Search Results (46,286)

Transfer-RNA-derived fragments (tRFs) are a novel class of small non-coding RNAs that have been implicated in oncogenesis. tRFs may act as post-transcriptional regulators by recruiting AGO proteins and binding to highly complementary regions of mRNA at seed regions, resulting in the knockdown of the transcript. Therefore, tRFs may be critical to tumorigenesis and warrant investigation as potential biomarkers. Meanwhile, the incidence of papillary thyroid carcinoma (PTC) has increased in recent decades and current diagnostic technology stands to benefit from new detection methods. Although small non-coding RNAs have been studied for their role in oncogenesis, there is currently no standard for their use as PTC biomarkers, and tRFs are especially underexplored. Accordingly, we aim to identify dysregulated tRFs in PTC that may serve as biomarker candidates. We identified dysregulated tRFs and driver genes between PTC primary tumor samples (n = 511) and adjacent normal tissue samples (n = 59). Expression data were obtained from MINTbase v2.0 and The Cancer Genome Atlas. Dysregulated tRFs and genes were analyzed in tandem to find pairs with anticorrelated expression. Significantly anticorrelated tRF-gene pairs were then tested for potential binding affinity using RNA22—if a heteroduplex can form via complementary binding, this would support the hypothesized RNA silencing mechanism. Four tRFs were significantly dysregulated in PTC tissue (p < 0.05), with only AsnGTT 3′-tRF being upregulated. Binding affinity analysis revealed that tRF-30-RY73W0K5KKOV (AsnGTT 3′-tRF) exhibits sufficient complementarity to potentially bind to and regulate transcripts of SLC26A4, SLC5A8, DIO2, and TPO, which were all found to be downregulated in PTC tissue. In the present study, we identified dysregulated tRFs in PTC and found that AsnGTT 3′-tRF is a potential post-transcriptional regulator and biomarker. Full article

Chlamydia trachomatis (CT) is a bacterium that causes one of the most common sexually transmitted infections (STIs) worldwide. In Panama, the prevalence of genital Chlamydia trachomatis (CT) among adolescents is 15.8%. However, no data describing circulating CT genotypes or evaluating molecular resistance are available. This study aims to determine the genotypes of genital CT infections and explore the macrolide resistance-associated mutations in this population to contribute to baseline information about CT circulating strains and antimicrobial resistance. Genomic analysis was performed on CT-positive, first-void urine specimens from school-going adolescents (14–19 years) in urban regions in Panama. The ompA gene was used for genotype and phylogenetic analysis, and the rplD, rplV, and 23S rRNA genes were used for molecular resistance analysis. Five genotypes were found: D, 15 (47%); F, 9 (28%); E, 4 (13%); Ia, 2 (6%); and Ja, 2 (6%) genotype Ja. A triple mutation (G52S, R65C, and V77A) was found in the rplV gene, though no mutations of interest were found for the rplD and 23S rRNA genes. The present study indicated CT genotype D had increased circulation within the population; mutations indicative of macrolide resistance were not found. Follow-up studies and implementation of active surveillance are necessary to understand the circulation of CT in Panama. Full article

Codon usage bias refers to the preferential use of synonymous codons, a widespread phenomenon found in bacteria, plants, and animals. Codon bias varies among species, families, and groups within kingdoms and between genes within an organism. Codon usage bias (CUB) analysis sheds light on the evolutionary dynamics of various species and optimizes targeted gene expression in heterologous host plants. As a significant order of gymnosperms, species within Gnetales possess extremely high ecological and pharmaceutical values. However, comprehensive analyses of CUB within the chloroplast genomes of Gnetales species remain unexplored. A systematic analysis was conducted to elucidate the codon usage patterns in 13 diverse Gnetales species based on the chloroplast genomes. Our results revealed that chloroplast coding sequences (cp CDSs) in 13 Gnetales species display a marked preference for AT bases and A/T-ending codons. A total of 20 predominantly high-frequency codons and between 2 and 7 optimal codons were identified across these species. The findings from the ENC-plot, PR2-plot, and neutrality analyses suggested that both mutation pressure and natural selection exert influence on the codon bias in these 13 Gnetales species, with natural selection emerging as the predominant influence. Correspondence analysis (COA) demonstrated variation in the codon usage patterns among the Gnetales species and indicated mutation pressure is another factor that could impact CUB. Additionally, our research identified a positive correlation between the measure of idiosyncratic codon usage level of conservatism (MILC) and synonymous codon usage order (SCUO) values, indicative of CUB’s potential influence on gene expression. The comparative analysis concerning codon usage frequencies among the 13 Gnetales species and 4 model organisms revealed that Saccharomyces cerevisiae and Nicotiana tabacum were the optimal exogenous expression hosts. Furthermore, the cluster and phylogenetic analyses illustrated distinct patterns of differentiation, implying that codons, even with weak or neutral preferences, could affect the evolutionary trajectories of these species. Our results reveal the characteristics of codon usage patterns and contribute to an enhanced comprehension of evolutionary mechanisms in Gnetales species. Full article

