Search Results (787)

Dermatophytes are keratinophilic fungi that cause a wide range of superficial infections in humans and animals. The Trichophyton mentagrophytes species complex is one of the most clinically important groups due to its broad host range, widespread distribution, and increasing involvement in antifungal-resistant infections. Here, we described the epidemiology of T. mentagrophytes over a period of 4 years detected in the northeastern part of Italy and provided the genomic characterization of clinical isolates. ITS sequence analysis revealed that among the 13 strains studied, 11 belonged to the T. mentagrophytes complex. In detail, nine were classified as genotype I/II and two as genotype VII. Analysis of the SQLE gene revealed that nine strains harbored a wild-type gene, while two carried a Lys276Asn mutation. Genomic analysis was performed on three clinical T. mentagrophytes strains that belonged to genotype I/II, revealing the presence of different virulence factors including MEP-1, MEP-2, MEP-3, and MEP-5. Phylogenetic analysis based on core-genome SNPs demonstrated that the two genomes included in this study were clonally related to a T. mentagrophytes strain isolated in China in 2024. In conclusion, our study highlights the importance of genomic characterization in order to trace the epidemiology of dermatophytes worldwide and to characterize emerging strains. Full article

Background/Objectives: The gene pool of the Apennine wolf is affected by admixture with domestic variants due to anthropogenic hybridisation with dogs. Genetic monitoring at the population level involves assessing the extent of admixture in single individuals, ranging from pure wolves to recent hybrids or wolf backcrosses, through the analysis of nuclear and mitochondrial DNA (mtDNA) markers. Although individually non-diagnostic, mtDNA is nevertheless essential for completing the final diagnosis of genetic admixture. Typically, the identification of wolf mtDNA haplotypes is carried out via sequencing of coding genes and non-coding DNA stretches. Our objective was to develop a fast real-time PCR assay to detect the mtDNA haplotypes that occur exclusively in the Apennine wolf population, as a valuable alternative to the demanding sequence-based typing. Methods: We validated a qualitative duplex real-time PCR that exploits the combined presence of diagnostic point mutations in two mtDNA segments, the NDH-4 gene and the control region, and is performed in a single-tube step through TaqMan-MGB chemistry. The aim was to detect mtDNA multi-fragment haplotypes that are exclusive to the Apennine wolf, bypassing sequencing. Results: Basic validation of 149 field samples, consisting of pure Apennine wolves, dogs, wolf × dog hybrids, and Dinaric wolves, showed that the assay is highly specific and sensitive, with genomic DNA amounts as low as 10⁻⁵ ng still producing positive results. It also proved high repeatability and reproducibility, thereby enabling reliable high-throughput testing. Conclusions: The results indicate that the assay presented here provides a valuable alternative method to the time- and cost-consuming sequencing procedure to reliably diagnose the maternal lineage of the still-threatened Apennine wolf, and it covers a wide range of applications, from scientific research to conservation, diagnostics, and forensics. Full article

The Millard’s rat (Dacnomys millardi), a threatened murid endemic to Southeast Asian montane rainforests and the sole member of its monotypic genus, faces escalating endangered risks as a Near Threatened species in China’s Biodiversity Red List. This ecologically specialized rodent exhibits diagnostic morphological adaptations—hypertrophied upper molars and cryptic pelage—that underpin niche differentiation in undisturbed tropical/subtropical forests. Despite its evolutionary distinctiveness, the conservation prioritization given to Dacnomys is hindered due to a deficiency of data and unresolved phylogenetic relationships. Here, we integrated morphological analyses with the first complete mitogenome (16,289 bp in size; no structural rearrangements) of D. millardi to validate its phylogenetic placement within the subfamily Murinae and provide novel insights into genetic diversity erosion. Bayesian and maximum likelihood phylogenies robustly supported Dacnomys as sister to Leopoldamys (PP = 1.0; BS = 100%), with an early Pliocene divergence (~4.8 Mya, 95% HPD: 3.65–5.47 Mya). Additionally, based on its basal phylogenetic position within Murinae, we propose reclassifying Micromys from Rattini to the tribe Micromyini. Codon usage bias analyses revealed pervasive purifying selection (Ka/Ks < 1), constraining mitogenome evolution. Genetic diversity analyses showed low genetic variation (CYTB: π = 0.0135 ± 0.0023; COX1: π = 0.0101 ± 0.0025) in fragmented populations. We propose three new insights into this genetic diversity erosion. (1) Evolutionary constraints: genome-wide evolutionary conservation and shallow evolutionary history (~4.8 Mya) limited mutation accumulation. (2) Anthropogenic pressures: deforestation-driven fragmentation of habitats (>20,000 km²/year loss since 2000) has reduced effective population size, exacerbating genetic drift. (3) Ecological specialization: long-term adaptation to stable niches favored genomic optimization over adaptive flexibility. These findings necessitate suitable conservation action by enforcing protection of core habitats to prevent deforestation-driven population collapses and advocating IUCN reclassification of D. millardi from Data Deficient to Near Threatened. Full article

