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Results for “comparative transcriptomics”

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PubMed2007

Serial analysis of gene expression in sugarcane (Saccharum spp.) leaves revealed alternative C4 metabolism and putative antisense transcripts.

Sugarcane (Saccharum spp.) is a highly efficient biomass and sugar producing crop. Leaf reactions have been considered as potential rate-limiting step for sucrose accumulation in sugarcane stalks. To characterize the sugarcane leaf transcriptome, field-grown mature leaves from cultivar "SP80-3280" were analyzed using Serial Analysis of Gene Expression (SAGE). From 480 sequenced clones, 9,482 valid tags were extracted, with 5,227 unique sequences, from which 3,659 (70%) matched at least a sugarcane assembled sequence (SAS) with putative function; while 872 tags (16.7%) matched SAS with unknown function; 523 (10%) matched SAS without a putative annotation; and only 173 (3.3%) did not match any sugarcane ESTs. Based on gene ontology (GO), photosystem (PS) I reaction center was identified as the most frequent gene product location, followed by the remaining sites of PS I, PS II and thylakoid complexes. For metabolic processes, photosynthesis light harvesting complexes; carbon fixation; and chlorophyll biosynthesis were the most enriched GO-terms. Considering the alternative photosynthetic C(4) cycles, tag frequencies related to phosphoenolpyruvate carboxykinase (PEPCK) and aspartate aminotransferase compared to those for NADP(+)-malic enzyme (NADP-ME) and NADP-malate dehydrogenase, suggested that PEPCK-type decarboxylation appeared to predominate over NADP-ME in mature leaves, although both may occur, opposite to currently assumed in sugarcane. From the unique tag set, 894 tags (17.1%) were assigned as potentially derived from antisense transcripts, while 73 tags (1.4%) were assigned to more than one SAS, suggesting the occurrence of alternative processing. The occurrence of antisense was validated by quantitative reverse transcription amplification. Sugarcane leaf transcriptome provided new insights for functional studies associated with sucrose synthesis and accumulation.

Carbohydrate Metabolism↗

PubMed2003

Transcriptomic classification of antitumor agents: application to the analysis of the antitumoral effect of SR31747A.

SR31747A is a sigma ligand that exhibits a potent antitumoral activity on various human tumor cell lines both in vitro and in vivo. To understand its mode of action, we used DNA microarray technology combined with a new bioinformatic approach to identify genes that are modulated by SR31747A in different human breast or prostate cancer cell lines. The SR31747A transcriptional signature was also compared with that of seven different representative anticancer drugs commonly used in the clinic. To this aim, we performed a two-dimensional hierarchical clustering analysis of drugs and genes which showed that 1) standard molecules with similar mechanism of action clustered together and 2) SR31747A does not belong to any previously characterized class of standard anticancer drugs. Moreover, we showed that 3) SR31747A mainly exerted its antiproliferative effect by inhibiting the expression of genes playing a key role in DNA replication and cell cycle progression. Finally, contrasting with other drugs, we obtained evidence that 4) SR31747A strongly inhibited the expression of three key enzymes of the nucleotide synthesis pathway (i.e., dihydrofolate reductase, thymidylate synthase, and thymidine kinase) with the latter shown both at the mRNA and protein levels. These results, obtained through a novel molecular approach to characterize and compare anticancer agents, showed that SR31747A exhibits an original mechanism of action, very likely through unexpected targets whose modulations may account for its antitumoral effect.

Antineoplastic Agents↗

PubMed2025

Decoding nitrogen uptake efficiency in maize and sorghum: insights from comparative gene regulatory networks.