Rhizoctonia large patch (Rhizoctonia solani AG2-2 LP) significantly reduces turfgrass quality, aesthetics, and playability. Synthetic fungicides are commonly used for managing this disease, but they present high costs, potential for fungicide resistance, and environmental concerns. We conducted in vitro assays to test the effectiveness of three biofungicides, seven synthetic fungicides, and ten combinations against R. solani. We then assessed seven spray programs that included Bacillus subtilis QST713 and propiconazole, either alone or tank-mixed, on zoysiagrass ‘El Toro’ in a growth chamber and in field trials. Biofungicide B. subtilis QST713 reduced pathogen growth by up to 100% in vitro. B. subtilis QST713 alone or combined with synthetic fungicides and/or in rotation was as effective as the standalone synthetic fungicide, reducing disease severity and AUDPC by 81 and 77% (growth chamber) and by 71 and 52% (field), respectively, while maintaining acceptable turfgrass quality. Additionally, we screened zoysiagrass genotypes and advanced breeding lines against three R. solani isolates in growth chamber studies. Five genotypes and two breeding lines demonstrated resistance to Rhizoctonia large patch across isolates, highlighting their potential for developing disease-resistant cultivars. Our findings suggest that integrating biofungicides, resistant cultivars with chemical controls offer sustainable and effective strategies for managing Rhizoctonia large patch Full article

The presence of antibiotic-resistant Escherichia coli in food is a serious and persistent problem worldwide. In this study, 68 E. coli strains isolated from Thai food samples were characterized. Based on antibiotic susceptibility assays, 31 of these isolates (45.59%) showed multiple antibiotic resistance (MAR) index values > 0.2, indicating high exposure to antibiotics. Among these, strain CM24E showed the highest resistance (it was resistant to ten antibiotics, including colistin and imipenem). Based on genome sequencing, we identified four isolates (namely, CF25E, EF37E, NM10E1, and SF50E) with novel Achtman-scheme multi-locus sequence types (STs) (ST14859, ST14866, ST14753, and ST14869, respectively). Clermont phylogrouping was used to subtype the 68 researched isolates into five Clermont types, mainly A (51.47%) and B1 (41.18%). The bla_EC gene was found only in Clermont type A, while the bla_EC-13 gene was predominant in Clermont type B1. A correlation between genotypes and phenotypes was found only in Clermont type B1, which showed a strong positive correlation between the presence of an afa operon and yersiniabactin-producing gene clusters with the colistin resistance phenotype. Strain SM47E1, of Clermont type B2, carried the highest number of predicted virulence genes. In summary, this study demonstrates the pressing problems posed by the prevalence and potential transmission of antimicrobial resistance and virulence genes in the food matrix. Full article

R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA upon the collision of replication forks with transcription complexes. These RNA–DNA hybrids facilitate several transcriptional processes in the cell and have been described extensively in the literature. Recently, evidence has emerged that R-loops are key regulators of DNA tumor virus transcription and the replication of their lifecycle. Studies have demonstrated that R-loops on the Human Papillomavirus (HPV) genome must be resolved to maintain genome maintenance and avoid viral integration, a hallmark of HPV cancers. For Epstein–Barr virus (EBV), R-loops are formed at the oriLyt to establish lytic replication. Structural maintenance of chromosome proteins 5/6 (SMC5/6) bind to these viral R-loops to repress EBV lytic replication. Most viruses in the herpesvirales order, such as KSHV, contain R-loop-forming sequences. In this perspective, we will describe the current, although limited, literature demonstrating the importance of RNA–DNA hybrids to regulate DNA virus transcription. We will also detail potential new areas of R-loop research and how these viruses can be used as tools to study the growing field of R-loops. Full article

