Search Results (673)

Simian foamy virus (SFV) is a retrovirus that infects primates. However, epidemiological studies of SFV are often limited to captive populations. The southeastern Brazilian Atlantic Forest is home to both an endemic, endangered species, Leontopithecus rosalia, and an introduced species, Leontopithecus chrysomelas, to which no data on SFV exist. In this study, we assessed the molecular prevalence of SFV, their viral load, and their phylogenetic relationship in these two species of primates. Genomic DNA was extracted from 48 oral swab samples of L. chrysomelas and 102 of L. rosalia. Quantitative PCR (qPCR) was performed to diagnose SFV infection and quantify viral load. SFV prevalence was found to be 23% in L. chrysomelas and 33% in L. rosalia. No age-related differences in prevalence were observed; however, L. rosalia showed a higher mean viral load (3.27 log10/10⁶ cells) compared to L. chrysomelas (3.03 log10/10⁶ cells). The polymerase gene sequence (213 pb) of L. rosalia (SFVlro) was clustered within a distinct SFV lineage found in L. chrysomelas. The estimated origin of SFVlro dated back approximately 0.0836 million years ago. Our study provides the first molecular prevalence data for SFV in free-living Leontopithecus populations while offering insights into the complex evolutionary history of SFV in American primates. Full article

The goal of phylogeography is to explain how microevolutionary forces shape the gene pool of a lineage into the geography. In this study we have evaluated the amount of genetic variation in 13 populations of Dorymyrmex bicolor distributed in a mountainous region in Central Veracruz, Mexico. To do so, we sequenced fragments from the mitochondrial COI, COII, and nuclear LWRh genes. Segregated sites were found only at the mitochondrial markers, recovering a total of 21 different haplotypes. The nucleotide diversity ranged from 0 to 0.5% at the different sampling sites. Phylogenetic and spatial analyses of molecular variance revealed a weak but significant phylogeographic structure associated with lowland and mountainous zones. Molecular clock analysis suggests that radiation in the mountain area started 7500 years ago, whereas lineage radiation in the lowland started more recently, around 2700 years ago. The phylogeographic structure is incipient, with nests from lowlands more closely related to mountain nests than to other lowland nests, and vice versa. This seems to be consistent with a model of incomplete lineage sorting. The obtained patterns appear to be the result of restricted gene flow mediated by a complex topographic landscape that has been shaped by a dynamic geologic history. Full article

Chemical modifications are the standard for small interfering RNAs (siRNAs) in therapeutic applications, but predicting their off-target effects remains a significant challenge. Current approaches often rely on sequence-based encodings, which fail to fully capture the structural and protein–RNA interaction details critical for off-target prediction. In this study, we developed a framework to generate reproducible structure-based chemical features, incorporating both molecular fingerprints and computationally derived siRNA–hAgo2 complex structures. Using an RNA-Seq off-target study, we generated over 30,000 siRNA–gene data points and systematically compared nine distinct types of feature representation strategies. Among the datasets, the highest predictive performance was achieved by Dataset 3, which used extended connectivity fingerprints (ECFPs) to encode siRNA and mRNA features. An energy-minimized dataset (7R), representing siRNA–hAgo2 structural alignments, was the second-best performer, underscoring the value of incorporating reproducible structural information into feature engineering. Our findings demonstrate that combining detailed structural representations with sequence-based features enables the generation of robust, reproducible chemical features for machine learning models, offering a promising path forward for off-target prediction and siRNA therapeutic design that can be seamlessly extended to include any modification, such as clinically relevant 2′-F or 2′-OMe. Full article

The selective regulation of gene expression at the RNA level represents a rapidly evolving field offering substantial clinical potential. This review examines the molecular mechanisms of intracellular enzymatic systems that utilize single-stranded nucleic acids to downregulate specific RNA targets. The analysis encompasses antisense oligonucleotides and synthetic mimics of small interfering RNA (siRNA), microRNA (miRNA), transfer RNA-derived small RNA (tsRNA), and PIWI-interacting RNA (piRNA), elucidating their intricate interactions with crucial cellular machinery, specifically RNase H1, RNase P, AGO, and PIWI proteins, mediating their biological effects. The functional and structural characteristics of these endonucleases are examined in relation to their mechanisms of action and resultant therapeutic outcomes. This comprehensive analysis illuminates the interactions between single-stranded nucleic acids and their endonuclease partners, covering antisense inhibition pathways as well as RNA interference processes. This field of research has important implications for advancing targeted RNA modulation strategies across various disease contexts. Full article

