Search Results (1,424)

Background: Seed shattering enhances ecological adaptation in perennial grasses but severely limits harvestable seed yield in forage crops. Psathyrostachys juncea is an important perennial forage species in arid and cold regions, yet the genetic basis of its seed shattering remains largely unknown. Here we asked which genomic regions and biological pathways underlie natural variation in seed shattering in P. juncea, and whether cellulose synthase (CESA)-mediated cell-wall formation contributes to abscission-zone strength. Results: We evaluated seed shattering in a diverse association panel of P. juncea across four environment–-year combinations and performed a genome-wide association study (GWAS) using genotyping-by-sequencing single-nucleotide polymorphism (SNP) markers. The analysis identified 36 significant SNP loci distributed on multiple chromosomes, consistent with a highly polygenic and environment-responsive architecture. Candidate-gene annotation highlighted pathways related to cell-wall biosynthesis, hormone signaling and sugar transport. Notably, in the BT23SHT environment a cluster of association signals on chromosome 3D co-localized with several genes annotated as cellulose synthase (CESA). Abscission-zone transcriptome profiling and qRT-PCR at 7, 14, 21 and 28 days after heading revealed that CESA genes, including TraesCS3D02G010100.1 located near the lead SNP Chr3D_3539055, showed higher early expression in low-shattering lines and a decline toward baseline in high-shattering lines. Comparative analyses placed P. juncea CESA proteins within a broadly conserved but lineage-divergent framework among grasses. Conclusion: Together, these results define the genetic landscape of seed shattering in P. juncea and nominate cellulose-biosynthetic genes on chromosome 3D as promising targets for marker-assisted selection of low-shattering, high-seed-yield forage cultivars. Full article

Viral zoonoses represent a critical intersection of global health, ecology, and ethical issues. Pathogens that pass from animals to humans. This review examines the complex landscape of viral zoonoses, including their mechanisms, impact, and mitigation strategies. We begin with insights into the historical context and significance of these diseases and then explore spillover mechanisms influenced by genetic, ecological, and anthropogenic factors. This review covers the host range, transmission dynamics, and immunological barriers, including viral detection, adaptation, and immune evasion. Genomic insights have revealed the genetic determinants of host switching and adaptation, illuminating the dynamics of viral spillover events. We emphasize the anticipation and prevention of zoonotic events, highlighting surveillance, early warning systems, and the “One Health” approach. Using case studies of outbreaks such as Ebola, avian influenza, and COVID-19, this review examines the real-world consequences of zoonotic diseases. We then discuss interventions, including mitigation strategies and vaccination, and their ethical and social implications. Drawing on past outbreaks, we provide recommendations for the future, aiming to balance human health, conservation, and animal welfare. This review aims to inform professionals, academics, and policymakers by offering a multidisciplinary perspective on the complex world of viral zoonoses and strategies to protect global health. Full article

Methamphetamine is a highly addictive stimulant with severe health and psychosocial consequences. Over recent decades, genetic and molecular research on methamphetamine use disorders has expanded considerably, yet a comprehensive synthesis of this growing body of literature is lacking. This study conducted a bibliometric analysis to map the scientific landscape of genetic and molecular biology research on methamphetamine use, identifying key contributors, influential publications, publication trends, and co-occurring keywords and citations. A systematic search of the Scopus database retrieved 1550 documents. After applying the inclusion criteria and manual screening, 449 peer-reviewed articles published between 1993 and 2025 were included. Performance analysis and scientific mapping were conducted using VOSviewer software through bibliographic coupling and keyword co-occurrence. The study followed the BIBLIO checklist for reporting bibliometric reviews in biomedical literature. Publication output increased markedly after 2005, peaking in 2022, followed by a decline that may reflect a shift in research priorities. The United States, China, and Japan emerged as leading contributors, underscoring their significant investment in addiction and molecular research. Keyword co-occurrence revealed strong emphasis on addiction, dopamine, neurotoxicity, gene expression, and genetic polymorphisms, highlighting their central role in the pathophysiology of methamphetamine use disorders. This bibliometric analysis demonstrates substantial growth and influence of genetic research on methamphetamine use. Despite a recent decline in publications, the field provides a solid foundation for future interdisciplinary research and funding priorities in addiction genetics. Full article