Nitrogen (N) is an essential macronutrient for plant growth and yield, yet optimizing nitrogen use efficiency remains a challenge in agriculture. To better understand the regulatory basis of plant responses to N availability, we constructed a maize-specific nitrogen uptake efficiency gene regulatory network (mNUEGRN) comprising 1625 protein-DNA interactions (PDI) between 70 promoters and 301 transcription factors using enhanced yeast one-hybrid assays. We also projected a sorghum NUE GRN (spNUEGRN) based on maize orthologs and analyzed N-responsive subnetworks in both species using transcriptome profiling under N stress of early deprivation and recovery. Cross-species comparison with an existing Arabidopsis GRN revealed about 18% conserved interaction, corresponding to 11% of the mNUEGRN, particularly within the nitrate assimilation pathways. Notably, bZIP18 and bZIP30 emerged as central regulators in mNUEGRN, forming highly connected feed-forward loops (FFLs). From our time series data, we identified 19 236 and 23 864 differentially expressed genes in maize and sorghum, respectively. Gini correlation analysis uncovered 764 and 638 FFLs in mNUEGRN and spNUEGRN, respectively, of which 22 FFLs in maize and 35 in sorghum were identified in both leaf and root for each species. These FFLs may represent candidate regulatory motifs that contribute to modulating transcriptional responses under fluctuating N conditions, but their potential roles require further investigation. Together, our findings reveal evolutionarily conserved and species-specific regulatory strategies that mediate early N responsiveness, offering a foundation for engineering crops with improved NUE.

Sorghum↗

PubMed2024

Deciphering the ghost proteome in ovarian cancer cells by deep proteogenomic characterization.

Proteogenomics is becoming a powerful tool in personalized medicine by linking genomics, transcriptomics and mass spectrometry (MS)-based proteomics. Due to increasing evidence of alternative open reading frame-encoded proteins (AltProts), proteogenomics has a high potential to unravel the characteristics, variants, expression levels of the alternative proteome, in addition to already annotated proteins (RefProts). To obtain a broader view of the proteome of ovarian cancer cells compared to ovarian epithelial cells, cell-specific total RNA-sequencing profiles and customized protein databases were generated. In total, 128 RefProts and 30 AltProts were identified exclusively in SKOV-3 and PEO-4 cells. Among them, an AltProt variant of IP_715944, translated from DHX8, was found mutated (p.Leu44Pro). We show high variation in protein expression levels of RefProts and AltProts in different subcellular compartments. The presence of 117 RefProt and two AltProt variants was described, along with their possible implications in the different physiological/pathological characteristics. To identify the possible involvement of AltProts in cellular processes, cross-linking-MS (XL-MS) was performed in each cell line to identify AltProt-RefProt interactions. This approach revealed an interaction between POLD3 and the AltProt IP_183088, which after molecular docking, was placed between POLD3-POLD2 binding sites, highlighting its possibility of the involvement in DNA replication and repair.

Humans↗

PubMed2024

Adaptation for Staphylococcus aureus to hosts via insertion mutation in the accessory gene regulator agrC gene: decreased virulence and enhanced persistence capacity.

UNLABELLED: Staphylococcus aureus is an important human pathogen due to its vast array of virulence factors regulated by multiple regulatory mechanisms, including the accessory gene regulator. In this study, two S. aureus strains were simultaneously isolated from the blood of a febrile patient, belonging to the same clone, designated as 23H with a complete hemolytic phenotype, and 23B, exhibiting an incomplete hemolytic phenotype. The genomic comparison between strains 23B and 23H revealed that 23B had a single adenine base insertion at position 923 in the agrC gene, leading to a functional loss of the encoded AgrC. Experimental findings showed that strain 23B had decreased hemolytic activity, lower cytotoxicity against human alveolar epithelial A549 cells and in the Galleria mellonella model, and a reduced ability to survive intracellularly after infecting macrophages, in comparison to 23H. Conversely, 23B exhibited enhanced biofilm formation, greater adherence to A549 cells, and increased persistence in the face of vancomycin and daptomycin treatment. Transcriptomic analysis revealed that 23B upregulated surface protein-encoding genes while simultaneously reducing the expression levels of virulence factors, highlighting the intricate regulatory adjustments facilitating its persistence and reducing pathogenic potential. ATP assay results indicated that 23B maintained elevated ATP levels during the exponential phase yet exhibited reduced levels in the stationary phase when compared with 23H. Our findings suggested that the mutation in the agrC gene of S. aureus results in diminished virulence but markedly enhances persistence. This mutated strain warrants clinical attention because it may lead to treatment failures and persist in patients. IMPORTANCE: In clinical antimicrobial therapy, bacterial strains often develop resistance to antimicrobial agents. Additionally, mutations in their gene regulatory networks can increase their persistence, especially in immunocompromised patients. This study identified an insertion mutation in the accessory gene regulator, agrC gene, carried by a Staphylococcus aureus strain isolated from the blood of a febrile patient, leading to the functional loss of AgrC. Further research revealed that despite the reduced virulence of the mutated strain, it significantly bolstered the capacity to adapt and endure within the host during prolonged infections. This was evidenced by increased adhesion and biofilm formation capabilities, development of antimicrobial tolerance, and decreased ATP levels linked to persistence. Therefore, monitoring these mutations in S. aureus is crucial clinically, as they can complicate treatment strategies.