This study is based on the whole gene resequencing data of 162 individuals from 16 chicken breeds. We calculated the historical effective population size (Ne), differentiation time and genetic hybridization degree of the population to understand its historical dynamics, in order to provide a theoretical basis for the scientific protection and utilization of the germplasm resources of Baicheng Oil Chicken (BCY). The main results are as follows: using SMC++ and fastsimcoal2 software, respectively, we estimated Ne of BCY at 46,066 in the past and inferred a divergence time of 428–548 years ago. D-statistical analysis revealed a ~7% genetic introgression from White Leghorn chicken (LH) to BCY. Notably, infiltration genes such as CTNNAL1 (potentially influencing egg production) and RARX (possibly associated with fat deposition) were identified. These findings provide insights into BCY’s demographic history and support its genetic conservation and utilization. Full article

Fusarium oxysporum f. sp. vasinfectum (Fov) is a devastating cotton pathogen. Australian Fov strains are distinguished by their ability to infect plants without nematode interaction and are genetically distinct from global Fov, classified into two vegetative compatibility groups (VCG-01111 and VCG-01112). Here, we present chromosome-level genome assemblies of a historical isolate for each Australian Fov VCG. The end-to-end gapless genome assemblies demonstrate high contiguity and completeness, with 97.7% BUSCO completeness for both isolates. Phylogenetic analysis indicates that the Australian Fov lineages diverged from other known Fov genomes over 3.6 million years ago, while VCG-01111 and VCG-01112 separated approximately 1.1 million years ago. Comparative genomics analysis identified four accessory chromosomes unique to the Australian isolates. Functional annotations revealed 14,495 and 15,342 genes in VCG-01111 and VCG-01112, respectively, with accessory chromosomes containing significantly fewer genes than core chromosomes. Ortholog analysis uncovered unique gene clusters enriched in key metabolic pathways, pathogenicity, and cell division processes. Additionally, we identified several novel lineage-specific peptides unique to each Australian isolate. This comprehensive genomic characterization provides the first insights into the unique evolutionary history of Australian Fov, distinguishing them from global Fov races. Our findings lay the foundation for understanding the genetic factors underlying their exceptional virulence, which makes Australian Fov among the most aggressive cotton pathogens worldwide. Full article

APOL1 is the most recent member of the APOL gene family and is expressed exclusively in humans and a few higher primates. More than twenty years ago, it was discovered that APOL1 protects humans from infections by trypanosome subspecies that cause African sleeping sickness. Interestingly, by a co-evolutionary process between parasite and host, two APOL1 variants emerged, which, in addition to their trypanotoxic effects, are simultaneously associated with a significantly increased risk for various different kidney diseases, which are now summarized as APOL1-mediated kidney diseases (AMKDs). The aim of this review is to highlight and formulate key aspects of APOL1’s cell biologic features, including questions and unaddressed aspects. This perspective may contribute to a deeper understanding of APOL1-associated cytotoxicity as well as AMKDs. Full article

Myocardial injury is a critical determinant of prognosis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, its underlying mechanisms remain incompletely understood. In this study, we examined the effects of SARS-CoV-2-derived RNA fragments on human cardiomyocytes. We identified a 19-nucleotide sequence within the viral genome that shares complete sequence homology with the human F1F0 ATP synthase subunit alpha gene (ATP5A). This sequence was found to associate with Argonaute 2 (AGO2) and downregulate ATP5A expression via a mechanism analogous to RNA interference. Consequently, oxidative phosphorylation was suppressed in cardiomyocytes, leading to impaired myocardial maturation and the emergence of heart failure-like phenotypes. Notably, exosome-mimetic liposomal delivery of this RNA fragment to cardiomyocytes reproduced the ATP5A-suppressive effect. These findings suggest that SARS-CoV-2-derived RNA fragments may contribute to myocardial injury through the siRNA-like modulation of mitochondrial gene expression. Further validation in animal models and patient-derived materials is warranted. Full article

RNA silencing regulates diverse cellular processes in plants. Argonaute (AGO), Dicer-like (DCL), and RNA-dependent RNA polymerase (RDR) proteins are core components of RNA interference (RNAi). Despite their functional significance, the systematic identification and characterization of these families have remained largely unexplored in Siraitia grosvenorii. Using HMMER and Pfam analyses, we identified six SgAGO, four SgDCL, and six SgRDR genes. Phylogenetic analysis classified SgAGOs, SgDCLs, and SgRDRs into five, four, and four clades, respectively, all of which clustered closely with homologs from other Cucurbitaceae species, demonstrating lineage-specific evolutionary conservation. Promoter cis-element analysis revealed the significant enrichment of hormonal (methyl jasmonate, abscisic acid) and stress-responsive (light, hypoxia) elements, indicating their roles in environmental adaptation. Tissue-specific expression profiling showed that most SgAGO, SgDCL, and SgRDR genes were highly expressed in flowers and mid-stage fruits (35 days after pollination), while SgAGO10.1 exhibited stem-specific expression. By contrast, SgRDR1.2 displayed no tissue specificity. Notably, sex-biased expression patterns in dioecious flowers suggested the RNAi-mediated regulation of gametophyte development and their potential roles in reproductive and secondary metabolic processes. This study lays the foundation for further exploration of RNAi machinery’s role in coordinating mogroside biosynthesis and stress resilience in S. grosvenorii while providing potential targets for genetic improvement. Full article