Melanoma is a highly heterogeneous disease, with unique genetic subtypes that influence clinical behavior and treatment response. While targeted therapies and immunotherapy have transformed care for more common types of melanoma, optimal strategies for KIT-mutant melanoma are less well-defined. In this review, we summarize the associations between KIT mutations and specific clinico-pathologic patterns, including their enrichment in acral, mucosal, and chronically sun-damaged melanomas. We detail the spectrum of KIT mutations across relevant exons, noting how mutation subtype influences sensitivity to targeted therapies. We will then analyze several therapeutic trials and case reports that describe the use of c-KIT inhibitors as well as immune checkpoint inhibitors in melanoma treatment. We also discuss early findings supporting combination strategies that may enhance therapeutic outcomes. Finally, we identify critical gaps in understanding the mechanisms of resistance, CNS progression, and the immunogenic landscape of KIT-driven melanoma. Deeper insight into the function of KIT and its interaction with therapeutic pathways is essential to optimizing treatment sequencing and tailoring personalized strategies that improve outcomes in this patient population. Full article

Citrus leaf blotch virus (CLBV) is a positive-sense single-stranded RNA virus belonging to the genus Citrivirus within the family Betaflexiviridae. It infects a broad range of economically significant fruit crops, including citrus, kiwifruit, and apple. Surveys conducted in the field have documented appreciable incidence rates in several hosts, thereby emphasizing its emerging threat to global pomiculture. Comprehensive surveillance of CLBV genetic diversity is indispensable for predicting strain-specific epidemics and designing durable, broadly protective control strategies. Current surveys of CLBV diversity are still gene-fragment-centric, with whole-genome resolution remaining largely untapped. In this study, an analysis of codon usage bias analysis was performed using all available CLBV full-length genomes. The findings revealed that CLBV exhibits low codon usage bias, with natural selection, rather than mutational drift, being the primary driver. Phylogenetic analysis has been demonstrated to categorize isolates according to their host of origin rather than their geographical location. This observation suggests that host adaptation may supersede spatial structure in CLBV evolution and reinforce natural selection as the dominant force shaping its codon usage landscape. From the perspective of the codon adaptation index, Prunus avium is the host that exerts the greatest influence on the formation of its codon usage bias. The present study provides the first genome-wide portrait of CLBV codon usage bias, offering a robust framework for future investigations into its origin and evolutionary dynamics. Full article

Online parameter tuning significantly enhances the performance of optimization algorithms by dynamically adjusting mutation and crossover rates. However, current approaches often suffer from high computational costs and limited adaptability to complex and dynamic fitness landscapes, particularly when machine learning methods are employed. This work proposes a quantized shallow neural network (SNN) as an efficient learning-based component for dynamically adjusting the mutation and crossover rates of a genetic algorithm (GA). By leveraging runtime-generated data and applying quantization techniques like Quantization-aware Training (QaT) and Post-training Quantization (PtQ), the proposed approach reduces computational overhead while maintaining competitive performance. Experimental evaluation on 15 continuous benchmark functions demonstrates that the quantized SNN achieves high-quality solutions while significantly reducing execution time compared to alternative shallow learning methods. This study highlights the potential of quantized SNNs to balance efficiency and performance, broadening the applicability of shallow learning in optimization. Full article

RNA methylation, particularly N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), functions as a pivotal post-transcriptional regulatory mechanism and plays a central role in plant growth, development, and stress responses. This review provides a systematic summary of recent advances in RNA methylation research in cucurbit crops. To date, high-throughput technologies such as MeRIP-seq and nanopore direct RNA sequencing have enabled the preliminary construction of RNA methylation landscapes in cucurbit species, revealing their potential regulatory roles in key agronomic traits, including fruit development, responses to biotic and abiotic stresses, and disease resistance. Nevertheless, this field remains in its early stages for cucurbit crops and faces several major challenges: First, mechanistic understanding is still limited, with insufficient knowledge regarding the composition and biological functions of the core protein families involved in methylation dynamics—namely, “writers,” “erasers,” and “readers.” Second, functional validation remains inadequate, as direct evidence linking specific RNA methylation events to downstream gene regulation and phenotypic outcomes is largely lacking. Third, resources are scarce; compared to model species such as Arabidopsis thaliana and rice, cucurbit crops possess limited species-specific genetic data and genetic engineering tools (e.g., CRISPR/Cas9-based gene editing systems), which significantly hampers comprehensive functional studies. To overcome these limitations, future research should prioritize the development and application of more sensitive detection methods, integrate multi-omics datasets—including transcriptomic and methylomic profiles—to reconstruct regulatory networks, and conduct rigorous functional assays to establish causal relationships between RNA methylation modifications and phenotypic variation. The ultimate objective is to fully elucidate the biological significance of RNA methylation in cucurbit plants and harness its potential for crop improvement through genetic and biotechnological approaches. Full article

