Search Results (3,904)

Background: Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous malignancy driven by structural variants (SVs) that impact diagnosis, prognosis, and treatment. Traditional methods such as karyotyping, FISH, and PCR often fail to detect cryptic or complex rearrangements, which are critical for accurate risk stratification. Methods: Optical Genome Mapping (OGM) is a technology that directly analyzes ultra-high-molecular-weight DNA, enabling the identification of balanced and unbalanced SVs, copy number variations (CNVs), and gene fusions with high resolution. This review compares the advantages and limitations of OGM versus standard techniques in ALL. Results: OGM improves ALL diagnosis by detecting clinically relevant alterations such as IKZF1 deletions, cryptic KMT2A rearrangements, and kinase fusions, especially in cases with normal or uninformative karyotypes. It reduces artifacts by eliminating cell culture and shortens reporting times. OGM resolves complex events like intrachromosomal amplifications and chromothripsis, enhancing classification and therapy decisions. Limitations include reduced sensitivity in repetitive regions, challenges in detecting Robertsonian translocations, difficulties with complex ploidies, and lower sensitivity for low-frequency subclones. Conclusions: Integrating OGM with next-generation sequencing (NGS) allows comprehensive genomic profiling, improving diagnosis, prognosis, and personalized treatment in ALL. Future advancements promise to further enhance the clinical utility of OGM. Full article

Background: The increasing attention on extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains isolated from poultry flocks stems from concerns about their virulence potential and zoonotic risk. Of particular significance is the identification of extraintestinal pathogenic E. coli (ExPEC) pathotypes in poultry, as these strains pose not only animal health concerns but also serious threats to food safety and public health. Mapping the genetic background of pathogenicity and antimicrobial resistance is essential for risk assessment and the development of effective control strategies. Methods: A total of 87 E. coli isolates were isolated from tracheal and cloacal swab samples collected from healthy chickens between 2022 and 2023. Whole-genome sequencing was performed using Illumina and MGI next-generation sequencing platforms. Bioinformatic analyses were conducted to identify virulence-associated genes and pathotype markers using multiple reference databases, including VirulenceFinder. The frequency of virulence genes was summarized both in tabular form and visualized through graphical representations. Results: A substantial proportion of the isolates harbored virulence genes linked to various ExPEC pathotypes, particularly uropathogenic E. coli (UPEC), avian pathogenic E. coli (APEC), and neonatal meningitis-causing E. coli (NMEC). The most frequently detected colonization factors included members of the fim, pap, ecp, and fae gene families. Among fitness-related genes, iron acquisition systems—ent, chu, iro, iuc, fep, and ybt—were especially prevalent. Classic UPEC-associated genes such as pap and fimH, along with the APEC-related iutA and vat, were found at high frequencies. Four isolates exhibited a virulence gene profile characteristic of the NMEC pathotype (ibeA, kpsD/M/T, fimH). In contrast, hallmark genes of enteric pathotypes were absent from all isolates. Conclusions: The predominance of extraintestinal virulence factors in the examined poultry-derived E. coli strains underscores their zoonotic potential. The complete absence of enteric pathotype markers indicates that the studied poultry populations primarily harbor ExPEC-like strains. These findings highlight the critical need for ongoing genomic surveillance and targeted preventive strategies within poultry production systems. Full article

