Gene Expression In Response Research Articles

Loss of the PPE71-esxX-esxY-PPE38 locus drives adaptive transcriptional responses and hypervirulence of Mycobacterium tuberculosis lineage 2.

Mycobacterium tuberculosis (M.tb) is remarkable for its immense global disease burden and low mutation rate. Despite strong selective pressure, M.tb shows frequent deletions at the PPE71-38 locus, most notably in hypervirulent L2 Beijing strains. Here, we show that loss of the PPE71-38 locus causes increased stress response gene expression and increased triglyceride levels. In addition, we demonstrate that reintroduction of PPE71 into the L2 strain HN878 suppresses the baseline elevation of these transcripts, while overexpression of PPE71 increases the localization of PE_PGRS proteins and lipoproteins to the M.tb outer mycomembrane. Mouse infection confirmed the hypervirulence of the PPE71-38 deletion strain and conversely showed that PPE71 overexpression attenuates M.tb. Our results indicate that loss of PPE71-38 is sufficient to drive an adaptive transcriptional response seen in M.tb L2 strains that likely contributes to the hypervirulence of this lineage.

A Study on the Impact of α-Fe2O3 NPs, Biochar, and Their Composite Treatments on the Gene Expression Response of Muskmelon under Cadmium Pollution

A Study on the Impact of α-Fe2O3 NPs, Biochar, and Their Composite Treatments on the Gene Expression Response of Muskmelon under Cadmium Pollution

Comparative analysis of rapid alkalinization factor peptide-triggered plant immunity in citrus and closely related species.

Comparative analysis of rapid alkalinization factor peptide-triggered plant immunity in citrus and closely related species.

Substrate stiffness modifies gene expression and transcriptional response of equine endometrial fibroblasts to TGF-β1.

Substrate stiffness modifies gene expression and transcriptional response of equine endometrial fibroblasts to TGF-β1.

Heterologous overexpression of the Suaeda glauca stress-associated protein (SAP) family genes enhanced salt tolerance in Arabidopsis transgenic lines.

Heterologous overexpression of the Suaeda glauca stress-associated protein (SAP) family genes enhanced salt tolerance in Arabidopsis transgenic lines.

Protein to biomaterials: Unraveling the antiviral and proangiogenic activities of Ac-Tβ1-17 peptide, a thymosin β4 metabolite, and its implications in peptide-scaffold preparation.

Protein to biomaterials: Unraveling the antiviral and proangiogenic activities of Ac-Tβ1-17 peptide, a thymosin β4 metabolite, and its implications in peptide-scaffold preparation.

Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma Based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.

Hepatocellular Carcinoma (HCC) is closely linked to inflammatory reactions, with chronic liver diseases acting as major risk factors. In the inflammatory microenvironment, repeated damage and repair of liver cells lead to genetic mutations, abnormal proliferation, and tumorigenesis. This study aimed to investigate the expression profile of specific cell clusters under inflammatory stimulation in HCC and identify potential therapeutic drugs. Comprehensive analysis of HCC transcriptome data and single-cell sequencing data from TCGA, ICGC, and GEO databases was conducted to explore the specific molecular mechanisms of epithelial cells. Virtual screening of natural compounds in the ZINC database and in vitro cell experiments were performed to identify drugs that regulate the expression of inflammatory factors in epithelial cells. Analysis of the single-cell dataset revealed cell clusters closely associated with HCC, notably Epithelial cells, Hepatocytes, MSC, and iPS cells, with Epithelial cells playing a pivotal role in HCC development. Further investigation of TCGA data unveiled 83 differentially expressed genes (DEGs) related to inflammatory responses in HCC. Intersection analysis of DEGs in epithelial cells and HCC DEGs identified 12 common DEGs, including ADRM1, ATP2B1, FZD5, GPC3, KIF1B, KLF6, LY6E, MET, NAMPT, SERPINE1, SPHK1, and SRI. Prognostic analysis revealed that CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP were influential in the survival prognosis of HCC. A prognostic model based on the expression levels of these genes demonstrated an increased risk of HCC associated with higher differential expression of inflammatory response genes. Additionally, molecular dynamics simulations indicated that compounds NADH and Deferoxamine formed stable docking models with the inflammatory protein VIP, suggesting their potential as candidates for targeted therapy. Inflammatory factors CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP influence the inflammatory cascade response in HCC epithelial cells, and their expression correlates with the survival prognosis of HCC patients. Interfering with VIP expression effectively suppresses proliferation, migration, and invasion of HCC cells, as well as inhibiting the occurrence of inflammatory cascade reactions, thus slowing down the progression of hepatocellular carcinoma. Furthermore, compounds NADH and Deferoxamine have the potential to target and bind to the inflammatory protein VIP, highlighting their relevance in potential HCC treatment.

