investigated. Additionally, the transport characteristics of three hexose transporters, ZeSTP7, ZeSTP15, and ZeSTP17, were determined. The results showed that the sugar transporter protein family in Z. elliottiana comprises 18 members, most of which possess 12 transmembrane domains. Phylogenetic analysis revealed that the ZeSTP gene family was divided into five subgroups. Tandem gene duplication events were identified on the 16 chromosomes of Z. elliottiana, with multiple tandemly duplicated genes detected. Comparative analysis of synteny between species identified ZeSTP8 and OsSTP22 as homologous gene pairs, while OsSTP6 (OsMST6) was identified as a homologous gene pair with both ZeSTP14 and ZeSTP17. Following infection by P. carotovora subsp. carotovora, the transcript levels of ZeSTP7, ZeSTP15, and ZeST17 were all significantly elevated. Yeast mutant hexose complementation tests indicated that ZeSTP7 could transport glucose and galactose, whereas ZeSTP15 and ZeSTP17 exhibited limited transport capacity in this respect. This study provides a systematic identification and analysis of hexose transporter genes at the genome-wide level, highlighting the role of ZeSTP genes in the response of colored calla lily to soft rot and laying a theoretical foundation for further understanding the functions of sugar transporter genes. Full article

Retrotransposons exhibit increased activity in cancer cells. One possible approach to anticancer therapy is to use this activity to influence the energy balance in cells. Abnormal distribution of retrotransposons in the genome requires additional energy consumption, which can lead to a significant decrease in the total amount of free ATP molecules in the cell. A decrease in ATP levels below a certain threshold can in turn trigger a cell death program. To investigate the possibility of such a scenario, we developed a mathematical model of the cellular energy balance that describes the dynamics of energy consumption by the main cellular processes, including costs of retrotransposon activity. The model considers changes in the concentrations of ATP, active retrotransposons (LINE-1 and SINE) in the human genome, as well as mRNAs and proteins that are expression products of retrotransposon and constitutive genes. We estimated the parameter values in the model based on literature data and numerical optimization. We found a single stable stationary solution, characterized by low retrotransposon activity, and used it as the reference steady state for further analysis. Parametric sensitivity analysis revealed the parameters whose changes had the greatest impact on cellular ATP levels. The LINE-1 deactivation rate constant and the maximum LINE-1 transcription rate were the most sensitive among the transposon-related parameters. Perturbation of these parameters led to a decrease in the number of free ATP to 30% of the reference value and below. Transcription of retrotransposons under perturbed parameters became comparable to the translation of constitutive genes in terms of energy costs. The presented results indicate that cancer cell death can be initiated by increasing the load on the energy balance due to the activation of transposons. Full article

Bacterial cell morphology might result from natural selection to gain a competitive advantage under environmentally stressful conditions such as nutrient limitation. In nutrient-limited conditions, a higher surface-to-volume ratio is crucial for cell survival because it allows for a more efficient exchange of nutrients and waste products. A bacterial strain YC6860^T isolated from the rhizosphere of rice (Oryza sativa L.) showed pleomorphic behavior with smooth cell morphology and wrinkled surface rods depending upon nutritional conditions. Based on scanning and transmission electron microscopy studies, we hypothesized that the surface-to-volume ratio of cells would increase with decreasing nutrient concentrations and tested this quantitatively. The transition from smooth to wrinkled cell surface morphology could be one of the adaptation strategies by which YC6860^T maximizes its ability to access available nutrients. To characterize the properties of the wrinkled strain, we performed taxonomic and phylogenetic analyses. 16S rRNA gene sequencing results showed that the strain represented a novel, deep-rooting lineage within the order Rhizobiales with the highest similarity of 94.2% to Pseudorhodoplanes sinuspersici RIPI 110^T. Whole-genome sequencing was also performed to characterize its genetic features. The low phylogenetic and genetic similarity is probably related to the wrinkled morphology of the strain. Therefore, we propose that the strain YC6860^T might belong to a new genus and species, named Rugositalea oryzae. In addition, taxonomic analysis showed that YC6860^T is Gram-negative, aerobic, and rod-shaped with regular surface wrinkles under nutrient-limiting conditions, resembling a delicate twist of fusilli, with groove depths of 48.8 ± 3.7 nm and spacing of 122.5 ± 16.9 nm. This unique cell structure with regular rugosity could be the first finding that has not been reported in the existing bacterial morphology. Full article