MicroRNAs (miRNAs) are key regulators of gene expression with critical roles in oncogenic signaling. Endometrial cancer (EC) has been redefined with the identification of POLE-ultramutated tumors which, despite their hypermutated phenotype, show more favorable prognosis. We profiled miRNA expression in tumor tissues from forty (40) EC patients and twenty (20) healthy controls using qPCR panels. POLE exonuclease domain mutations (P286R, V411L) were genotyped, and subgroup analyses were conducted between POLE-mutated (n = 7) and POLE-wild-type (n = 33) tumors. Bioinformatic analyses included validated miRNA–mRNA interactions, target enrichment, and Gene Ontology (GO) pathway mapping. Comparison of EC versus healthy endometrium revealed 50 significantly dysregulated (∣log₂ (FoldReg)∣ > 1 and BH FDR < 0.05) miRNAs, including up-regulation of the oncogenic hsa-miR-181a-5p, hsa-miR-23a-3p, hsa-miR-200c-3p, and down-regulation of tumor-suppressive let-7 family members. Target enrichment implicated canonical oncogenic regulators such as MYC, TP53, and VEGFA. POLE-mutated tumor analysis demonstrated a miRNA signature, with 19 miRNAs significantly down-regulated, including let-7f-5p and hsa-miR-200b-3p. Findings for the EC versus healthy endometrium comparison were validated against TCGA-UCEC sequencing data which confirmed concordant dysregulation of key miRNAs across platforms. Our findings reveal that EC is characterized by widespread miRNA deregulation, with a unique global down-regulation signature in POLE-mutated tumors. These results highlight the potential of miRNAs as complementary biomarkers for classification and potential targets in EC. Full article

Milk protein content represents a key economic trait in dairy production, yet the genetic architecture underlying this trait remains unexplored in Romanian dual-purpose cattle breeds. This study conducted a genome-wide association analysis for milk protein content in 313 Romanian Simmental (n = 271) and Romanian Brown (n = 42) cows belonging to the Research and Development Station for Bovine Arad, Romania. Following quality control, 33,531 SNPs were tested for association with protein percentage adjusted for other effects (breed, days in milk, season, year, parity) using linear regression with the first five principal components as covariates to control population stratification. Although no SNP reached genome-wide significance (p < 5 × 10⁻⁸), one SNP achieved significance (p< 2.98 × 10⁻⁵) and seven additional SNPs exceeded the nominal threshold (p< 1 × 10⁻⁴) across six chromosomes. The strongest association (p = 9.56 × 10⁻⁶) mapped to chromosome 25 near C7orf61. Biologically relevant candidate genes included KLF6 on chromosome 13, previously associated with milk traits in Chinese Holstein, and AHCYL1 on chromosome 3, involved in calcium homeostasis. These findings provide initial insights into genomic regions influencing milk protein content in Romanian dual-purpose cattle, though validation in larger cohorts needs to be carried out. Full article

Despite the recognized social and economic importance of common beans (Phaseolus vulgaris L.), the average grain yield is far below the productive potential of cultivars. This situation is explained by several factors, such as the large number of diseases and pests that affect the crop, some of which cause significant damage. It is estimated that approximately 200 diseases can significantly affect common beans. These can be bacterial, viral, fungal, and nematode-induced. The main bean fungal diseases include anthracnose, angular leaf spot, powdery mildew, gray mold, Fusarium wilt, dry root rot, Pythium root rot, southern blight, white mold, charcoal rot and rust. This review provides a comprehensive overview of eleven major fungal diseases affecting common bean, describing their associated damage, characteristic symptomatology, and the epidemiological factors that favor disease development. It further synthesizes current knowledge on host resistance mechanisms that can be exploited to develop molecularly informed resistant genotypes. The compilation includes characterized resistance genes and mapped quantitative trait loci (QTLs), with details on their chromosomal locations, genetic effects, and potential for use in breeding. Moreover, the review highlights successful applications of molecular breeding approaches targeting fungal resistance. Finally, it discusses conclusions and future perspectives for integrating advanced genetic improvement strategies—such as marker-assisted selection, genomic selection, gene editing, and pyramiding—to enhance durable resistance to fungal pathogens in common bean. This work serves as both a reference for forthcoming resistance-mapping studies and a guide for the strategic selection of resistance loci in breeding programs aimed at developing cultivars with stable and long-lasting fungal resistance. Full article