Repeating sequences of DNA, or repetitive elements (REs), are common features across both prokaryotic and eukaryotic genomes. Unlike many of their protein-coding counterparts, the functions of REs in host cells remained largely unknown and have often been overlooked. While there is still more to learn about their functions, REs are now recognized to play significant roles in both beneficial and pathological processes in their hosts at the cellular and organismal levels. Therefore, in this review, we discuss the various types of REs and review what is known about their evolution. In addition, we aim to classify general mechanisms by which REs promote processes that are variously beneficial and harmful to host cells/organisms. Finally, we address the emerging role of REs in cancer, aging, and neurological disorders and provide insights into how RE modulation could provide new therapeutic benefits for these specific conditions. Full article

Background and Objectives: Alopecia areata (AA) is a tissue-specific immune-mediated disorder that affects hair follicles and the nail apparatus. Due to the collapse of hair follicle immune privilege in AA, hair loss ranges in severity from small, localized patches on the scalp to the loss of entire body hair. Although AA is of uncertain etiology, the disease has a common genetic basis with a number of other autoimmune diseases. Materials and Methods: To identify candidate genes that confer susceptibility to AA in the Jordanian population and further understand the disease background, we performed DNA genotyping using case–control samples of 152 patients and 150 healthy subjects. Results: While no significant result was observed in the ten single-nucleotide polymorphisms (SNPs), CLEC4D rs4304840 variants showed significant associations with AA development within our cohort (p = 0.02). The strongest associations were for the codominant and recessive forms of rs4304840 (p = 0.023 and p = 0.0061, respectively). Conclusions: These findings suggest that CLEC4D gene variants may contribute to AA pathogenesis among Jordanians. Further advanced genetic analysis and functional investigations are required to elucidate the genetic basis of the disease. Full article

Antimicrobial resistance (AMR) surveillance in fecal Escherichia coli isolates from wildlife is crucial for monitoring the spread of this microorganism in the environment and for developing effective AMR control strategies. Wildlife can act as carriers of AMR bacteria and spread them to other wildlife, domestic animals, and humans; thus, they have public health implications. A total of 128 Escherichia coli isolates were obtained from 66 of 217 fecal samples obtained from different wild animals using media without antibiotic supplementation. Antibiograms were performed for 17 antibiotics to determine the phenotypic resistance profile in these isolates. Extended-spectrum β-lactamase (ESBL) production was tested using the double-disc synergy test, and 29 E. coli strains were selected for whole genome sequencing. In total, 22.1% of the wild animals tested carried multidrug-resistant E. coli isolates, and 0.93% (2/217) of these wild animals carried E. coli isolates with ESBL-encoding genes (bla_CTX-M-65, bla_CTX-M-55, and bla_EC-1982). The E. coli isolates showed the highest resistance rates to ampicillin and were fully susceptible to amikacin, meropenem, ertapenem, and imipenem. Multiple resistance and virulence genes were detected, as well as different plasmids. The relatively high frequency of multidrug-resistant E. coli isolates in wildlife, with some of them being ESBL producers, raises some concern regarding the potential transmission of antibiotic-resistant bacteria among these animals. Gaining insights into antibiotic resistance patterns in wildlife can be vital in shaping conservation initiatives and developing effective strategies for responsible antibiotic use. Full article

Exopolysaccharides (EPSs) produced by microorganisms play an important role in biotolerance and reducing heavy metal (HM) contamination by limiting the migration of HMs into plants. However, research on the application of EPS-producing marine bacteria for soil heavy metal remediation remains limited, particularly regarding their mechanisms of HM immobilization in soil and impact on plant growth. In this study, the EPS-producing marine bacterium Micrococcus antarcticus HZ was investigated for its ability to immobilize Pb and produce EPSs in soil filtrate. The effects on the growth quality and biomass of pakchoi (Brassica chinensis L.), as well as bacterial communities in inter-root soil contaminated with Pb, were also investigated. The results indicated that HZ could reduce the Pb concentration in the soil filtrate, achieving a removal rate of 43.25–63.5%. The EPS content and pH levels increased in the presence of Pb. Pot experiments showed that adding HZ significantly increased the biomass of pakchoi (9.45–14.69%), vitamin C (Vc) (9.69–12.92%), and soluble protein content (22.58–49.7%). HZ reduced the Pb content in the roots (17.52–47.48%) and leaves (edible tissues) (43.82–52.83%) of pakchoi. HZ increased soil enzyme activities (alkaline phosphatase, dehydrogenase, and urease), and the contents of ammonium nitrogen and nitrate nitrogen. Additionally, HZ also increased the relative abundance of beneficial bacteria (e.g., Proteobacteria, Cyanobacteria, and Chlorobacteria) in the inter-root soil, which have prophylactic and heavy-metal fixation functions. In summary, HZ reduces effective Pb content in edible tissues, roots, and inter-root soil by regulating inter-root soil microbial community structure, increasing soil pH, nitrogen content, and soil enzyme activity, and altering dominant phylum abundance. Full article