Delta-9-tetrahydrocannabinol (Δ-9-THC or THC), the primary psychoactive constituent of cannabis, can lead to adverse health conditions, including mental health issues, brain impairment, and cardiac and respiratory problems. The amount of THC in cannabis has steadily climbed over the past few decades, with today’s cannabis having three times the concentration of THC compared to 25 years ago. Inhalation is a major route of exposure, allowing substances to enter the body via the respiratory tract. THC exposure causes cell death in the airway epithelium; however, the molecular underpinning of THC exposure-induced bronchial epithelial cell death is not clearly understood. To address the mechanisms involved in this process, the present study examined the cell viability, oxidative stress, lipid peroxidation, and transcriptional alterations caused by various concentrations of Δ-9-THC (0, 800, 1000, 1200, and 1500 ng/mL) in a human bronchial epithelial cell line (BEAS-2B) in vitro. Δ-9-THC exposure caused a significant dose-dependent decrease in cell viability after 24 h exposure. Transcriptome analysis showed a distinct dose-dependent response. HIF-1 signaling, ferroptosis, AMPK signaling, and immunogenic pathways were activated by Δ-9-THC-upregulated genes. Glutathione and fatty acid metabolic pathways were significantly altered by Δ-9-THC-dependent downregulated genes. Ingenuity Pathway Analysis (IPA) revealed several top canonical pathways altered by Δ-9-THC exposure, including ferroptosis, NRF-2-mediated oxidative stress response, caveolar-mediated endocytosis (loss of cell adhesion to the substrate), tumor microenvironment, HIF1alpha signaling, and the unfolded protein response pathway. Δ-9-THC-induced cell death was ameliorated by inhibiting the ferroptosis pathway, whereas treatments with ferroptosis agonist exacerbated the cell death process, suggesting that Δ-9-THC-induced bronchial epithelial cell death potentially involves the ferroptosis pathway. Full article

Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered “undruggable”. In recent years, however, several promising strategies have emerged, including the enhanced iterations of previous approaches and novel techniques aimed at targeting proteins that have traditionally been considered undruggable. There is a growing interest in small molecules that can restore the tumor-suppressive functions of mutant p53 proteins, and the development of drugs specifically designed for particular p53 mutation types is currently underway. Other approaches aim to deplete mutant p53 or exploit vulnerabilities associated with its expression. Additionally, genetic therapy strategy and approaches have rekindled interest. Advances in mutant p53 biology, compound mechanisms, treatment modalities, and nanotechnology have opened up new avenues for p53-based therapies. However, significant challenges remain in clinical development. This review reassesses the progress in targeting p53-mutant cancers, discusses the obstacles in translating these approaches into effective therapies, and highlights p53-based therapies via nanotechnology. Full article

Auricularia mushrooms, common bulk edible fungi, have considerable culinary and medicinal value. The Qinling region, represented by Zhashui County, is the main production area of Auricularia mushrooms in China. In this study, two wild Auricularia strains, M12 and M13, selected from the Qinling region for their desirable horticultural traits after domestication, were sequenced and characterized. Sequencing assembly results based on Illumina NovaSeq and PacBio Sequel II HiFi showed that the M12 genome was 56.04 Mbp in size, with 2.58% heterozygosity and 14.13% repetitive sequences, and was anchored on 12 chromosomes using HI-C technology. In contrast, the M13 genome was 52.10 Mbp, showed 2.34% heterozygosity, 13.89% repetitive sequences, and was assembled into 12 scaffolds. Collinearity analysis revealed extensive homologous regions between the M12 and M13 genomes. Phylogenetic analysis suggested that the divergence between M12 and M13 occurred approximately 4.575 million years ago (MYAs), while their divergence from Auricularia subglabra TFB-10046 SS5 occurred approximately 33.537 MYAs. Analyses of CYP450, carbohydrate-active enzymes (CAZymes), and gene family expansion/contraction revealed distinct genomic features between the two strains. SSR and LTR insertion time analyses revealed the genome dynamics of the two strains during their evolution. Analysis of secondary metabolite-associated biosynthetic gene clusters (BGCs) provides powerful clues to understand the origin of bioactive compounds in the Auricularia mushroom. This work represents the first genome sequencing of the Auricularia species derived from the Qinling region. These results not only enriched our understanding of the Auricularia genome but also provided an important genomic resource and theoretical basis for the subsequent genetic breeding, functional gene mining, and development of medicinal components of Auricularia species. Full article