Background/Objectives: The mTOR serine/threonine kinase coordinates protein translation, cell growth, and metabolism, and its dysregulation promotes tumorigenesis. We present a reproducible, pan-cancer, network-aware framework that integrates curated resources with genomics to move beyond pathway curation, yielding falsifiable hypotheses and prioritized candidates for mTOR axis biomarker validation. Materials and Methods: We assembled MTOR-related genes and interactions from GeneCards, KEGG, STRING, UniProt, and PathCards and harmonized identifiers. We formulated a concise working model linking genotype → pathway architecture (mTORC1/2) → expression-level rewiring → phenotype. Three analyses operationalized this model: (i) pan-cancer alteration mapping to separate widely shared drivers from tumor-specific nodes; (ii) expression-based activity scoring to quantify translational/nutrient-sensing modules; and (iii) topology-aware network propagation (personalized PageRank/Random Walk with Restart on a high-confidence STRING graph) to nominate functionally proximal neighbors. Reproducibility was supported by degree-normalized diffusion, predefined statistical thresholds, and sensitivity analyses. Results: Gene ontology analysis demonstrated significant enrichment for mTOR-related processes (TOR/TORC1 signaling and cellular responses to amino acids). Database synthesis corroborated disease associations involving MTOR and its partners (e.g., TSC2, RICTOR, RPTOR, MLST8, AKT1 across selected carcinomas). Across cohorts, our framework distinguishes broadly shared upstream drivers (PTEN, PIK3CA) from lineage-enriched nodes (e.g., RICTOR-linked components) and prioritizes non-mutated, network-proximal candidates that align with mTOR activity signatures. Conclusions: This study delivers a transparent, pan-cancer framework that unifies curated biology, genomics, and network topology to produce testable predictions about the mTOR axis. By distinguishing shared drivers from tumor-specific nodes and elevating non-mutated, topology-inferred candidates, the approach refines biomarker discovery and suggests architecture-aware therapeutic strategies. The analysis is reproducible and extensible, supporting prospective validation of prioritized candidates and the design of correlative studies that align pathway activity with clinical response. Full article

Cotton is a globally important crop, with fiber quality traits governed by complex quantitative trait loci (QTL). However, the utility of QTL data is often limited due to inconsistencies across studies. This study conducted a comprehensive Meta-QTL (MQTL) analysis by integrating 2864 QTLs from 50 independent studies published between 2000 and 2024. Of these, 2162 high-confidence QTLs were projected onto a consensus genetic map using BioMercator V4.2.3, resulting in the identification of 75 MQTLs across the cotton genome. These MQTLs exhibited significantly reduced confidence intervals and enhanced statistical support, with 14 MQTLs reported for the first time. Several MQTLs, including MQTLchr7-1, MQTLchr14-1, and MQTLchr24-1, were identified as stable clusters harboring key fiber quality and stress tolerance traits. Candidate gene analysis within select MQTL regions revealed 75 genes, 38 of which were annotated with significant gene ontology terms related to lignin catabolism, flavin binding, and stress responses. Notably, GhLAC-4, GhCTL2, and UDP-glycosyltransferase 92A1 were highlighted for their potential roles in fiber development and abiotic stress tolerance. These findings provide a refined genomic framework for cotton improvement and offer valuable resources for marker-assisted selection (MAS) and functional genomics aimed at enhancing fiber quality, yield, and stress resilience in cotton breeding programs. Full article

Magnesium (Mg) release (MGR) proteins play a crucial role in maintaining Mg²⁺ homeostasis in plant cells. However, MGR family genes have not yet been explored in crops. This study identified the wheat MGR (TaMGR) family members via BlastP alignment. A total of 15 MGR genes were mapped to 12 chromosomes. Cis-element prediction in the promoter region revealed that the ABA-responsive element (ABRE) was 100% conserved among all family members. Collinearity analysis indicates that MGR genes in monocot plants may have higher conservation compared to dicot plants. Expression profiling analyses uncovered the expression patterns of TaMGR genes across diverse tissues and under various stresses. Our results demonstrated that TaMGR5D and TaMGR5A.2 were significantly induced by both powdery mildew and stripe rust pathogen infections, whereas TaMGR4A transcript levels were upregulated in response to drought, heat and their combined stress. These findings indicate that TaMGRs may contribute coordinately to the regulation of wheat growth and development as well as adaptive responses to adverse conditions through member-specific expression patterns. This study systematically identified and analyzed the evolution and expression regulation characteristics of TaMGRs, providing a theoretical basis for in-depth research on the functional mechanisms of the TaMGRs and for improving the Mg use efficiency and stress adaptability of wheat via molecular approaches. Full article