Background and objectives: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections, with non-infectious complications such as granulomatous–lymphocytic interstitial lung disease (GLILD) affecting up to 30% of patients. Methods: Using high-throughput 16S rRNA gene sequencing, salivary, sputum, and fecal microbiome from CVID patients with GLILD, comparing them to CVID patients without GLILD—with immune dysregulation (dCVID) and only infections (iCVID)—and healthy controls was analyzed. Results: A total of 41 CVID patients, 7 with GLILD, and 15 healthy donors were included. Global fecal biodiversity was significantly lower in GLILD patients compared to CVID subgroups and controls. GLILD patients harbored different specific bacterial communities in all niches, with some keystone species common to dCVID. Conchiformibius, Micrococcales, and Capnocytophaga are more frequent in the sputum of GLILD patients. Saliva in GLILD shows higher frequencies of Conchiformibius and Haemophilusparainfluenzae. Fecal samples from GLILD patients have higher levels of Gemella morbilorum, Lacticaseibacillus, and Cellulosimicrobium. A non-assigned Conchiformibius spp. is consistently associated with GLILD across different niches and could be a potential pathobiont or relevant microbiological marker for GLILD. Cluster network and correlation analyses show profound dysbiosis in the sputum, saliva, and feces of GLILD patients. Conclusions: These findings highlight significant microbiome alterations in CVID patients with GLILD, particularly in the respiratory tract, suggesting a possible link to both local and systemic immune dysregulation. Full article

Increasing consumption of apples (Malus domestica Borkh.) produced in Norway requires the availability of superior cultivars and extended marketability. Favorable texture and slow softening are important traits for consumer appreciation and postharvest performance. Apple texture has been well characterized using both sensory evaluation and instrumental assessments, and major quantitative trait loci (QTL) have been detected. With texture being targeted as an important trait and markers being publicly available, marker-assisted selection has already been implemented into several breeding programs. When focusing solely on a limited set of markers linked to well-investigated major QTLs, most minor-effect QTLs are normally excluded. To find novel potential SNP markers suitable to assist in selection processes, we selected a subset of accessions from a larger apple collection established in Norway based on the favorable alleles of two markers previously associated with texture, enabling the investigation of a minor part of the variance initially masked by the effect of major loci. The subset was employed to conduct a genome-wide association study aiming to search for associations with texture dynamics and retainability. QTL regions related to texture at harvest, postharvest, and for the storage index were identified on chromosomes 3, 12, and 16. Specifically, the SNPs located on chromosome 12 were shown to be potential novel markers for selection of crispness retention during storage, a valuable storability trait. These newly detected QTLs and underlying SNPs will represent a potential set of markers for the selection of the most favorable accessions characterized by superior fruit texture properties in ongoing breeding programs. Full article