Fusarium root rot, caused by Fusarium equiseti, poses a significant threat to soybean production. This study aimed to explore the genetic basis of resistance to Fusarium equiseti root rot (FERR) by evaluating the resistance phenotype of 346 soybean germplasms and conducting a genome-wide association study (GWAS) using 698,949 SNP markers obtained from soybean germplasm resequencing data. GWAS analysis identified 101 SNPs significantly associated with FERR resistance, distributed across nine chromosomes, with the highest number of SNPs on chromosomes 13 and 20. Further gene-based association and allele variation analyses identified candidate genes whose mutations are closely related to FERR resistance. To accelerate soybean FERR resistance breeding screening, we developed CAPS markers S13_14464319-CAPS1 and S15_9215524-CAPS2, targeting these SNP sites, and KASP markers based on the S15_9205620-G/A, providing an effective tool for marker-assisted selection (MAS). This study offers a valuable theoretical foundation and molecular marker resources for the functional validation of FERR resistance genes and soybean disease resistance breeding. Full article

Background/Objectives: Senior-Loken syndrome (SLS) is a rare autosomal recessive renal–retinal disease caused by mutations in 10 genes. This study aimed to review the ophthalmic findings, renal function, and genotypes of Korean SLS cases. Methods: We retrospectively reviewed 17 genetically confirmed SLS patients in Korea, including 9 newly identified cases and 8 previously reported. Comprehensive ophthalmologic evaluations and renal assessments were conducted. Genetic testing was performed using whole-genome sequencing (WGS), whole-exome sequencing (WES), or Sanger sequencing. Results: Among the 17 patients, patients with NPHP1 mutations were most common (35.3%), followed by those with NPHP4 (29.4%), IQCB1 (NPHP5, 29.4%), and SDCCAG8 (NPHP10, 5.9%) mutations. Patients with NPHP1 mutations showed retinitis pigmentosa (RP) sine pigmento and preserved central vision independent of renal deterioration. Patients with NPHP4 mutations showed early renal dysfunction. Two patients aged under 20 maintained relatively good visual function, but older individuals progressed to severe retinopathy. Patients with IQCB1 mutations were generally prone to early and severe retinal degeneration, typically manifesting as Leber congenital amaurosis (LCA) (three patients), while two patients exhibited milder RP sine pigmento with preserved central vision. Notably, two out of five (40.0%) maintained normal renal function at the time of diagnosis, and both had large deletions in IQCB1. The patient with SDCCAG8 mutation exhibited both end-stage renal disease and congenital blindness due to LCA. Wide-field fundus autofluorescence (AF) revealed perifoveal and peripapillary hypoAF with a perifoveal hyperAF in younger patients across genotypes. Patients under 20 years old showed relatively preserved central vision, regardless of the underlying genetic mutation. Conclusions: The clinical manifestation of renal and ocular impairment demonstrated heterogeneity among Korean SLS patients according to causative genes, and the severity of renal dysfunction and visual decline was not correlated. Therefore, simultaneous comprehensive evaluations of both renal and ocular function should be performed at the initial diagnosis to guide timely intervention and optimize long-term outcomes. Full article

