Search Results (1,698)

Biological invasions threaten tropical biodiversity, yet the molecular mechanisms underlying successful invaders remain poorly understood. Thunbergia alata (Black-eyed Susan) is an aggressive “genomic orphan” invader in Andean forests, causing significant ecological disruption. This study contributes as one of the few transcriptomic profiles of light vs. shade responses in T. alata, providing a foundational molecular resource for this species. We performed differential expression analysis under varying light conditions, revealing a massive transcriptomic shift involving over 4000 differentially expressed genes. Our findings suggest a robust and stable homeostatic adaptation mechanism, characterized by the up-regulation of SnRK1 subunits for energy sensing and strategic management of Reactive Oxygen Species (ROS) within the thylakoid membrane. Furthermore, the fine-tuning of PIF/Auxin modules and the condition-specific induction of NAC and WRKY transcription factors facilitate shade avoidance and rapid vertical growth. The identification of a substantial reservoir of species-specific “not classified” genes suggests that novel genetic elements contribute to T. alata’s adaptive success. By elucidating these key regulatory networks, this research provides an important genomic baseline for future studies on adaptive evolution and the development of molecularly informed strategies for managing and controlling this invasive species in new environments. Full article

Background/Objectives: Autism spectrum disorder (ASD) can present with either an essential or a complex phenotype. The aim of this study was to compare clinical characteristics and the diagnostic yield of copy number variations (CNVs) in essential and complex phenotypes, and to evaluate risk factors. Methods: A total of 163 Turkish children (126 boys, 37 girls) who met the DSM-5 diagnostic criteria for ASD were evaluated. Chromosomal microarray analysis was performed. Results: Among the patients, 21.5% had a complex phenotype and 78.5% had an essential phenotype. Overall, 13.7% of the patients had a developmental/intelligence quotient (DQ/IQ) below 50, most of whom had a complex phenotype. In contrast, 15.3% of the patients had a DQ/IQ of 70 or higher, all of whom had an essential phenotype. The frequency of verbal individuals was 30.5% and did not differ between the two phenotypes. Pathogenic CNVs were identified in 7.4%; 17.1% of the complex group and 4.7% of the essential group. CNVs of uncertain significance that were potentially causal because they included an ASD-associated gene were present in 12.3% of individuals. CNV positivity was significantly higher in individuals with an IQ below 50; interestingly, it was similar between the verbal and non-verbal groups. Besides ultra-rare CNVs, recurrent CNVs associated with ASD were identified. A novel pathogenic CNV was identified at 2q13.33, including NPHP1 and BUB1, both of which are expressed in the brain and are potentially associated with ASD. Advanced parental age and preterm birth were identified as possible risk factors. Conclusions: Deep phenotyping is important for the management of both essential and complex phenotypes and allows the identification of patients with a higher probability of having CNVs. Reporting novel or rare CNVs contributes to clarifying the pathogenesis of ASD. Full article

RNA-binding proteins (RBPs) are essential regulators of RNA metabolism and gene expression, influencing processes such as splicing, stability, localization, and translation. Despite their critical roles in health and disease, including cancer, identifying RNA–protein interactions remains challenging due to technical limitations and biases of existing methods. Here we review and compare experimental techniques—including in vitro affinity purification, in vivo crosslinking, and proximity labeling—and computational prediction tools for RBP identification. We assess their strengths, limitations, and applicability across biological contexts, emphasizing the benefits of integrating experimental and computational strategies. Our analysis provides practical guidelines for selecting appropriate methodologies tailored to different cell types and research goals. These insights aim to facilitate more accurate mapping of RNA–protein interactomes, thereby advancing understanding of RBP functions and supporting the development of novel therapeutic interventions targeting RNA–protein complexes. Full article

Brucella spp. is a bacterium that can survive under conditions of nutrient starvation and is responsible for foodborne illnesses. The OmpR-type transcriptional regulator is characterized by an N-terminal receiver domain and a C-terminal domain, and it plays a regulatory role in diverse physiological processes, notably nitrogen and carbon metabolism. The genome of Brucella melitensis 16M contains genes for multiple OmpR-family regulators. However, the genetic program associated with nitrogen metabolism remains elusive. Herein, it was demonstrated that the B. melitensis 16M ΔftcR mutant, which lacks the OmpR-type regulator FtcR, displayed compromised viability upon recovery in a nitrogen- and carbon-free medium. Chromatin immunoprecipitation and next-generation sequencing were used to characterize the DNA-binding sites of FtcR. Our genome-wide analysis revealed extensive FtcR-binding sites throughout the B. melitensis 16M genome, including the identification of glnB as a novel target. As glnB encodes a P-II nitrogen regulator, this suggests FtcR plays a direct role in modulating nitrogen, carbon, and energy metabolism under prolonged nutrient starvation. In summary, our findings not only advance our understanding of the transcriptional regulation of nitrogen metabolism but also highlight its critical role in brucellosis pathogenesis, thereby paving the way for the development of novel therapeutics. Full article

Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), which are clonal hematopoietic disorders caused by somatic gene mutations in the JAK2, CALR, or MPL genes. Mutations activate the JAK–STAT pathway and disrupt NF-κB signaling, leading to a chronic inflammatory state caused by pro-inflammatory cytokines and reactive oxygen species (ROS). This altered microenvironment causes serious clinical features of the disease, such as bone marrow fibrosis, splenomegaly, vascular niche remodeling, and a greater probability of thrombosis or secondary leukemic transformation. Concurrently, MPNs cause both severe immune dysregulation and tumor evasion, as evidenced by progressive lymphopenia, T and B cell exhaustion, Natural Killer cell maturation arrest, and the accumulation of myeloid-derived suppressor cells. Although FDA-approved JAK1/JAK2 inhibitors ruxolitinib, fedratinib pacritinib and momelotinib effectively reduce splenomegaly and symptom burden and have demonstrated survival benefits in clinical trials, their ability to eliminate malignant clones or induce durable disease modification remains limited, and disease progression continues to occur in most patients. Finally, this review assesses the complex immunological dysfunction and chronic inflammatory dysregulation that characterize Ph-negative MPNs, as well as emerging therapeutic strategies, emphasizing the importance of fully understanding these intricate microenvironmental mechanisms for the identification and development of novel precision treatment targets. Full article

Cancer, the second leading cause of death worldwide, is a significant global challenge, and widespread, accessible, and early diagnostics are recognized as the most cost-effective strategies for reducing cancer burdens. Point-of-care (POC) systems offer an attractive alternative by enabling rapid and cost-effective diagnoses. We introduce a novel POC strategy for cancer biomarker identification based on monitoring the isothermal amplification of relevant cancer markers using a portable Arduino-based loop-mediated isothermal amplification (LAMP) system. The trajectory of the LAMP reaction during the first 3 min of the reaction is used as an indicator of the rate of amplification (defined as the m_P3 value). We obtained sets of m_P3 values that showed statistically significant differences in the genetic expression of four genes (ESR 1, PGR, Her2, and Ki67) within and between tissue spheroids derived from the MCF7, MDA-MB-231, Du145, and BJ fibroblast cell lines. We then used principal component analysis and clustering techniques to demonstrate that the m_P3 value sets derived from the expression of the four selected genes are sufficient to distinguish tissue spheroids derived from four different commercial cell lines. Further qPCR and immunostaining assays confirmed the quantitative LAMP (qLAMP) experimental trends. The immunostaining results were consistent with previous literature reports and with our qLAMP and qPCR results. We present a proof-of-concept demonstration of the use of a LAMP-based POC platform for the identification or discrimination of cancer tissues. Our strategy can be extended to other diseases associated with altered gene expression in body tissues or fluids. Full article

Sugarcane (Saccharum spp.) is a globally vital high-biomass sugar crop with a massive demand for potassium (K). Low-K⁺ stress severely restricts its yield and stress resistance. Plasma membrane intrinsic proteins (PIPs) play pivotal roles in transmembrane water transport and ion homeostasis; however, their evolutionary characteristics and molecular mechanisms underlying nutritional stress responses in the complex polyploid sugarcane remain poorly understood. In this study, genome-wide identification in the sugarcane cultivar XTT22 yielded 149 PIP gene family members (comprising 54 PIP1s and 95 PIP2s). Phylogenetic and chromosomal localization analyses demonstrated that the sugarcane PIP family underwent drastic paralogous expansion during evolution, with tandem duplication acting as the core driving force for the dramatic expansion of the PIP2 subfamily. Spatiotemporal expression profiling unveiled significant modular functional division among PIP genes, identifying a core co-expression group driving rapid early seedling elongation and a PIP2-specific expression cluster dedicated to the physiological homeostasis of mature stems. Notably, the core member ScPIP2-70 exhibited significant early-induced responses at both transcriptional and protein levels in roots under low-K⁺ stress. Functional complementation assays in the K⁺-uptake deficient yeast strain R5421 further confirmed that the heterologous expression of ScPIP2-70 effectively rescued the growth defects of yeast under low-K⁺ conditions, demonstrating its potential transmembrane K⁺ transport activity. This study not only comprehensively elucidates the evolutionary dynamics and spatiotemporal expression profiles of the sugarcane PIP gene family but also uncovers the novel pleiotropic function of ScPIP2-70 in mediating low-K⁺ stress tolerance, providing critical theoretical support and candidate gene resources for breeding “potassium-efficient” sugarcane cultivars via modern biotechnology. Full article