Staphylococcus aureus↗

PubMed2004

A comparison of differences in the gene expression profiles of phorbol 12-myristate 13-acetate differentiated THP-1 cells and human monocyte-derived macrophage.

In order to characterize the monocytic cell line THP-1 and its mature, macrophage-like form treated with phorbol 12-myristate 13-acetate (PMA), we have conducted an oligonucleotide microarray assay and compared the results with those from an assay of human monocytes and macrophages. We found that early THP-1 cells have a pattern of gene expression distinct from monocytes, and when treated with PMA, certain genes which are induced in macrophages, such as apolipoprotein-E, matrix metalloproteinase 9 and alpha2 macroglobulin are also induced in the PMA-treated THP-1 cells (THP1PMA cells). However, these were some genes which are conversely regulated among macrophages and THP1PMA cells such as interleukin-1-beta and the overall correlation coefficient was not very high. It is shown that, although certain morphological and other characteristics of PMA-differentiated THP-1 cells are similar to macrophages, from a transcriptomic view, the two are different. This suggests a need for careful recognition of and allowance for this difference when interpreting the results of experiments done with THP-1 cells in which it is otherwise assumed they are representative of the macrophage.

Blotting, Northern↗

PubMed2006

Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis.

Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling approach, we found approximately 17% of all B. pseudomallei genes displaying regulated expression during growth in rich medium, occurring as broad waves of functionally coherent gene expression tightly associated with distinct growth phases and transition points. We observed regulation of virulence genes across all growth phases and identified serC as a potentially new virulence factor by virtue of its coexpression with other early-phase virulence genes. serC-disrupted B. pseudomallei strains were serine auxotrophs and in mouse infection assays exhibited a dramatic attenuation of virulence compared to wild-type B. pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also conferred protection against subsequent challenges with different wild-type B. pseudomallei strains. At a genomic level, early-phase genes were preferentially localized on chromosome 1, while stationary-phase genes were significantly biased towards chromosome 2. We detected a significant level of chromosomally clustered gene expression, allowing us to predict approximately 100 potential operons in the B. pseudomallei genome. We computationally and experimentally validated these operons by showing that genes in these regions are preferentially transcribed in the same 5'-->3' direction, possess significantly shorter intergenic lengths than the overall genome, and are expressed as a common mRNA transcript. The availability of this transcriptome map provides an important resource for understanding the transcriptional architecture of B. pseudomallei.

Animals↗

PubMed2026

Cooccurrence of Homologous Recombination Deficiency and Mismatch Repair Deficiency in Colorectal Cancer.

Homologous recombination deficiency (HRD) in colorectal cancer (CRC) remains largely unexplored. In contrast, mismatch repair deficiency (dMMR) occurs in ∼15% of patients with CRC. Although HRD and dMMR have historically been regarded as mutually exclusive, emerging evidence suggests that this mutual exclusivity may not be absolute. Here, we conducted a retrospective cohort study utilizing genomic and transcriptomic data to define HRD status in a Chinese dMMR CRC cohort (n = 99). Multiple machine learning approaches were employed to analyze the expression profiles of these tumors and to develop a classifier distinguishing HRD from homologous recombination proficiency (HRP) in dMMR CRCs. In the Chinese dMMR CRC cohort, 66% of tumors were classified as HRD. Compared with the HRP group, the HRD group had a significantly higher tumor mutational burden and better outcomes. The derived expression signature, comprising eight genes, successfully predicted HRD status in dMMR tumors with high accuracy in the training set (AUC = 0.88, Naïve Bayes) and the test set (AUC = 0.87). In this study, a subset of dMMR CRC tumors with co-occurring HRD was identified, which may have potential implications for patient stratification and the application of targeted therapies, such as PARP inhibitors, in this molecular subgroup.

colorectal cancer↗

PubMed2004

From masking repeats to identifying functional repeats in the mouse transcriptome.