Background: Trait convergence or parallelism is widely seen across the animal and plant kingdoms. For example, the evolution of eyes in cephalopods and vertebrate lineages, wings in bats and insects, or shark and dolphin body shapes are examples of convergent evolution. Such traits develop as a function of environmental pressures or opportunities that lead to similar outcomes despite the independent origins of underlying tissues, cells, and gene transcriptional patterns. Our current understanding of the molecular processes underlying these phenomena is gene-centric and focuses on how convergence involves the recruitment of novel genes, the recombination of gene products, and the duplication and divergence of genetic substrates. Scope: Despite the independent origins of a given trait, these model organisms still possess some form of epigenetic processes conserved in eukaryotes that mediate gene-by-environment interactions. These traits evolve under similar environmental pressures, so attention should be given to plastic molecular processes that shape gene function along these evolutionary paths. Key Mechanisms: Here, we propose that epigenetic processes such as histone-modifying machinery are essential in mediating the dialog between environment and gene function, leading to trait convergence across disparate lineages. We propose that epigenetic modifications not only mediate gene-by-environment interactions but also bias the distribution of de novo mutations and recombination, thereby channeling evolutionary trajectories toward convergence. An inclusive view of the epigenetic landscape may provide a parsimonious understanding of trait evolution. Full article

Androgenetic alopecia (AGA) is a prevalent, multifactorial hair disorder affecting a substantial portion of both males and females, with significant psychosocial consequences. Over the past decade, regenerative medicine has reshaped AGA treatment, offering biologically driven alternatives to conventional pharmacological and surgical therapies. Among these, Autologous Micrografting Technology (AMT) (Regenera Activa^® by Rigenera^® Technology, Barcelona, Spain) emerged 10 years ago as a notable innovation leveraging the body’s intrinsic regenerative potential through micrografts derived from a healthy scalp tissue. This review provides a comprehensive overview of the pathophysiology of AGA—including genetic, hormonal, and inflammatory contributors—and evaluates the clinical efficacy, safety, and mechanistic basis of AMT in comparison with other regenerative strategies such as platelet-rich plasma, adipose-derived mesenchymal stem cells, and exosome-based treatments. Clinical studies demonstrate that AMT yields significant short-term improvements in hair density and thickness with favorable safety outcomes. Moreover, advancements in device technology and treatment protocols have enhanced consistency and reproducibility. As multimodal and personalized approaches gain traction in hair restoration, AMT is a minimally invasive point-of-care procedure within the evolving regenerative landscape. Future studies are warranted to optimize treatment algorithms, extend follow-up data, better define patient selection criteria for maximizing outcomes with AMT, and expand the indication of autologous micrografting technology. Full article

Autosomal recessive (AR) disorders represent a significant public health challenge, as asymptomatic carriers are often unaware of their reproductive risks. This study provides the first comprehensive assessment of AR gene variant frequencies and their molecular landscape in a fertile Western Romanian population. Genetic results from 604 unrelated, unaffected Caucasian individuals of reproductive age, tested at a single genetic center between 2020 and 2024, were retrospectively analyzed. Next-generation sequencing (NGS) with a multi-gene panel targeting 300 AR-associated genes was used for molecular profiling. Variants were identified in 156 genes, with 75% of individuals carrying at least one AR variant (mean 1.77 variants/person). A subgroup with >3 pathogenic variants comprised 7.5%, posing a notable risk for future offspring. The most frequent variants were detected in HFE (1:5), CFTR (1:9), BTD (1:16), GJB2 (1:17), and CYP21A2 (1:19). Four variants (HFE, c.187C>G; BTD, c.1330G>C; CFTR, c.1210-34TG[11]T[5]; GALT, c.-119_-116del) were particularly prevalent, each exceeding 3% frequency. Considerable allelic heterogeneity was observed for distrinctive variants in CFTR (14), PAH (12), USH2A (12), and ATP7B (9). Several variants were linked to severe disorders, with CFTR, GALT, ATP7B, and SMN1 identified as “red zone” genes associated with high morbidity and mortality. Low-frequency variants formed a “long tail” (83.9%), reflecting marked population heterogeneity and potential hidden disease risks. The study reveals high allelic diversity and a strong prevalence of AR variants in Western Romania. Variant-based gene classification supports population-level screening, highlighting the public health value of a national program to identify carriers and prevent severe inherited disorders. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition globally, driven by strong genetic and environmental components. This review summarizes recent advances in understanding the genetic architecture of MASLD. Genome-wide association studies (GWAS) have identified several key risk variants, primarily in genes such as PNPLA3, TM6SF2, GCKR, and MBOAT7, which influence hepatic lipid metabolism and disease progression. By utilizing surrogate markers of MASLD, researchers have also identified numerous putative MASLD-associated genes, warranting further investigation through functional genomics approaches. Next-generation sequencing techniques have uncovered rare variants in genes like APOB and ABCB4, as well as protective variants in HSD17B13 and CIDEB. This review discusses the potential of polygenic risk scores for disease stratification and the development of genetically informed therapeutic strategies. Additionally, it explores the future of functional genomics approaches in discovering novel treatment strategies. While the evolving genetic landscape of MASLD provides promising insights for precision medicine approaches in diagnosis, prognosis, and treatment, significant translational gaps remain. Addressing these challenges will be critical for realizing the full potential of personalised approaches in clinical management. This review synthesizes these findings and discusses their implications for future research and clinical practice in MASLD. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations. Full article