Background/Objectives: The identification of novel therapeutic targets is imperative to overcome the limitations of current anti-toxoplasmosis treatments. This study aims to investigate the potential of repurposing Pentamidine as an inhibitor against the HMG-Box domain-containing protein (TGARI_247020) in Toxoplasma gondii, a protein hypothesized to be essential for the parasite’s genomic stability. Methods: The study utilized a multi-layered in silico approach. First, the biological essentiality of the target gene was validated by analyzing CRISPR-Cas9-based phenomics data from the ToxoDB database. Second, the structural properties of the HMG-Box domain (ID: A0A139YAG1) were characterized using AlphaFold models. Finally, molecular docking simulations were conducted via the SwissDock server to evaluate the binding affinity and interaction dynamics between Pentamidine and the target protein. Results: Genomic analysis revealed a phenotype score of −1.2, confirming the indispensable role of the TGARI_247020 gene for parasite viability. Structural analysis identified a well-defined binding pocket within the HMG-Box domain. Molecular docking results demonstrated a high binding affinity for Pentamidine, yielding an optimal AC Score of −44.93, supported by a FullFitness value of −1134.13 kcal/mol. The interaction was primarily stabilized by a network of hydrogen bonds and favorable steric fits within the catalytic groove of the protein. Toxoplasmosis is widely classified as a neglected parasitic disease, posing persistent public health challenges and veterinary economic concerns globally. Traditional de novo drug discovery is often hindered by high costs and prolonged timelines, making drug repositioning (repurposing) a highly attractive and cost-effective strategy to identify novel therapeutics from established clinical agents over the past decade. Computer-Aided Drug Design (CADD), particularly Structure-Based Drug Design (SBDD), has provided a robust molecular framework to prioritize candidate drugs against essential parasitic targets. In apicomplexan parasites, high-mobility group box (HMGB) proteins, such as TgHMGB1a, serve as critical nuclear architectural factors that bind to distorted DNA structures and modulate genomic transcription, disrupting these essential DNA–protein interactions, representing a promising, yet under-explored, therapeutic target. The hypothesis for evaluating Pentamidine—an aromatic dicationic diamidine traditionally used in African trypanosomiasis—lies in its established ability to interact with nucleic acids and block critical molecular targets in other protozoa, providing a logical biochemical rationale for testing its potential as a structural inhibitor of the T. gondii HMG-box protein. Conclusions: Our findings provide preliminary in silico evidence that Pentamidine targets the HMG-Box protein, suggesting its potential for drug repurposing. However, due to established clinical limitations of Pentamidine (such as nephrotoxicity and poor blood–brain barrier permeability), further experimental in vitro and in vivo validation is strictly required to evaluate its therapeutic efficacy. Full article

Lipid phosphate phosphatases (LPPs) are critical regulatory factors in plant membrane lipid metabolism and lipid signal transduction, exerting key roles in membrane lipid remodeling, signal attenuation, and adaptation to abiotic stresses. However, the systematic identification of the soybean GmLPP gene family and its expression profiles in response to abiotic stresses remains largely unclear. In this study, a total of nine GmLPP family members were identified in the soybean genome, which were further classified into three subgroups based on their phylogenetic relationships. qRT-PCR analysis demonstrated that the majority of GmLPP genes responded to NaCl, PEG6000, NaHCO₃, JA, and SA treatments to varying extents, among which GmLPP7 exhibited the most pronounced response to salt stress. Subcellular localization assays demonstrated that the GmLPP7 protein is primarily localized to the cell membrane. Further haplotype analysis was performed on 160 soybean germplasm accessions, leading to the identification of five SNP loci within the GmLPP7 gene region. Among these, two SNPs were significantly associated with the relative germination index (STGI) and formed two distinct haplotypes. Notably, Hap2 exhibited a significantly higher STGI value, thus representing a superior salt-tolerant haplotype. In summary, this study systematically elucidates the evolutionary and expression profiles of the GmLPP gene family, identifies GmLPP7 as a candidate gene significantly associated with salt tolerance during soybean germination, and its superior haplotype Hap2, thereby providing novel genetic resources for the molecular improvement of salt tolerance in soybean. Full article