Rice (Oryza sativa) is one of the key staple crops, providing food for nearly half of the world’s population. The past twenty years have seen significant advances in understanding Oryza species through genome sequencing efforts. However, the stability of Oryza genomes during their divergence has not been well characterized. Here, by performing gene collinearity and comparative genomics analysis, we selected ten Oryza species and three other Poaceae species to check their genome stability, with Leersia perrieri as the reference. Intra- and intergenomic analysis showed a ~30% difference in homologous block numbers and a 35.7% difference in collinear gene numbers per block, indicating that Oryza genomes have undergone extensive DNA permutations. Notably, we found that Oryza chromosomes with smaller ordinal numbers have often preserved larger percentages of genes, while those with bigger numbers have undergone more gene losses. This unique observation may be explained by elevated gene losses incurred by illegitimate or homoeologous recombination between homoeologous chromosomes produced by the grass-common tetraploidization (GCT) ~100 million years ago (Mya), e.g., Chro. 11 and 12. However, the lowered gene loss rates in Chro. 1–3 could be explained by earlier restriction of illegitimate recombination after the GCT due to there often being (larger) neo-chromosomes produced by the fusion of ancestral chromosomes. The enriched NBS-LRR (nucleotide-binding site and leucine-rich repeat) genes in chromosomes 11 and 12 are another explanation for the above observation. Further evidence was obtained from other Poaceae plants. Moreover, we revealed around twice as many differences in tandem genes and their densities among Oryza plants, further showing their divergent levels of genome stability. The present efforts may contribute to the understanding of the stability of the Oryza genome and its formation, evolution, and functional innovation. Full article

So far, synthetic biology approaches for the construction of artificial microorganisms have fostered the transformation of acceptor cells with genomes from donor cells. However, this strategy seems to be limited to closely related bacterial species only, due to the need for a “fit” between donor and acceptor proteomes and structures. “Fitting” of cellular regulation of metabolite fluxes and turnover between donor and acceptor cells, i.e. cybernetic heredity, may be even more difficult to achieve. The bacterial transformation experiment design 1.0, as introduced by Frederick Griffith almost one century ago, may support integration of DNA, macromolecular, topological, cybernetic and cellular heredity: (i) attenuation of donor Pneumococci of (S) serotype fosters release of DNA, and hypothetically of non-DNA structures compatible with subsequent transfer to and transformation of acceptor Pneumococci from (R) to (S) serotype; (ii) use of intact donor cells rather than of subcellular or purified fractions may guarantee maximal diversity of the structural and cybernetic matter and information transferred; (iii) “Blending” or mixing and fusion of donor and acceptor Pneumococci may occur under accompanying transfer of metabolites and regulatory circuits. A Griffith transformation experiment design 2.0 is suggested, which may enable efficient exchange of DNA as well as non-DNA structural and cybernetic matter and information, leading to unicellular hybrid microorganisms with large morphological/metabolic phenotypic differences and major features compared to predeceding cells. The prerequisites of horizontal gene and somatic cell nuclear transfer, the molecular mechanism of transformation, the machineries for the biogenesis of bacterial cytoskeleton, micelle-like complexes and membrane landscapes are briefly reviewed on the basis of underlying conceptions, ranging from Darwin’s “gemmules” to “stirps”, cytoplasmic and “plasmon” inheritance, “rhizene agency”, “communicology”, “transdisciplinary membranology” to up to Kirschner’s “facilitated variation”. Full article

Clostridium butyricum Argonaute (CbAgo) can achieve DNA-guided DNA recognition and cleavage at physiological temperatures (~37 °C), making it a promising tool for gene editing. However, its significant off-target effects, particularly associated with the seed region (sites 2–8), pose challenges for precise gene therapy. This study focuses on enhancing the specificity of the seed region recognition to mitigate these off-target effects. We investigated the molecular recognition process between the CbAgo-gDNA complex and the seed region of the target DNA using molecular dynamics simulations and automated path searching. Our findings reveal that positively charged residues located in an α-helix domain at the DNA–protein interface (R279, H285, K287, K288, K291, K298) facilitate rapid binding to the DNA phosphate backbone. Such interaction enhances the pre-formation of the DNA double helix, reducing the reliance on base complementarity during duplex pairing. Further simulations showed that alanine replacement of these positively charged residues led to significantly improved sequence specificity for the target DNA seed region. Collectively, these results offered critical insights into the origin of off-target recognition by CbAgo in its seed region, shedding lights on its fidelity enhancement. Full article