The back-to-back release of the mouse genome and the functionally annotated RIKEN mouse full-length cDNA collection was an important milestone in mammalian genomics. Yet much of the data remain to be explored in terms of biological effects and mechanisms. For example, interspersed repeats account for 39 per cent of the mouse genome sequence and 11 per cent of representative transcripts. A considerable number of transposable repeat elements are still active and propagating in mouse compared with human. While existing repeat databases and tools assist the classification of repeats or identification of new repeats, there is little bioinformatic support towards exploring the extent and role of repeats in transcriptional variation, modulation of protein function, or gene regulatory events. Since the mouse is used as a model organism to study human genes and their disease associations, this review focuses on information extraction and collation that captures the functional context of repeats in mouse transcripts to facilitate the biological interpretation and extrapolation of findings to the human.

Animals↗

PubMed2005

The potassium transporter AtHAK5 functions in K(+) deprivation-induced high-affinity K(+) uptake and AKT1 K(+) channel contribution to K(+) uptake kinetics in Arabidopsis roots.

Potassium is an important macronutrient and the most abundant cation in plants. Because soil mineral conditions can vary, plants must be able to adjust to different nutrient availabilities. Here, we used Affymetrix Genechip microarrays to identify genes responsive to potassium (K(+)) deprivation in roots of mature Arabidopsis (Arabidopsis thaliana) plants. Unexpectedly, only a few genes were changed in their expression level after 6, 48, and 96 h of K(+) starvation even though root K(+) content was reduced by approximately 60%. AtHAK5, a potassium transporter gene from the KUP/HAK/KT family, was most consistently and strongly up-regulated in its expression level across 48-h, 96-h, and 7-d K(+) deprivation experiments. AtHAK5 promoter-beta-glucuronidase and -green fluorescent protein fusions showed AtHAK5 promoter activity in the epidermis and vasculature of K(+) deprived roots. Rb(+) uptake kinetics in roots of athak5 T-DNA insertion mutants and wild-type plants demonstrated the absence of a major part of an inducible high-affinity Rb(+)/K(+) (K(m) approximately 15-24 microm) transport system in athak5 plants. In comparative analyses, uptake kinetics of the K(+) channel mutant akt1-1 showed that akt1-1 roots are mainly impaired in a major transport mechanism, with an apparent affinity of approximately 0.9 mm K(+)(Rb(+)). Data show adaptation of apparent K(+) affinities of Arabidopsis roots when individual K(+) transporter genes are disrupted. In addition, the limited transcriptome-wide response to K(+) starvation indicates that posttranscriptional mechanisms may play important roles in root adaptation to K(+) availability in Arabidopsis. The results demonstrate an in vivo function for AtHAK5 in the inducible high-affinity K(+) uptake system in Arabidopsis roots.

Arabidopsis↗

PubMed2006

Global transcriptional and physiological responses of Saccharomyces cerevisiae to ammonium, L-alanine, or L-glutamine limitation.

The yeast Saccharomyces cerevisiae encounters a range of nitrogen sources at various concentrations in its environment. The impact of these two parameters on transcription and metabolism was studied by growing S. cerevisiae in chemostat cultures with l-glutamine, l-alanine, or l-ammonium in limitation and by growing cells in an excess of ammonium. Cells grown in l-alanine-limited cultures had higher biomass yield per nitrogen mole (19%) than those from ammonium-limited cultures. Whole-genome transcript profiles were analyzed with a genome-scale metabolic model that suggested increased anabolic activity in l-alanine-limited cells. The changes in these cells were found to be focused around pyruvate, acetyl coenzyme A, glyoxylate, and alpha-ketoglutarate via increased levels of ALT1, DAL7, PYC1, GDH2, and ADH5 and decreased levels of GDH3, CIT2, and ACS1 transcripts. The transcript profiles were then clustered. Approximately 1,400 transcripts showed altered levels when amino acid-grown cells were compared to those from ammonium. Another 400 genes had low transcript levels when ammonium was in excess. Overrepresentation of the GATAAG element in their promoters suggests that nitrogen catabolite repression (NCR) may be responsible for this regulation. Ninety-one genes had transcript levels on both l-glutamine and ammonium that were decreased compared to those on l-alanine, independent of the concentration. The GATAAG element in these genes suggests two groups of NCR-responsive genes, those that respond to high levels of nitrogen and those that respond to levels below 30 muM. In conclusion, our results reveal that the nitrogen source has substantial influence on the transcriptome of yeasts and that transcriptional changes may be correlated to physiology via a metabolic model.