Vitamin C (ascorbate; Asc) is a biologically important antioxidant that scavenges reactive oxygen species such as deleterious alkylperoxyl radicals (ROO^•), which are generated by radical-mediated oxidation of biomolecules in the presence of oxygen. The radical trapping proprieties of Asc are conventionally attributed to its ability to undergo single-electron transfers with reactive species. According to this mechanism, the reaction between Asc and ROO^• results in the formation of dehydroascorbate (DHA) and the corresponding hydroperoxides (ROOH). When studying the reactivity of DNA 5-(2′-deoxyuridinyl)methylperoxyl radicals, we discovered a novel pathway of ROO^• scavenging by Asc. The purpose of this study is to elucidate the underlying mechanism of this reaction with emphasis on the characterization of intermediate and final decomposition products. We show that the trapping of ROO^• by Asc leads to the formation of an alcohol (ROH) together with an unstable cyclic oxalyl-l-threonate intermediate (cOxa-Thr), which readily undergoes hydrolysis into a series of open-chain oxalyl-l-threonic acid regioisomers. The structure of products was determined by detailed MS and NMR analyses. The above transformation can be explained by initial peroxyl radical addition (PRA) onto the C2=C3 enediol portion of Asc. Following oxidation of the resulting adduct radical, the product subsequently undergoes Baeyer-Villiger rearrangement, which releases ROH and generates the ring expansion product cOxa-Thr. The present investigation provides robust clarifications of the peroxide-mediated oxidation chemistry of Asc and DHA that has largely been obscured in the past by interference with autooxidation reactions and difficulties in analyzing and characterizing oxidation products. Scavenging of ROO^• by PRA onto Asc may have beneficial consequences since it directly converts ROO^• into ROH, which prevents the formation of potentially deleterious ROOH, although it induces the breakdown of Asc into fragments of oxalyl-l-threonic acid. Full article

Retrotransposons are mobile DNA elements that are more active with increasing age and exacerbate aging phenotypes in multiple species. We previously reported an unexpected extension of chronological lifespan in the yeast, Saccharomyces paradoxus, due to the presence of Ty1 retrotransposons when cells were aged under conditions of mild stress. In this study, we tested a subset of genes identified by RNA-seq to be differentially expressed in S. paradoxus strains with a high-copy number of Ty1 retrotransposons compared with a strain with no retrotransposons and additional candidate genes for their contribution to lifespan extension when cells were exposed to a moderate dose of hydroxyurea (HU). Deletion of ADE8, NCS2, or TRM9 prevented lifespan extension, while deletion of CDD1, HAC1, or IRE1 partially prevented lifespan extension. Genes overexpressed in high-copy Ty1 strains did not typically have Ty1 insertions in their promoter regions. We found that silencing genomic copies of Ty1 prevented lifespan extension, while expression of Ty1 from a high-copy plasmid extended lifespan in medium with HU or synthetic medium. These results indicate that cells adapt to expression of retrotransposons by changing gene expression in a manner that can better prepare them to remain healthy under mild stress. Full article

The unscientific application of nitrogen (N) fertilizer not only increases the economic input of pear growers but also leads to environmental pollution. Improving plant N use efficiency (NUE) is the most effective economical method to solve the above problems. The absorption and utilization of N by plants is a complicated process. Glutamine synthetase (GS) and glutamate synthase (GOGAT) are crucial for synthesizing glutamate from ammonium in plants. However, their gene family in pears has not been documented. This study identified 29 genes belonging to the GS and GOGAT family in the genomes of Pyrus betulaefolia (P.be, 10 genes), Pyrus pyrifolia (P.py, 9 genes), and Pyrus bretschneideri (P.br, 10 genes). These genes were classified into two GS subgroups (GS1 and GS2) and two GOGAT subgroups (Fd–GOGAT and NADH–GOGAT). The similar exon–intron structures and conserved motifs within each cluster suggest the evolutionary conservation of these genes. Meanwhile, segmental duplication has driven the expansion and evolution of the GS and GOGAT gene families in pear. The tissue–specific expression dynamics of PbeGS and PbeGOGAT genes suggest significant roles in pear growth and development. Cis–acting elements of the GS and GOGAT gene promoters are crucial for plant development, hormonal responses, and stress reactions. Furthermore, qRT–PCR analysis indicated that PbeGSs and PbeGOGATs showed differential expression under exogenous hormones (GA₃, IAA, SA, ABA) and abiotic stress (NO₃⁻ and salt stress). In which, the expression of PbeGS2.2 was up–regulated under hormone treatment and down–regulated under salt stress. Furthermore, physiological experiments demonstrated that GA₃ and IAA promoted GS, Fd–GOGAT, and NADH–GOGAT enzyme activities, as well as the N content. Correlation analysis revealed a significant positive relationship between PbeGS1.1, PbeGS2.2, PbeNADH–GOGATs, and the N content. Therefore, PbeGS1.1, PbeGS2.2, and PbeNADH–GOGATs could be key candidate genes for improving NUE under plant hormone and abiotic stress response. To the best of our knowledge, our study provides valuable biological information about the GS and GOGAT family in the pear for the first time and establishes a foundation for molecular breeding aimed at developing high NUE pear rootstocks. Full article