Obesity is a highly complex, multifactorial disease influenced by dynamic interactions among genetic, epigenetic, environmental, and behavioral determinants that explicitly position genetics as the core. While advances in multi-omic integration have revolutionized our understanding of adiposity pathways, translation into personalized clinical nutrition remains a critical challenge. This review systematically consolidates emerging insights into the molecular and nutrigenomic architecture of obesity by integrating data from large-scale GWAS, functional epigenomics, nutrigenetic interactions, and microbiome-mediated metabolic programming. The primary aim is to systematically organize and synthesize recent genetic and genomic findings in obesity, while also highlighting how these discoveries can be contextualized within precision nutrition frameworks. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science up to July 2024 using MeSH terms, nutrigenomic-specific queries, and multi-omics filters. Eligible studies were classified into five domains: monogenic obesity, polygenic GWAS findings, epigenomic regulation, nutrigenomic signatures, and gut microbiome contributions. Over 127 candidate genes and 253 QTLs have been implicated in obesity susceptibility. Monogenic variants (e.g., LEP, LEPR, MC4R, POMC, PCSK1) explain rare, early-onset phenotypes, while FTO (polygenic) and MC4R (monogenic mutations as well as common polygenic variants) represent major loci across populations. Epigenetic mechanisms, dietary composition, physical activity, and microbial diversity significantly recalibrate obesity trajectories. Integration of genomics, functional epigenomics, precision nutrigenomics, and microbiome science presents transformative opportunities for personalized obesity interventions. However, translation into evidence-based clinical nutrition remains limited, emphasizing the need for functional validation, cross-ancestry mapping, and AI-driven precision frameworks. Specifically, this review systematically identifies and integrates evidence from genomics, epigenomics, nutrigenomics, and microbiome studies published between 2000 and 2024, applying structured inclusion/exclusion criteria and narrative synthesis to highlight translational pathways for precision nutrition. Full article

Cisplatin is a widely used antineoplastic agent whose therapeutic efficacy is often limited by its adverse effects on the central nervous system. In this exploratory study, we characterized the transcriptomic impact of a cumulative cisplatin regimen on the male Wistar rat brain using microarray technology. Differentially expressed genes were identified, and their functional roles were investigated through enrichment analyses (KEGG) and Gene Ontology (GO), and the construction of protein–protein interaction (PPI) networks. Our results revealed significant alterations in pathways related to synaptic signaling, neuroplasticity, and cellular metabolism. To generate translational hypotheses, these findings were subsequently correlated in silico with public human lower-grade glioma (LGG) datasets, which suggested a potential association between key cisplatin-regulated genes and clinical prognosis and immune cell infiltration patterns. This manuscript does not include RT-qPCR (or Western blot) validation; results should be interpreted as hypothesis-generating and require orthogonal confirmation. These findings provide a comprehensive transcriptomic map of cisplatin-induced neurotoxicity, offering novel insights into its underlying molecular mechanisms and identifying a rich set of candidate targets for future neuroprotective strategies. Full article