Alanine↗

PubMed2026

Transcriptome-based high-frequency recurrence index predicts frequent recurrence in non-muscle-invasive bladder cancer after Bacillus Calmette-Guérin therapy.

BACKGROUND: High-frequency recurrence (HfR, ≥ 2 recurrences) in non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical burden. Current risk models, such as the European Organization for Research and Treatment of Cancer (EORTC), the European Association of Urology (EAU), and the UROMOL classification, offer limited predictive accuracy for identifying patients at risk for frequent recurrence despite appropriate treatment. METHODS: A 75-gene high-frequency recurrence index (HfRI) was constructed by selecting recurrence-associated genes using differential expression and Cox regression analyses. The HfRI was computed as a weighted sum of normalized gene expression values. The model was trained on a discovery cohort and validated in multiple cohorts (n = 1379) using machine-learning approaches. Clinical relevance was assessed using recurrence-free survival (RFS) and Cox models, and predictive performance was compared with that of the EORTC, EAU, and UROMOL classifications using the area under the curve (AUC) and the concordance index (c-index). RESULTS: The HfRI robustly stratified patients into high-risk and low-risk groups across six independent NMIBC cohorts. Patients classified as HfRI-high had a significantly greater likelihood of experiencing ≥ 2 recurrences (χ2, p = 0.001) and showed markedly reduced RFS (log-rank test, p < 0.001). The adverse prognostic effect of the HfRI persisted even among patients treated with BCG therapy (log-rank test, p = 0.02). Multivariate analysis revealed that the HfRI was an independent predictor of HfR (HR = 2.82, 95% CI = 1.89-4.20, p < 0.001). Compared with established clinical risk classifiers, the HfRI demonstrated superior predictive performance (AUC = 0.736, c-index = 0.673) in terms of the EORTC (AUC = 0.594), EAU (AUC = 0.557) risk groups, and UROMOL2021 (AUC = 0.596) classification. Pathway analysis revealed that HfRI-high tumors were characterized by upregulation of cell cycle progression and DNA replication pathways, accompanied by suppression of immune signaling pathways. These biological features provide a mechanistic explanation for the reduced responsiveness to intravesical BCG therapy, underscoring the role of HfRI not only as a predictor of recurrence risk but also as a biomarker capable of identifying patients unlikely to benefit from standard BCG treatment. CONCLUSIONS: HfRI represents a robust, transcriptome-based tool for predicting frequent recurrence in NMIBC patients. The HfRI supports earlier identification of patients at risk of high-frequency recurrence, thereby supporting personalized treatment strategies.

Humans↗

PubMedDate not supplied

Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray.

OBJECTIVES: Aging is associated with significant alterations in gene expression in numerous organs and tissues. Anti-aging therapy with peptide bioregulators holds much promise for the correction of age-associated changes, making a screening for their molecular targets in tissues an important question of modern gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. In humans, Cortagen demonstrated a pronounced therapeutic effect upon the structural and functional posttraumatic recovery of peripheral nerve tissue. Importantly, other effects were also observed in cardiovascular and cerebrovascular parameters. DESIGN: Based on these latter observations, we hypothesized that acute course of Cortagen treatment, large-scale transcriptome analysis, and identification of transcripts with altered expression in heart would facilitate our understanding of the mechanisms responsible for this peptide biological effects. We therefore analyzed the expression of 15,247 transcripts in the heart of female 6-months CBA mice receiving injections of Cortagen for 5 consecutive days was studied by cDNA microarrays. RESULTS: Comparative analysis of cDNA microarray hybridisation with heart samples from control and experimental group revealed 234 clones (1,53% of the total number of clones) with significant changes of expression that matched 110 known genes belonging to various functional categories. Maximum up- and down-regulation was +5.42 and -2.86, respectively. CONCLUSION: Intercomparison of changes in cardiac expression profile induced by synthetic peptides (Cortagen, Vilon, Epitalon) and pineal peptide hormone melatonin revealed both common and specific effects of Cortagen upon gene expression in heart.