Metastasis is the leading cause of cancer-related mortality, representing a highly coordinated, multistep process in which malignant cells gain the ability to invade, survive in the circulation, and establish secondary tumors at distant sites. While genetic mutations initiate oncogenesis, accumulating evidence shows that epigenetic and epitranscriptomic regulators, encompassing DNA methylation, RNA modifications, and noncoding RNAs (ncRNAs), reshape metastatic phenotypes. This review integrates current insights into these mechanisms and their crosstalk, with a primary focus on their methylation modification. Given their plasticity and potential reversibility, these regulators are attractive targets for therapeutic intervention. Defining the dynamic interplay between DNA and RNA modifications and ncRNAs provides a coherent framework for controlling metastasis and guides the development of precision epigenetic strategies and biomarkers. Future research that integrates multi-omics approaches and spatial transcriptomics will be essential for revealing the epigenetic and epitranscriptomic layers of the metastatic landscape. Full article

Background: Ampullary cancer is a rare biliary tract cancer arising from one of the three epithelial tissues in the region. Leveraging a large patient-level genomic database, this study aims to identify, explore, and describe the genetic landscape of ampullary carcinoma and its implications. Methods: A retrospective analysis of ampullary cancer samples was conducted using the AACR Project GENIE database. Analysis of recurrent somatic mutations at large and between patient populations, and co-occurrence and mutual exclusivity of mutations was conducted, with a p-value < 0.05. Results: The most frequent mutations were identified as TP53 (53.2%), KRAS (46.6%), and SMAD4 (16.6%). Mutational differences were noted between sexes, White vs. Non-white groups, and histopathological subtypes. Significant mutual exclusivity was found between KRAS and ERBB2. Co-occurrence was observed in the ARID1A mutation with KMT2D, ERBB2, and PIK3CA; CDKN2A with the SMAD4 and KRAS mutations; TP53 mutation with the CTNNB1 mutation; and KRAS co-occurred with an APC mutation. Reduced survival rates were seen in populations with the TP53 or KRAS mutation. Conclusions: This study provides a detailed descriptive genomic landscape of ampullary carcinoma, highlighting frequent mutations between patient groups and the mutational burden of the DNA damage response pathway in ampullary cancer, laying important groundwork for the development of therapeutic targets and more individualized treatment regimens. Full article

Myelodysplastic neoplasms (MDS) are characterized by remarkable heterogeneity in clinical manifestations, posing significant management challenges arising due to genetic plasticity. While the Revised International Prognostic Scoring System (IPSS-R) has traditionally stratified MDS into higher-risk (HR) and lower-risk (LR) categories, the recently developed Molecular International Prognostic Scoring System (IPSS-M) integrates molecular signatures and has further enhanced prognostic stratification. In LR-MDS, current therapeutic interventions remain non-curative and the goal of treatment is centered along three critical axes: reducing transfusion dependence, improving quality of life, and reducing the risk of progression to acute myeloid leukemia (AML). This review examines recent progress made in the therapeutic landscape of LR-MDS, with particular emphasis on the molecular basis of these novel agents that may have disease-modifying potential. We evaluate the clinical trials and targeted agents in the pipeline for treating LR-MDS, providing a comprehensive perspective where these treatment modalities are placed in the current standard of care and how these novel targets can shape future therapeutic innovations. Full article