Germplasm resources embody the genetic diversity of plants and form the foundation for breeding and the ongoing improvement of elite cultivars. The establishment of germplasm banks, along with their systematic evaluation, constitutes a critical step toward the conservation, sustainable use, and innovative utilization of these resources. Liriodendron, a rare and endangered tree genus with species distributed in both East Asia and North America, holds considerable ecological, ornamental, and economic significance. However, a standardized evaluation system for Liriodendron germplasm remains unavailable. In this study, 297 Liriodendron germplasm accessions were comprehensively evaluated using 34 phenotypic traits and whole-genome resequencing data. Substantial variation was observed in most phenotypic traits, with significant correlations identified among several characteristics. Cluster analysis based on phenotypic data grouped the accessions into three distinct clusters, each exhibiting unique distribution patterns. This classification was further supported by principal component analysis (PCA), which effectively captured the underlying variation among accessions. These phenotypic groupings demonstrated high consistency with subsequent population structure analysis based on SNP markers (K = 3). Notably, several key traits exhibited significant divergence (p < 0.05) among distinct genetic clusters, thereby validating the coordinated association between phenotypic variation and molecular markers. Genetic diversity and population structure were assessed using 4204 high-quality single-nucleotide polymorphism (SNP) markers obtained through stringent filtering. The results indicated that the Liriodendron sino-americanum displayed the highest genetic diversity, with an expected heterozygosity (He) of 0.18 and a polymorphic information content (PIC) of 0.14. In addition, both hierarchical clustering and PCA revealed clear population differentiation among the accessions. Association analysis between three phenotypic traits (DBH, annual height increment, and branch number) and SNPs identified 25 highly significant SNP loci (p < 0.01). Of particular interest, the branch number-associated locus SNP_17_69375264 (p = 1.03 × 10⁻⁵) demonstrated the strongest association, highlighting distinct genetic regulation patterns among different growth traits. A minimal set of 13 core SNP markers was subsequently used to construct unique DNA fingerprints for all 297 accessions. In conclusion, this study systematically characterized phenotypic traits in Liriodendron, identified high-quality and core SNPs, and established correlations between key phenotypic and molecular markers. These achievements enabled differential analysis and genetic diversity assessment of Liriodendron germplasm, along with the construction of DNA fingerprint profiles. The results provide crucial theoretical basis and technical support for germplasm conservation, accurate identification, and utilization of Liriodendron resources, while offering significant practical value for variety selection, reproduction and commercial applications of this species. Full article

Background: Multiple Myeloma (MM) is a malignant plasma cell dyscrasia that progresses through the consecutive asymptomatic, often undiagnosed, precancerous stages of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Asymptomatic Multiple Myeloma (SMM). MM is characterized by low survival rates, severe complications and drug resistance; therefore, understanding the molecular mechanisms of progression is crucial. This study aims to detect genetic mutations, both germline and somatic, that contribute to disease progression and drive tumorigenesis at the final stage of MM, using samples from patients presenting MGUS or SMM, and newly diagnosed MM patients. Methods: Mutations were identified through a fully computational pipeline, implemented in a Linux and RStudio environment, applied to each patient sequence, obtained through single-cell RNA-sequencing (scRNA-seq), separately. Structural and functional mutation types were identified by stage, along with the affected genes. The analysis included quality control, removal of the Unique Molecular Identifiers (UMIs), trimming, genome mapping and result visualization. Results: The findings revealed frequent germline and somatic mutations, with distinct structural and functional patterns across disease stages. Mutations in key genes were identified, pointing to molecules that may play a central role in carcinogenesis and disease progression. Notable examples include the HLA-A, HLA-B and HLA-C genes, as well as the KIF, EP400 and KDM gene families, with the first four already confirmed. Comparative analysis between the stages highlighted molecular transition events from one stage to another. Emphasis was given to novel genes discovered in newly diagnosed MM patients, that might contribute to the tumorigenesis that takes place. Conclusions: This study contributes to the understanding of the genetic basis of plasma cell dyscrasias and the transition events between the stages, offering insights that could aid in early detection and diagnosis, guide the development of personalized therapeutic strategies, and improve the understanding of mechanisms responsible for resistance to existing therapies. Full article