Animals↗

PubMed2026

ELISA (Embedding-Linked Interactive Single-cell Agent): an interpretable hybrid generative Artificial Intelligence agent for expression-grounded discovery in single-cell genomics.

Translating single-cell RNA sequencing (scRNA-seq) data into mechanistic biological hypotheses remains a critical bottleneck, as agentic AI systems lack direct access to transcriptomic representations while expression foundation models remain opaque to natural language. Here, we introduce ELISA (Embedding-Linked Interactive Single-cell Agent), an interpretable framework that unifies single-cell generative pretrained transformer expression embeddings with biomedical bidirectional encoder representations from transformers-based semantic retrieval and large-language model (LLM)-mediated interpretation for interactive single-cell discovery. An automatic query classifier routes inputs to gene marker scoring, semantic matching, or reciprocal rank fusion pipelines depending on whether the query is a gene signature, natural language concept, or mixture of both. Integrated analytical modules perform pathway activity scoring across 60+ gene sets, ligand-receptor interaction prediction using 280+ curated pairs, condition-aware comparative analysis, and cell-type proportion estimation, all operating directly on embedded data without access to the original count matrix. Benchmarked across six diverse scRNA-seq datasets spanning inflammatory lung disease, pediatric and adult cancers, organoid models, healthy tissue, and neurodevelopment, ELISA significantly outperforms CellWhisperer, a classical lexical retriever (BM25), and a random baseline in cell type retrieval (combined permutation test, $p < 2\times 10^{-5}$ for each), with particularly large gains on gene-signature queries (Cohen's $d = 5.98$ for mean reciprocal rank). ELISA replicates published biological findings (mean composite score 0.88), and generates candidate hypotheses through grounded LLM reasoning, bridging the gap between transcriptomic data exploration and biological discovery.

Generative Artificial Intelligence↗

PubMed2026

Comparative evaluation of chitosan-based and star polycation nanocarriers for enhanced RNAi efficacy targeting CmFibL in Cnaphalocrocis medinalis.

BACKGROUND: The rice leaf folder, Cnaphalocrocis medinalis, causes substantial rice yield losses through larval leaf-rolling behavior. RNA interference (RNAi) offers a sustainable alternative, but its application in Lepidoptera is hindered by dsRNA degradation and poor cellular uptake. This study developed nanocarrier-mediated dsRNA delivery to overcome these limitations. RESULTS: Three nanocarriers - chitosan (CS), chitosan-tripolyphosphate (CS-TPP), and star polycation (SPc) - were compared for enhancing RNAi efficiency targeting the C. medinalis fibroin light chain gene (CmFibL). CS-TPP and SPc achieved 61% and 55% silencing efficiency, respectively, representing 2.7-fold improvement over naked dsRNA (23%). All nanocarriers protected dsRNA from RNase A (30 min) and midgut fluid (6 h) degradation. CmFibL knockdown caused severe silk defects, prolonged pupal duration by 23%, reduced pupal weight by 33%, and decreased leaf-rolling damage by 31% in glasshouse cage trials. Transcriptomics revealed down-regulation of amino acid metabolism and activation of endoplasmic reticulum (ER) stress and immune responses. No off-target effects were detected in human genome, nor in any predators or parasitoids sharing the same ecological niche. CONCLUSION: CS-TPP and SPc nanocarriers effectively enhance RNAi efficiency in a Lepidopteran pest. Targeting CmFibL disrupts silk-mediated feeding shelters with minimal ecological risk, providing a practical framework for field application of RNAi-based biopesticides against leaf-rolling rice pests. © 2026 Society of Chemical Industry.