Meiotic recombination is a key evolutionary process that generates novel allele combinations during prophase I of meiosis, promoting genetic diversity and enabling the selection of desirable traits in livestock breeding. Although its molecular mechanisms are well-characterised in model organisms such as humans and mice, studies in African indigenous cattle, particularly South African breeds, remain scarce. Key regulators of recombination, including PRDM9, SPO11, and DMC1, play essential roles in crossover formation and genome stability, with mutations in these genes often linked to fertility defects. Despite the Bonsmara and Nguni breeds’ exceptional adaptability to arid and resource-limited environments, little is known about how recombination contributes to their unique genetic architecture and adaptive traits. This review synthesises the current knowledge on the molecular basis of meiotic recombination, with a focus on prophase I events and associated structural proteins and enzymes. It also highlights the utility of genome-wide tools, particularly high-density single nucleotide polymorphism (SNP) markers for recombination mapping. By focusing on the underexplored recombination landscape in South African beef cattle, this review identifies key knowledge gaps. It outlines how recombination studies can inform breeding strategies aimed at enhancing genetic improvement, conservation, and the long-term sustainability of local beef production systems. Full article

Background: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an escalating global health challenge, affecting over 82 million individuals each year. The increasing resistance to commonly used antibiotics such as azithromycin, ciprofloxacin, and cefixime hinders timely and effective treatment, primarily due to the delayed detection of resistant strains. Methods: To overcome these limitations, a hybrid machine learning (ML) and deep learning (DL) framework was developed using a dataset comprising 3786 N. gonorrhoeae isolates. The dataset included clinical metadata and phenotypic resistance profiles. The preprocessing steps involved handling 23% data sparsity, imputing 31 skewed columns, and applying resampling and harmonisation techniques sensitive to data skewness. A predictive pipeline was constructed using both clinical variables and genomic unitigs, and a suite of 33 classifiers was evaluated. Results: The CatBoost model emerged as the top-performing ML algorithm, particularly due to its proficiency in handling categorical data, while a three-layered neural network served as the DL baseline. The ML models outperformed genome-wide association study (GWAS) benchmarks, achieving AUC scores of 0.97 (ciprofloxacin), 0.95 (cefixime), and 0.94 (azithromycin), representing a 4–7% improvement. SHAP analysis identified biologically relevant resistance markers, such as penA mosaic alleles and mtrR promoter mutations, validating the interpretability of the model. Conclusions: The study highlights the potential of ML-driven approaches to enhance the real-time prediction of antimicrobial resistance in N. gonorrhoeae. These methods can significantly contribute to antibiotic stewardship programs, although further validation is required in low-resource settings to confirm their generalisability and robustness across diverse populations. Full article

Brassica napus is one of the most important oil crops. Rapid breeding of excellent genotypes is an important aspect of breeding. As a cutting-edge and reliable technique, genome-wide selection (GS) has been widely used and is influenced by many factors. In this study, ten phenotypic traits of two populations were studied, including oleic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3), glucosinolate (GSL), seed oil content (SOC), and seed protein content (SPC), silique length (SL), days to initial flowering (DIF), days to final flowering (DFF), and the flowering period (FP). The effects of different GS models, marker densities, population designs, and the inclusion of nonadditive effects, trait-specific SNPs, and deleterious mutations on GS were evaluated. The results highlight the superior prediction accuracy (PA) under the RF model. Among the ten traits, the PA of glucosinolate was the highest, and that of linolenic acid was the lowest. At the same time, 5000 markers and a population of 400 samples, or a training population three times the size of an applied breeding population, can achieve optimal performance for most traits. The application of nonadditive effects and deleterious mutations had a weak effect on the improvement of traits with high PA but was effective for traits with low PA. The use of trait-specific SNPs can effectively improve the PA, especially when using markers with p-values less than 0.1. In addition, we found that the PA of traits was significantly and positively correlated with the number of markers, according to p-values less than 0.01. In general, based on the associated population, a GS system suitable for B. napus was established in this study, which can provide a reference for the improvement of GS and is conducive to the subsequent application of GS in B. napus, especially in the aspects of model selection of GS, the application of markers, and the setting of population sizes. Full article

Aeromonas salmonicida is an age-old fish pathogen widely distributed in seawater and freshwater environments that causes significant economic losses to the global aquaculture industry. Genetic mutations and the emergence of thermophilic strains are factors in the continuous expansion of A. salmonicida’s host range. Beyond infecting fish, A. salmonicida poses a potential threat to mammalian and human health. This review synthesizes recent global research advances concerning A. salmonicida, encompassing strain characteristics, genomic features, virulence factors, and pathogenic mechanisms, as well as the clinical manifestations in infected fish and mammals, and discusses prevention and treatment methods. Particular emphasis is placed on evaluating the potential prophylactic roles of Chinese herbs and bacteriophages against A. salmonicida infection. Furthermore, the review provides perspectives on future research directions, diagnostics, and disease management, informed by contemporary domestic and international studies on this pathogen. Full article