RNA-binding proteins as key regulators in pulmonary diseases: A review.

RNA-binding proteins as key regulators in pulmonary diseases: A review.

Effects of maternal smoking on inflammation, autophagy/mitophagy, and miRNAs in endothelial cells: Influence of newborn sex.

Effects of maternal smoking on inflammation, autophagy/mitophagy, and miRNAs in endothelial cells: Influence of newborn sex.

Implication of environmental factors on the pathogenicity of Vibrio vulnificus: Insights into gene activation and disease outbreak.

Implication of environmental factors on the pathogenicity of Vibrio vulnificus: Insights into gene activation and disease outbreak.

Integration of bioaccumulations, chemical forms and gene expression responses to understand the transformation and detoxification of inorganic arsenic, cadmium and lead in the brown seaweed Sargassum fusiforme.

Integration of bioaccumulations, chemical forms and gene expression responses to understand the transformation and detoxification of inorganic arsenic, cadmium and lead in the brown seaweed Sargassum fusiforme.

Corneal Edema and the Endothelium in Spaceflight

INTRODUCTION: With future manned missions that extend beyond low Earth orbit, it would be wise to anticipate all risks to astronaut health, including those relevant to ophthalmology and the ocular surface. Corneal edema has been documented among mice experiments conducted onboard the Space Transportation System mission, STS-133, owing to increased stress response gene expression. METHODS: A targeted, relevant search of the literature on topics relating to ocular surface and spaceflight was conducted with scholarly databases PubMed, Web of Science, and Embase from inception to July 2024. RESULTS: From our search results we identified 12,742 articles, 485 of which met the scope of our initial literature search criteria. Following refinement, 99 articles were included in our review paper. The most frequently mentioned mechanisms of corneal edema related to spaceflight included contact lens related hypoxia (24%). Regarding treatments for corneal edema, surgical grafts (16.9%) were most common. From our data, central corneal thickness measurements in astronauts with prior refractive surgery showed no significant differences pre- and postflight: right eye mean preflight, 492 µm vs. postflight, 493.3 µm; left eye, 499 µm pre- and postflight. DISCUSSION: This knowledge may contribute to our understanding of the increased risk of ocular surface symptoms reported among astronauts. This review discusses the current literature on corneal endothelial transport physiology and the detriments of corneal edema to astronaut visual function. We also describe the diagnostic modalities we can apply to spaceflight, such as anterior segment optical coherence tomography, and offer convenient countermeasures to spaceflight-related ocular surface anomalies. In doing so, we aim to make future missions safer for human exploration. Lee R, Ong J, Sampige R, Panzo N, Memon H, Suh A, Waisberg E, Mader T, Berdahl J, Chévez-Barrios P, Lee AG. Corneal edema and the endothelium in spaceflight. Aerosp Med Hum Perform. 2025; 96(7):569–577.