The ciliary marginal zone (CMZ) is a region in the peripheral-most retina that displays ongoing retinogenesis during growth and expansion of the eye in adulthood. While there is evidence that this capacity also exists in birds and mammals, it is far more robust in fish and amphibians. The process of CMZ retinogenesis is essentially equivalent to that seen early in the central retina; however, its regulation is not fully understood. In a previous study, we attempted to uncover novel regulatory genes by using a forward genetics screen in zebrafish, looking for recessive CMZ mutants. One of the mutants found was called no marginal zone (nmz). The nmz mutant showed relatively normal central retina development, but a lack of cells in the CMZ by 5 days post fertilization (dpf). Mapping, genomic sequencing, and complementation analysis using a second mutant line (m863) isolated in another laboratory showed that a mutation in damage-specific DNA binding protein-1 (ddb-1) gene underlies the phenotype seen in nmz. BrdU labeling suggested that later expansion and differentiation of CMZ retinal progenitors is more affected by ddb-1 loss than the earlier process of stem cell asymmetric division. As was seen for the m863 mutant and in other studies with mice, one profound effect of ddb-1 loss in nmz was the upregulation in expression of tp53 and several of its downstream effectors. Several important genes important in CMZ retinogenesis are also downregulated in the nmz mutant. The change in gene expression would suggest that ddb-1 loss leads to increased cell cycle disruption and apoptosis at the expense of CMZ retinogenesis. While homozygosity is lethal, heterozygous fish appear to be completely normal in morphology, visual function, and behavior. Full article

Sporothrix schenckii is a pathogenic fungus with both clinical and environmental origins that was traditionally described as a single species but is increasingly recognized as being genetically diverse. In this study, we analyzed multiple isolates recovered from human sporotrichosis cases and environmental sources across Latin America (Mexico, Guatemala, Colombia). We conducted a polyphasic analysis of 16 isolates, integrating morphological data with multilocus sequence analysis (MLSA) targeting the internal transcribed spacer (ITS), calmodulin (CAL), β-tubulin (BT2), and translation elongation factor 1-α (TEF) gene regions. Phylogenetic relationships were resolved via maximum likelihood, and genetic structure was corroborated via four independent clustering methods: minimum spanning tree, principal component analysis, multidimensional scaling, and self-organizing maps. MLSA reidentified six isolates as S. globosa and confirmed the absence of S. brasiliensis in the cohort. The remaining S. schenckii s. str. isolates were resolved into three clades (A, B, and C). Notably, clade B (EH748, EH194, and EH257) formed a genetically divergent cluster with the highest nucleotide diversity (π = 0.03556) and was consistently segregated by all clustering algorithms. Clinical and environmental isolates were phylogenetically intermingled, supporting an active environmental reservoir for human infections. Phenotypic data, including colony size and conidial and yeast dimensions, varied but did not clearly distinguish between clinical and environmental origins. Our study provides compelling molecular evidence for a previously unrecognized, highly divergent clade within S. schenckii s. str., indicative of ongoing cryptic speciation. These findings refine the taxonomy of medically important Sporothrix species and reveal a distinct epidemiological profile for sporotrichosis in the studied regions, separate from the S. brasiliensis-driven epizootic. This highlights the critical role of molecular surveillance for accurate diagnosis, treatment, and public health strategies. Full article

Chloroplast codon usage bias (CUB) records both maternal phylogeny and selection intensity. Characterizing CUB in the synthetic cereal × Triticosecale and its Triticum and Secale parents is therefore a prerequisite for plastid-based engineering and for tracing the evolutionary consequences of recent allopolyploidy. Complete plastome sequences of five taxa—Triticum monococcum, T. turgidum, T. aestivum, Secale cereale and × Triticosecale sp.—were downloaded. Protein-coding genes were extracted to calculate overall GC, GC1–GC3, SCUO, RSCU, ENC-GC3s, neutrality, and PR2 plots. Optimal codons were defined as RSCU ≥ 1 and △RSCU ≥ 0.8. The results showed that the chloroplast genomes of these five species are low in GC content for the third base of codons, suggesting an end preference for A or U bases. The SCUO values ranged from 0.22 to 0.23, suggesting no significant codon usage bias. GC content was relatively low (38.78–39.16%), with the order GC1 > GC2 > GC3. RSCU analysis indicated that codons ending with A/T are more commonly used. Neutral mapping, ENC-GC3s, and the PR2 plot all showed that the preference of codon usage for the majority of functional genes was influenced by a combination of mutation and natural selection pressure, and the influence of natural selection was predominant. RSCU clustering recovers the expected maternal tree (Triticum clade + triticale). All optimal codons terminate with A or U, yielding identical plastid translation tables for the five species. Despite its recent hybrid origin, triticale plastid CUB is indistinguishable from its wheat maternal ancestor and is governed mainly by selection. The compiled optimal codon set provides an immediate reference for chloroplast transformation and for dissecting selection relaxation in newly synthesized triticale combinations. Full article