Background/Objectives: Ceftiofur hydrochloride (CEF) is a third-generation cephalosporin widely used in cattle to treat various disease. The recommended dosage was 1.1 to 2.2 mg/kg BW for 3 to 5 consecutive days by intramuscular or subcutaneous injection. Incomplete treatment, overuse, or misuse, often observed in clinical practice, are major contributors to resistance development. This study aims to explore how different concentrations, durations, and dosing frequencies affect susceptibility and bactericidal efficacy of Staphylococcus aureus to optimize CEF dosage regimens. Methods: First, CEF was intermittently administered at 1/2 × minimum inhibitory concentration (MIC), 2 × MIC, 6 × MIC, and 100 × MIC for 30 cycles. Second, CEF was continuously administered for 48, 72, 96, 120, 144, and 168 h. Bacterial susceptibility, regrowth, survival rate, and the emergence of persisters or tolerant phenotypes were assessed. Genetic mutations were identified by whole-genome resequencing. Membrane permeability, integrity, and efflux pump activity were analyzed to elucidate the mechanism of CEF. Results: After 30 cycles, the MIC increased eight-fold in the 2 × MIC group. No significant MIC increase was found in other groups, but a progression from susceptibility to persistence and then to tolerance was observed in the 100 × MIC intermittent group. The survival rate increased both in the 2 × MIC and 100 × MIC groups. With continuous exposure to ≥6 × MIC over 120 h, strains were completely eradicated without MIC increase. Resistance-associated single-nucleotide polymorphism (SNP) mutations were detected only in strains of the 2 × MIC and 100 × MIC intermittent groups. CEF altered the membrane hydrophobicity, damaging membrane integrity after 30 cycles. Conclusions: These findings suggest that high-dose, prolonged exposure is more effective for eliminating Staphylococcus aureus and avoiding resistance, whereas intermittent dosing may promote persistence, tolerance, and resistance evolution. Full article

Fucosylation plays a fundamental role in maintaining cellular functions and biological processes across all animals. As a form of glycosylation, it involves the biochemical addition of fucose, a six-carbon monosaccharide, to biological molecules like lipids, proteins, and glycan chains. This modification is essential for optimizing cellular interactions required for receptor-ligand binding, cell adhesion, immune responses, and development. Disruptions in cellular fucose synthesis or in the mechanisms enabling its transfer to other molecules have been linked to human disease. Inherited defects in the fucosylation pathway are rare, with about thirty patients described. Through genome-wide association studies (GWAS), variants in fucosylation pathway genes have been associated with complex diseases such as glaucoma and stroke, and somatic mutations are often found in cancers. Recent studies have applied targeted genetic animal models to elucidate the mechanisms through which disruptions in fucosylation contribute to disease pathogenesis and progression. Key focus areas include GDP-fucose synthesis through de novo or salvage pathways, GDP-fucose transport into the Golgi and endoplasmic reticulum (ER), and its transfer by fucosyltransferases (FUTs) or protein O-fucosyltransferases (POFUTs) onto acceptor molecules. Loss or gain of function fucosylation gene mutations in animal models such as mice, zebrafish, and invertebrates have provided insights into some fucosylation disease pathogenesis. This review aims to bring together these findings, summarizing key insights from existing animal studies to possibly infer fucosylation disease mechanisms in humans. Full article

Transmembrane channel-like (TMC) proteins are essential for hearing and balance; however, the molecular mechanisms that regulate their proper folding and membrane targeting remain poorly understood. Here, we establish Caenorhabditis elegans as a genetically tractable model to dissect TMC-1 trafficking by combining CRISPR knock-in strains, super-resolution microscopy, and genome-wide forward genetic screening. We show that TMC-1 robustly localizes to the plasma membrane in both neurons and muscle cells and identify a conserved valine (V803) in transmembrane domain 9 (TM9) as critical for its biogenesis and trafficking. Structural analyses guided by AlphaMissense and AlphaFold uncover two evolutionarily conserved functional hotspots, one in the extracellular loop adjacent to TM9 and the other in the TMC signature motif, which are interconnected by an evolutionarily conserved disulfide bond. Disrupting this bond in worm TMC-1 abolishes its cell-surface localization and destabilizes the mechanotransduction channel complex. Together, these findings provide a structural framework for interpreting deafness-causing mutations in human TMC1 and highlight disulfide-bond-linked hotspots as key molecular determinants of TMC protein biogenesis and trafficking. Full article