Mechanism by which hydrogen-rich water mitigates exercise-induced fatigue: activation of the immunoresponsive gene 1-itaconate/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

JOURNAL/mgres/04.03/01612956-202603000-00005/figure1/v/2025-06-28T140100Z/r/image-tiff Exercise-induced fatigue limits athletic performance. Molecular hydrogen is an effective treatment for relieving fatigue, but the exact mechanism is not clear. In our study, a mouse model of fatigue was established to explore the molecular mechanism by which hydrogen-rich water reduces exercise-induced fatigue. The results showed that hydrogen-rich water improved the motor function of fatigue mice, reduced the levels of fatigue-related biomarkers (blood urea nitrogen, lactate, and creatine kinase), and alleviated gastrocnemius muscle injury. Furthermore, ultrahigh-performance liquid chromatography-mass spectrometry revealed that hydrogen-rich water upregulated the expression of immune response gene 1 (IRG1), increased the abnormally reduced levels of itaconic acid due to fatigue, and subsequently activated the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Finally, C2C12 cells exposed to an IRG1 inhibitor (IRG1-IN) or 4-octyl itaconic acid (4-OI) were treated with hydrogen-rich water, indicating that hydrogen-rich water effectively upregulated the expression of Nrf2 and HO-1 in cells. In summary, hydrogen-rich water alleviates exercise-induced fatigue by activating the IRG1-itaconic acid/Nrf2/HO-1 pathway and inhibiting oxidative stress.

Effects of water temperature increase on gene expression, biochemical, and histopathological responses of the bivalve species Mytilus galloprovincialis to the antineoplastic drug 5-fluorouracil.

Effects of water temperature increase on gene expression, biochemical, and histopathological responses of the bivalve species Mytilus galloprovincialis to the antineoplastic drug 5-fluorouracil.

Effects of Microplastics on Gene Expression, Muscular Performance, and Immunological Responses in Nile Tilapia (Oreochromis niloticus): Seasonal and Habitat Variations

Microplastics (MPs; less than 5 mm in size) are becoming increasingly prevalent in both terrestrial and aquatic ecosystems. As these particles enter the food chain, they have the potential to pose significant risks to human health. However, their effects on vital fish tissues, such as skeletal muscle, are not yet fully understood. In this study, we examined Nile tilapia (Oreochromis niloticus) from two distinct sites on the Nile River in Egypt: the Nile branch (Damietta branch) and Riah El-Towfiqi. Using Fourier Transform Infrared Spectroscopy (FTIR) and histological study, we confirmed the presence of MPs in both gastrointestinal and muscle tissues. We focused on understanding how MPs might affect fish muscle by investigating the expression of genes involved in muscle atrophy and hypertrophy using Real Time-PCR and histological alterations in muscle tissues of tilapia collected from the two studied sites in the four seasons. Our results revealed histological alterations in muscle tissues collected from the two sites studied in the four seasons. The expression levels of atrophy-related genes, Atrogin-1 (Fbxo32), Capn-1, and the apoptosis marker Caspase3a (Casp3a), showed increased expression, especially during the summer at both sites. On the other hand, the hypertrophy-related gene Igf-1 exhibited a significant decrease while, muscle stem cell genes (Pax3, Pax7) and muscle differentiation gene markers (Myf5, Mrf6) displayed seasonal upregulation, with heightened activity during winter and summer, depending on the location. Additionally, immune-related genes (Ccr9, Irak4, Igl-1, Tlr1) demonstrated notable seasonal changes, with a peak during summer at the Nile branch. These findings demonstrate that MPs can disrupt muscle integrity and immune function in fish, with implications for ecosystem health and potential risks to human food security.

Integrative Multi-Omic and Immune Profiling of Lung Adenocarcinoma: Molecular Landscapes, Gene Expression, and Treatment Response Insights.