This study aims to evaluate the restoration effect of artificially mixed-sown grasslands by investigating the characteristics of plant communities and soil fungal communities in long-term (22-year-established) artificial grasslands under six Poaceae mixture combinations. The experiment took mixed-sown grasslands of grass species established in 2002 on the Qinghai–Tibet Plateau as the research object. It employed ITS gene high-throughput sequencing technology to construct a fungal community distribution map and combined it with FUNGuild (Functional Guilds of Fungi) functional predictions to analyze fungal species abundance, structural diversity, molecular co-occurrence networks, and functional characteristics. By integrating Mantel test and RDA (redundancy analysis), we identified key environmental factors driving soil microbial community structure in mixed-sown grasslands and revealed the plant–soil–microbe interaction mechanisms in a Poaceae mixture grassland. The results showed that the HC treatment (a mixture of three grass species) significantly enhanced plant biomass and soil nutrient accumulation. In 2023 and 2024, its aboveground biomass increased by 66.14% and 60.91%, respectively, compared to the HA treatment (monoculture). Soil organic matter increased by 52.32% and 48.35%, while electrical conductivity decreased by 48.99% and 51.72%, respectively. The fungal community structure improved under the HD treatment (a mixture of four grass species), with an increased abundance of the dominant phylum Ascomycota and a 14.44% rise in the Shannon index compared to the HA treatment. The network complexity under the HF treatment (a mixture of six grass species) increased (with edge numbers reaching 494), while the functional abundance of plant pathogen was significantly lower than that under the HA treatment. Mantel test and RDA revealed that SEC (soil electrical conductivity) was significantly positively correlated with pH, while both exhibited negative correlations with other plant and soil physicochemical indicators. Moreover, SEC emerged as the core factor driving fungal community assembly. Mixed sowing of three to four grass species effectively regulated soil electrical conductivity, simultaneously enhancing plant biomass, soil nutrients, and fungal community diversity, representing an optimal strategy for artificial restoration of degraded grasslands. Full article

Preventive immunology is emerging as a cornerstone of animal infectious disease control within One Health, shifting emphasis from treatment to prevention. This review integrates mechanistic insights in host immunity with a comparative evaluation of next-generation interventions—mRNA/DNA and viral-vector vaccines, nanovaccines, monoclonal antibodies, cytokine modulators, probiotics/postbiotics, bacteriophages, and CRISPR-based approaches—highlighting their immunogenicity, thermostability, delivery, and field readiness. Distinct from prior reviews, we appraise diagnostics as preventive tools (point-of-care assays, biosensors, MALDI-TOF MS, AI-enabled analytics) that enable early detection, risk prediction, and targeted interventions, and we map quantifiable links between successful prevention and reduced antimicrobial use. We embed translation factors—regulatory alignment, scalable manufacturing, workforce capacity, equitable access in LMICs, and public trust—alongside environmental and zoonotic interfaces that shape antimicrobial resistance dynamics. We also provide a critical analysis of limitations and failure cases: gene editing may require stacked edits and concurrent vaccination; phage programs must manage host range, resistance, stability, and regulation; and probiotic benefits remain context-specific. Finally, we present a risk–benefit–readiness framework and a time-bound research agenda to guide deployment and evaluation across animal–human–environmental systems. Coordinating scientific innovation with governance and ethics can measurably reduce disease burden, curb antimicrobial consumption, and improve health outcomes across species. Full article