Erythropoiesis, the process driving the differentiation of hematopoietic stem and progenitor cells to mature erythrocytes, unfolds through tightly orchestrated developmental stages, each defined by profound epigenetic remodeling. From the initial commitment of hematopoietic progenitors to the terminal enucleation of erythrocytes, dynamic changes in chromatin accessibility, transcription factor occupancy, and three-dimensional genome architecture govern lineage specification and stage-specific gene expression. Advances in our understanding of the regulatory genome have uncovered how non-coding elements, including enhancers, silencers, and insulators, shape the transcriptional landscape of erythroid cells. These elements work in concert with lineage-determining transcription factors to establish and maintain erythroid identity. Disruption of these epigenetic programs—whether by inherited mutations, somatic alterations, or environmental stress—can lead to a wide range of hematologic disorders. Importantly, this growing knowledge base has opened new therapeutic avenues, enabling the development of precision tools that target regulatory circuits to correct gene expression. These include epigenetic drugs, enhancer-targeted genome editing, and lineage-restricted gene therapies that leverage endogenous regulatory logic. As our understanding of erythroid epigenomics deepens, so too does our ability to design rational, cell-type-specific interventions for red blood cell disorders. Full article

Lung adenocarcinoma (LUAD) is characterized by substantial genetic heterogeneity, making it challenging to identify reliable biomarkers for diagnosis and treatment. Tumor mutational burden (TMB) is widely recognized as a predictive biomarker due to its association with immune response and treatment efficacy. In this study, we take a different approach by treating TMB as a response variable to uncover its genetic drivers using multiomics data. We conducted a thorough evaluation of recent feature selection methods through extensive simulations and identified three top-performing approaches: projection correlation screening (PC-Screen), distance correlation sure independence screening (DC-SIS), and Wasserstein distance-based screening (WD-Screen). Unlike traditional approaches that rely on simple statistical tests or dataset splitting for validation, we adopt a method-based validation strategy, selecting top-ranked features from each method and identifying consistently selected genes across all three. Using The Cancer Genome Atlas (TCGA) dataset, we integrated copy number alteration (CNA), mRNA expression, and DNA methylation data as predictors and applied our selected methods. In the two-platform analysis (mRNA + CNA), we identified 13 key genes, including both previously reported LUAD-associated genes (CCNG1, CKAP2L, HSD17B4, SHROOM1, TIGD6, and TMEM173) and novel candidates (DTWD2, FLJ33630, NME5, NUDT12, PCBD2, REEP5, and SLC22A5). Expanding to a three-platform analysis (mRNA + CNA + methylation) further refined our findings, with PCBD2 and TMEM173 emerging as the robust candidates. These results highlight the complexity of multiomics integration and the need for advanced feature selection techniques to uncover biologically meaningful patterns. Our multiomics strategy and robust selection approach provide insights into the genetic determinants of TMB, offering potential biomarkers for targeted LUAD therapies and demonstrating the power of Wasserstein distance-based feature selection in complex genomic analysis. Full article

Genetic dystonias are a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions that cause repetitive movements and abnormal postures. Often beginning in childhood, they can significantly affect quality of life. Although individually rare, genetic causes are collectively relevant in pediatric dystonias, with over 250 associated genes. Among these, TOR1A, SGCE, and KMT2B are the most frequently reported in pediatric forms. Diagnosis is challenging due to the wide clinical and genetic variability. Recent advances in genetic testing, including whole-exome and whole-genome sequencing, have improved the early identification of causative variants. Functional data on selected mutations are helping to refine genotype–phenotype correlations. Management typically requires a multidisciplinary approach. Symptomatic treatments include anticholinergics, benzodiazepines, and botulinum toxin, while deep brain stimulation can be effective in refractory cases, especially in patients with TOR1A variants. Disease-modifying therapies are also emerging, such as gene therapy for AADC deficiency, highlighting the potential of precision medicine. This review provides an updated overview of pediatric genetic dystonias, with a focus on differential diagnosis and treatment strategies. Early and accurate diagnosis, together with personalized care, is key to improving outcomes in affected children. Full article