Lung adenocarcinoma (LUAD) is a major cause of cancer death. Traditional histopathological classification overlooks molecular heterogeneity, limiting personalized treatment. This study used multiomic data to define LUAD subtypes, assess prognostic significance, and analyze immune features, aiming to improve targeted therapy and clinical outcomes. This study used Consensus Clustering and Gap Statistics to analyze LUAD multiomic data, including mRNA, lncRNA, miRNA, DNA methylation, and mutations. Clustering was validated by silhouette plots and heatmaps. Molecular characterization involved regulon activity, immune and metabolic profiling. Functional assays (qPCR, WB, CCK-8, flow cytometry) assessed NDNF's role in LUAD. Two molecular LUAD subtypes showed distinct clustering and survival outcomes. One subtype had worse prognosis and unique immune features, including checkpoint expression and microenvironment differences. Gene signatures and metabolism varied by subtype. NDNF was downregulated in tumors; its overexpression suppressed LUAD cell viability and promoted apoptosis, suggesting tumor-suppressive function. This study identifies two LUAD subtypes with distinct molecular and immune features linked to prognosis and therapy response. NDNF downregulation and its tumor-suppressive effects highlight its therapeutic potential. These findings support improved LUAD stratification and personalized treatment strategies. This study reveals two LUAD molecular subtypes with distinct prognoses and immune features, offering a basis for more precise treatment strategies. The identification of NDNF as a potential tumor suppressor suggests its value as both a biomarker and therapeutic target. These findings support improved LUAD stratification and personalized therapy.

Post-Transcriptional Regulation of the MiaA Prenyl Transferase by CsrA and the Small RNA CsrB in Escherichia coli

MiaA is responsible for the addition of the isopentyl modification to adenine 37 in the anticodon stem loop of specific tRNAs in Escherichia coli. Mutants in miaA have pleotropic effects on the cell in E. coli and play a role in virulence gene regulation. In addition, MiaA is necessary for stress response gene expression by promoting efficient decoding of UUX-leucine codons, and genes with elevated UUX-leucine codons may be a regulatory target for i6A-modified tRNAs. Understanding the temporal nature of the i6A modification status of tRNAs would help us determine the regulatory potential of MiaA and its potential interplay with leucine codon frequency. In this work, we set out to uncover additional information about the synthesis of the MiaA. MiaA synthesis is primarily driven at the transcriptional level from multiple promoters in a complex operon. However, very little is known about the post-transcriptional regulation of MiaA, including the role of sRNAs in its synthesis. To determine the role of small RNAs (sRNAs) in the regulation of miaA, we constructed a chromosomal miaA-lacZ translational fusion driven by the arabinose-responsive PBAD promoter and used it to screen against an Escherichia coli sRNA library (containing sRNAs driven by the IPTG-inducible PLac promoter). Our genetic screen and quantitative β-galactosidase assays identified CsrB and its cognate protein CsrA as potential regulators of miaA expression in E. coli. Consistent with our hypothesis that CsrA regulates miaA post-transcriptional gene expression through binding to the miaA mRNA 5′ UTR, and CsrB binds and regulates miaA post-transcriptional gene expression through sequestration of CsrA levels, a deletion of csrA significantly reduced expression of the reporter fusion as well as reducing miaA mRNA levels. These results suggest that under conditions where CsrA is inhibited, miaA mRNA translation and thus MiaA-dependent tRNA modification may be limited.

Trans-regulatory loci shape natural variation of gene expression plasticity in Arabidopsis.

Organisms regulate gene expression in response to environmental cues, a process known as plasticity, to adjust to changing environments. Research into natural variation and the evolution of plasticity frequently studies cis-regulatory elements with theory suggesting they are more important evolutionarily than trans-regulatory elements. Genome-wide association studies have supported this idea, observing a predominance of cis-loci affecting plasticity. However, studies in structured populations provide a contrasting image, raising questions about the genetic architecture of natural variation in plasticity. To circumvent potential statistical difficulties present in genome-wide association studies, we mapped loci underlying transcriptomic plasticity in response to salicylic acid using recombinant inbred lines generated from two random Arabidopsis thaliana accessions. We detected extensive transgressive segregation in the salicylic acid response, suggesting that plasticity to salicylate in Arabidopsis is polygenic. Most loci (>75%) underlying this variation act in trans, especially for loci influencing plasticity. Trans-acting loci were enriched in genome hotspots, with predominantly small effect sizes distributed across many genes. This could potentially explain their under-discovery in genome-wide association studies. This work reveals a potentially important role for trans-acting loci in plastic expression responses, with implications for understanding plant adaptation to different environments.