Background/Objectives: Hearing loss is one of the most prevalent sensory disorders in humans, with genetic factors accounting for approximately 60% of cases. Cochlear implantation is an effective intervention for individuals with severe-to-profound hearing loss. However, substantial variability in postoperative auditory performance persists, complicating the prediction of individual outcomes. This study investigated the genetic findings associated with hearing loss in a cohort of seven affected adults with cochlear implants (CIs). Methods: A total of seven patients with severe-to-profound hearing loss underwent genetic testing. Two of them were part of diagnostic screening, and five of them were part of research genetic analyses. Results: High-throughput genomic DNA sequencing identified twelve variants across multiple genes, including four new sequence variants. Based on ACMG/AMP criteria, integrating computational predictions, population frequency data, ClinVar annotations, and in silico pathogenicity assessments, the identified variants were classified as pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS). We detected one pathogenic variant, two likely pathogenic variants and nine variants of uncertain significance (VUS). Novel variants were further analyzed using multiple sequence alignment to assess evolutionary conservation. Conclusions: The identification of four novel variants within the analyzed patients underscores the genetic heterogeneity of hearing loss and the importance of genetic analyses for improving the understanding of its molecular basis. Further functional and clinical studies are required to determine the pathogenicity of these variants and their potential clinical relevance. Full article

Rising temperatures pose daunting challenges for sustainable yield and nutritional quality of rice (Oryza sativa L.), thus putting food security at risk. Limited information exists regarding cis-acting regulatory elements and candidate genes controlling the heat shock transcription factor (HSF) gene family in rice. Therefore, the present study identified HSF genes in the japonica (Nipponbare) and indica (9311) rice cultivars through in silico repositories. Three candidate genes (HSFC2B, HSFB1, and HSFC2A) were selected for qRT-PCR analysis to validate their expression patterns under heat stress (HS). The present findings reported a total of 25 OsHSF genes through in silico genome-wide identification. Comparative analysis illustrated that the OsHSF genes had structural similarities but different expression and transcriptional regulation between the two cultivars. HSF genes were unevenly distributed across the 12 rice chromosomes, suggesting that tandem duplication and gene repetition may have contributed to the evolution of novel genes. Phylogenetic analysis revealed that all OsHSF gene family members have shared common ancestry, but several genes lack introns, potentially facilitating swift stress responses as indicated by gene structure analysis. Expression analysis revealed that candidate genes were active, with HSFC2A exhibiting the highest level of expression in the japonica cultivar compared to indica under heat-stressed conditions. HSFC2B gene showed a higher statistical difference in its response between cultivars, time points, and cultivar vs. time points interactions compared to HSFC2A and HSFB1. These findings offer valuable insights into the function of OsHSF genes that will contribute to the development of climate-resilient rice cultivars. Full article

The SWEET (Sugars Will Eventually be Exported Transporter) family, a class of sugar transporters identified in recent years, plays important roles in plant growth and development. Increasing evidence suggests that SWEET genes are also involved in plant responses to abiotic stresses, including salt stress. However, the genome-wide composition and salt-responsive functions of SWEET genes in Elymus nutans Griseb. have not been systematically characterized to date. This study presents the first genome-wide identification of the SWEET gene family in E. nutans and functional characterization of EnSWEET15 in salt stress response, providing candidate genes and a theoretical basis for improving salt tolerance in this species. A total of 12 EnSWEET genes were identified from the E. nutans genome and were unevenly distributed across eight chromosomes. Phylogenetic analysis classified them into four subfamilies, and promoter analysis revealed abundant cis-elements related to hormone signaling and stress responses, suggesting roles in abiotic stress adaptation. Expression analysis showed that EnSWEET15 was significantly upregulated in both roots and leaves under salt stress. The full-length EnSWEET15 coding sequence (930 bp ORF) was cloned and functionally characterized. Heterologous overexpression in Arabidopsis thaliana indicated that EnSWEET15 enhances salt tolerance. Transgenic lines showed reduced reactive oxygen species (ROS) accumulation and increased activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), compared with wild-type plants under salt stress. Overall, this study identifies EnSWEET15 as a positive regulator of salt tolerance via modulating ROS homeostasis, providing novel insights into SWEET-mediated salt stress response in perennial forages and valuable genetic resources for salt-tolerant breeding of E. nutans. Full article