Animals↗

PubMed2006

Gene expression profiling of human endothelial cells exposed to 50-Hz magnetic fields fails to produce regulated candidate genes.

To address the question of a possible effect of magnetic fields (MF) at 50 Hz on living systems, gene expression analyses were performed on human primary vascular endothelial cells exposed to MF of various intensities compared to control cells. Exposure protocols included continuous exposure at a single intensity (10 and 700 microT), intermittent exposure at a single intensity (700 microT), and continuous exposure to a variable-intensity field (10-30 microT). The transcriptional response of the cells was investigated using oligonucleotide microarrays containing up to 30 000 unique features. Although in individual experiments genes were identified where the expression appeared to be affected by exposure to MF, none of these genes were regulated in the same manner in subsequent repetition experiments. This is the first report of a transcriptome-wide analysis of the effects of MF exposure on human cells. The lack of a reproducible effect of MF on the expression of any genes in our investigation adds further weight to the evidence that 50-Hz MF are not capable of interacting with biological systems and thus do not represent an endothelial stress factor.

Cell Culture Techniques↗

PubMed2006

The DtxR regulon of Corynebacterium glutamicum.

Previous studies with Corynebacterium diphtheriae and Mycobacterium species revealed that the transcriptional regulator DtxR and its ortholog IdeR play a central role in the control of iron metabolism. In the present work, we used genome-based approaches to determine the DtxR regulon of Corynebacterium glutamicum, a nonpathogenic relative of C. diphtheriae. First, global gene expression of a dtxR deletion mutant was compared with that of the wild type using DNA microarrays. Second, we used a computer-based approach to identify 117 putative DtxR binding sites in the C. glutamicum genome. In the third step, 74 of the corresponding genome regions were amplified by PCR, 51 of which were shifted by the DtxR protein. Finally, we analyzed which of the genes preceded by a functional DtxR binding site showed altered mRNA levels in the transcriptome comparison. Fifty-one genes organized in 27 putative operons displayed an increased mRNA level in the DeltadtxR mutant and thus are presumably repressed by DtxR. The majority of these genes are obviously involved in iron acquisition, three encode transcriptional regulators, e.g., the recently identified repressor of iron proteins RipA, and the others encode proteins of diverse or unknown functions. Thirteen genes showed a decreased mRNA level in the DeltadtxR mutant and thus might be activated by DtxR. This group included the suf operon, whose products are involved in the formation and repair of iron-sulfur clusters, and several genes for transcriptional regulators. Our results clearly establish DtxR as the master regulator of iron-dependent gene expression in C. glutamicum.

Bacterial Proteins↗

PubMed2024

Genetic association between epilepsy and gliomas: Insights from Mendelian randomization and single-cell transcriptomic analyses.

BACKGROUND: Seizures are prevalent in glioma patients, especially in those with low-grade gliomas. The interaction between gliomas and epilepsy involves complex biological mechanisms that are not fully understood. METHODS: We collected Genome-Wide Association Study data for epilepsy and gliomas, performed differential expression analysis, and conducted Gene Ontology (GO) enrichment analysis on the identified genes. Single-cell RNA sequencing data (scRNA-seq) from GSE221534 dataset in Gene Expression Omnibus (GEO) were used to analyze cell-cell interactions within glioma samples from patients with and without epilepsy. RESULTS: Mendelian Randomization (MR) analysis revealed significant associations between genetic variants related to epilepsy and glioma risk, suggesting a potential causal relationship, especially in astrocytomas. Differential expression analysis identified epilepsy-related genes that were significantly upregulated in astrocytoma tissues compared to normal brain tissues. GO enrichment analysis indicated that these genes are involved in critical biological processes such as neurogenesis and cellular signaling. The scRNA-seq analysis showed, compared to non-epileptic samples, glioma stem cells, microglia, and NK cells are increased in the core regions of astrocytomas in epileptic patients. Additionally, intercellular communication between tumor cells and other non-tumor cells is markedly enhanced in astrocytoma samples from epileptic patients. CONCLUSION: This study provides evidence of a genetic association between epilepsy and gliomas and elucidates the biological mechanisms through which epilepsy may influence glioma progression.

Humans↗