Measuring cytokines in Eurasian tundra reindeer (Rangifer tarandus tarandus) with a bovine bead-based multiplex immunoassay and real-time PCR

BackgroundReindeer (Rangifer tarandus tarandus) herding is based on access to seasonal pastures. Pastureland is, however, being lost and fragmented due to e.g. climate change, human activities, and predators, creating an increasing need for feeding and fencing. This alters disease occurrence, leading to a greater need for disease investigation tools. Knowledge of the activation of immune pathways during disease can be obtained by measuring cytokines, but no commercial methods are currently available for reindeer. This study investigated whether the MILLIPLEX® Bovine Cytokine Magnetic Bead assay could be used to detect interleukin (IL)-6, IL-8, IL-10, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in reindeer cell supernatants and serum. Peripheral blood mononuclear cells (PBMCs) from reindeer (n = 4) and cattle (Bos taurus, n = 3) were stimulated with mitogens for 6 and 24 h (h) and the quantity of cytokines in cell supernatants was measured. Serum from experimental viral infections in reindeer (Orf virus; ORFV and Varicellovirus cervidalpha2; CvHV2) was also analysed. Additionally, primers were designed to measure cytokine gene expression in response to mitogens by real-time polymerase chain reaction (qPCR). ResultsThe bovine bead-based multiplex immunoassay detected five of six cytokines (IL-8, IL-10, IL-17, TNF-α, IFN-γ) in reindeer PBMC supernatants after stimulation. All cytokines were detected in bovine samples. Although cytokine concentrations were generally higher in bovine samples, analysis of reindeer supernatants demonstrated significantly increased IL-10, IL-17, TNF-α and IFN-γ concentrations in supernatants from stimulated compared to unstimulated PBMCs. Neither reindeer nor cattle samples showed a significant increase for IL-6, while IL-8 was increased only in bovine samples after 6 h stimulation. Serum from reindeer infected with CvHV2 showed significantly increased IFN-γ levels on days 4 and 7 post inoculation. Gene expression of all cytokines was increased by stimulation of reindeer PBMCs, except IL-6 for which primer design was unsuccessful.ConclusionsThis study shows the potential of the bovine bead-based multiplex immunoassay for measuring IL-10, IL-17, TNF-α, and IFN-γ concentrations in reindeer. The qPCR is suitable for measuring gene expression of these cytokines and IL-8. These methods may be used to characterise immune responses in reindeer, but further testing and validation are warranted.

CqHKT1 and CqSOS1 mediate genotype-dependent Na+ exclusion under high salinity conditions in quinoa.

Salinity threatens crop production worldwide, and salinized areas are steadily increasing. As most crops are sensitive to salt, there is a need to improve the salt tolerance of major crops and promote the cultivation of under-utilized salt-tolerant crops. Quinoa, a pseudocereal and leafy vegetable from the Andean region of South America, is highly salt-tolerant, thrives in marginal environments, and has excellent nutritional properties. Research has often focused on epidermal bladder cells, a feature of quinoa thought to contribute to salt tolerance; however, recent evidence suggests that these cells are not directly involved. The salt tolerance mechanism in quinoa remains unclear. Here, we show genotype-dependent differences in Na+ and K+ accumulation mechanisms using representative 18 lines of three genotypes by focusing on young quinoa seedlings at a stage without epidermal bladder cells. High salinity (600 mM NaCl) did not affect the early growth of all three quinoa genotypes. Under high salinity conditions, lowland quinoa lines tended to accumulate more Na+ in their aerial parts than highland lines did. By contrast, K+ accumulation was slightly reduced in the aerial parts but significantly decreased in the roots of all the genotypes. Resequencing of 18 quinoa lines supports the notion that genotype determines aboveground Na+ uptake and gene expression in response to high salinity. Using virus-induced gene silencing, we further demonstrated that CqHKT1 and CqSOS1 mediate Na+ exclusion in quinoa. These findings provide insight into salt tolerance mechanisms, serving as a basis for improving crop production under high salinity conditions.