Background: Epigenomics has emerged as an essential field in modern molecular biology, providing a critical layer of gene regulation. DNA methylation, histone modifications and alterations to the chromatin accessibility of DNA have been widely associated with complex diseases including cancer. The most recent developments in high-throughput sequencing technology have made it possible to profile epigenetic landscapes genomically on a large scale. However, bulk averaging can obscure cellular heterogeneity essential for understanding complex disease states. The purpose of the review is to survey accessible tools and algorithms to conduct an Epigenomic study in the field of biomedical research, from bulk tissue analysis to the high-resolution frontier of single-cell epigenomics. Methods: We performed a comparative analysis of common methods used to analyze DNA methylation, chromatin immunoprecipitation, sequencing analysis and chromatin accessibility profiling. We described the standardized bioinformatics tools and pipelines required to transform raw sequencing data into mechanistic biological understanding, highlighting the role of quality control, peak calling, and differential analysis. Furthermore, we explore the integration of epigenomics with other “omics” layers through advanced computational frameworks, including machine learning and network-based modeling. Results: These advanced multi-omics techniques demonstrate promising clinical utility by enabling biomarker discovery, disease subtyping, and identification of novel therapeutic targets. Conclusions: Despite challenges with data complexity, the fusion of Artificial Intelligence (AI) and single-cell technologies will accelerate the transition toward precision medicine. Full article

In this study, we report for the first time the cloning and identification of three melatonin receptors (PgMtnr1a, PgMtnr1b, and PgMtnr1c) from the freeze-resistant fish Perccottus glenii, all of which encode typical GPCR proteins. These receptors are expressed widely in high-metabolism tissues such as the liver. During the freezing and recovery process at −2 °C, the expression of liver receptors exhibited dynamic changes: PgMtnr1a and PgMtnr1c were significantly upregulated during the middle of resuscitation, while PgMTNR1A reached its peak expression in the later stages, suggesting its involvement in stress repair. In vitro experiments confirmed that melatonin significantly enhances the activity of liver antioxidant enzymes in a receptor-dependent manner, an effect that can be inhibited by the antagonist luzindole. Anti-inflammatory analyses indicate that melatonin primarily inhibits inflammation-related genes through Mtnr1a and Mtnr1b. Furthermore, the overexpression of PgMTNR1A can synergistically activate ERK in the presence of melatonin, inhibit the JNK/p38 MAPK pathway, and downregulate the expression of NF-κB and COX2. Pathway inhibition experiments further validated that the MAPK/NF-κB axis, including ERK, JNK, and p38 pathways, mediates the anti-inflammatory effects of melatonin. This study systematically elucidates the molecular mechanisms by which the melatonin receptors of P. glenii play crucial antioxidant and anti-inflammatory roles during the later stages of freeze–thaw resuscitation, particularly by regulating the MAPK/NF-κB signaling axis through MTNR1A, thereby providing a novel basis for understanding the adaptation of vertebrates to extreme environments. Full article

Saline–alkali stress is a widespread abiotic stress that severely impairs crop growth and yield formation. Iron Chlorin e6 (ICe6), a novel plant growth regulator, is essentially a chlorophyll derivative, and possesses potential application value in regulating plant chlorophyll metabolism and improving plant stress resistance. In this study, the saline–alkali-sensitive soybean cultivar Henong 95 and saline–alkali-tolerant soybean cultivar Hefeng 50 were used as experimental materials, and foliar spraying with 120 nmol/L ICe6 was conducted at the R1 stage. The results indicated that relative to CK, SA treatment markedly inhibited soybean growth, accompanied by reduced antioxidant capacity, excessive reactive oxygen species (ROS) accumulation and significantly lowered photosynthetic pigment content. Carbohydrate accumulation was substantially suppressed, which ultimately resulted in yield reduction (HN95: −12.31%; HF50: −11.08%). ICe6 treatment mitigated saline–alkali-induced growth inhibition in soybean plants, as reflected by markedly restored antioxidant indices, sharply decreased malondialdehyde (MDA), H₂O₂, and O₂⁻ levels, and notably increased leaf area (HN95: +49.72%; HF50: +19.82%) and chlorophyll content (HN95: +36.06%; HF50: +90.75%). Combined transcriptomic and metabolomic profiling showed that, relative to the SA control, ICe6 treatment led to the identification of 2896 DEGs in HN95 and 3530 DEGs in HF50, with significant enrichment in photosynthesis- and chlorophyll metabolism-related pathways, e.g., GO:0009765 (photosynthesis, light harvesting). Differential metabolites were chiefly enriched in isoflavonoid biosynthesis—a source of antioxidants—and amino acid biosynthesis, which governs chlorophyll precursor synthesis. These findings suggest that ICe6 may enhance chlorophyll content by modulating the expression of genes involved in chlorophyll metabolism, contributing to light capture and chlorophyll biosynthesis, facilitating carbohydrate accumulation and ultimately contributing to increased yield under saline–alkali stress (HN95: +5.74%; HF50: +5.83%). Full article