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PubMed2005

The YJR127C/ZMS1 gene product is involved in glycerol-based respiratory growth of the yeast Saccharomyces cerevisiae.

A putative yeast mitochondrial upstream activating sequence (UAS) was used in a one-hybrid screening procedure that identified the YJR127C ORF on chromosome X. This gene was previously designated ZMS1 and is listed as a transcription factor on the SGD website. Real time RT-PCR assays showed that expression of YJR127C/ZMS1 was glucose-repressible, and a deletion mutant for the gene showed a growth defect on glycerol-based but not on glucose- or ethanol-based medium. Real time RT-PCR analyses identified severely attenuated transcript levels from GUT1 and GUT2 to be the source of that growth defect, the products of GUT1 and GUT2 are required for glycerol utilization. mRNA levels from a large group of mitochondria- and respiration-related nuclear genes also were shown to be attenuated in the deletion mutant. Importantly, transcript levels from the mitochondrial OLI1 gene, which has an associated organellar UAS, were attenuated in the DeltaYJR127C mutant during glycerol-based growth, but those from COX3 (OXI2), which lacks an associated mitochondrial UAS, were not. Transcriptome analysis of the glycerol-grown deletion mutant showed that genes in several metabolic and other categories are affected by loss of this gene product, including protein transport, signal transduction, and others. Thus, the product of YJR127C/ZMS1 is involved in transcriptional control for genes in both cellular genetic compartments, many of which specify products required for glycerol-based growth, respiration, and other functions.

Cell Respiration↗
PubMed2025

Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma.

Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.

Lymphangiogenesis↗
PubMed2025

Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.

Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.

Animals↗
PubMed2025

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling.

PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs). METHODS: The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-α secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs. RESULTS: Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-α secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-α secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-α secretion from IFIH1 R779H-mutated DCs. CONCLUSION: Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.

Humans↗
PubMed2006

Characterization of an Arabidopsis thaliana mutant lacking a cytosolic non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase.

Non-phosphorylating glyceraldehyde- 3-phosphate dehydrogenase (NP-GAPDH) is a conserved cytosolic protein found in higher plants. In photosynthetic cells, the enzyme is involved in a shuttle transfer mechanism to export NADPH from the chloroplast to the cytosol. To investigate the role of this enzyme in plant tissues, we characterized a mutant from Arabidopsis thaliana having an insertion at the NP-GAPDH gene locus. The homozygous mutant was determined to be null respect to NP-GAPDH, as it exhibited undetectable levels of both transcription of NP-GAPDH mRNA, protein expression and enzyme activity. Transcriptome analysis demonstrated that the insertion mutant plant shows altered expression of several enzymes involved in carbohydrate metabolism. Significantly, cytosolic phosphorylating (NAD-dependent) glyceraldehyde-3-phosphate dehydrogenase mRNA levels are induced in the mutant, which correlates with an increase in enzyme activity. mRNA levels and enzymatic activity of glucose-6-phosphate dehydrogenase were also elevated, correlating with an increase in NADPH concentration. Moreover, increased ROS levels were measured in the mutant plants. Down-regulation of several glycolytic and photosynthetic genes suggests that NP-GAPDH is important for the efficiency of both metabolic processes. The results presented demonstrate that NP-GAPDH has a relevant role in plant growth and development.

Arabidopsis↗
PubMed2005

Arabidopsis thaliana full genome longmer microarrays: a powerful gene discovery tool for agriculture and forestry.

Sequenced plant genomes provide a large reservoir of known genes with potential for use in crop and tree improvement, but assignment of specific functions to annotated genes in sequenced plant genomes remains a challenge. Furthermore, most plant genes belong to families encoding proteins with related but distinct functions. In this commentary, we discuss our development of Arabidopsis spotted whole genome longmer oligonucleotide microarrays, and their use in global transcription profiling. We show that longmer array based transcriptome analysis in Arabidopsis can be used as an efficient and effective gene discovery and functional genomics tool, particularly for functional analyses of members of large gene families. We discuss experiments that focus on gene families involved in phenylpropanoid natural product biosynthesis and fiber differentiation. These analyses have helped to elucidate functions of individual gene family members, and have identified new candidate genes involved in fiber development and differentiation. Results obtained by these studies in Arabidopsis can be used as the basis for gene discovery in commercially important plants, and we have focused our attention on Populus trichocarpa (poplar), a species important in forestry and agroforestry for which complete genome sequence information is available.

Agriculture↗
PubMed2026

Synthesis of Padina boergesenii-Derived Zinc Oxide Nanoparticles and their Therapeutic Potential Against Oral Squamous Cell Carcinoma: A Transcriptomic and in Vitro Evaluation.

Cancer remains a major health challenge, with oral squamous cell carcinoma (OSCC) being an high aggressive subtype of head and neck squamous cell carcinoma that lacks effective therapeutic options. Current study integrates the synthesis of zinc oxide nanoparticles (ZnO-NPs) from the marine brown algae Padina boergesenii with the OSCC gene expression profile to evaluate their potential therapeutic effects against OSCC. Herein, the ZnO-NPs from Padina boergesenii were prepared through the green synthesis method. The obtained ZnO-NPs were characterized through spectroscopic methods, the UV spectrophotometer shows maximum absorbance at 372 nm, FT-IR presents Zn-O functional band at 516 cm- 1, HR-TEM confirms average particle size of 55.70 nm and the Zetasizer shows zeta potential of + 12.9 mV, indicating colloidal stability. The cytotoxicity assay with ZnO-NPs against oral cancer cell lines exhibited a reduction in cell viability at IC₅₀ value of 20 µg/mL. Meanwhile, the transcriptome analysis of OSCC highlights that MYC, STAT3, BRCA1, and AKT1 are the OSCC therapeutic targets involved in proliferation, immune evasion, genomic instability, and cancer signalling pathways. Further, qRT-PCR based gene expression analysis demonstrates significant down-regulation of these targets upon ZnO-NPs treatment in KB cell lines. Overall, this study emphasizes the anticancer potential of Padina boergesenii-derived ZnO-NPs that could effectively modulate the therapeutic targets and may benefit the treatment of OSCC cancer.

Cytotoxicity↗
PubMed2004

Mitochondrial disease in flies.

The Drosophila mutant technical knockout (tko), affecting the mitochondrial protein synthetic apparatus, exhibits respiratory chain deficiency and a phenotype resembling various features of mitochondrial disease in humans (paralytic seizures, deafness, developmental retardation). We are using this mutant to analyse the cellular and genomic targets of mitochondrial dysfunction, and to identify ways in which the phenotype can be alleviated. Transgenic expression of wild-type tko in different patterns in the mutant background reveals critical times and cell-types for production of components of the mitochondrial disease-like phenotype. Mitochondrial bioenergy deficit during the period of maximal growth, as well as in specific parts of the nervous system, appears to be most deleterious. Inbreeding of tko mutant lines results in a systematic improvement in all phenotypic parameters tested. The resulting sub-lines can be used for genetic mapping and transcriptomic analysis, revealing clues as to the genes and pathways that can modify mitochondrial disease-like phenotypes in a model metazoan.

Animals↗
PubMed2026

Selenium nanoparticle synthesis in Stenotrophomonas maltophilia: Mutagenesis and molecular mechanisms.

Biosynthetic selenium nanoparticles (SeNPs) exhibit superior bioavailability and detoxification potential compared to inorganic selenium forms. In this study, the strain Stenotrophomonas maltophilia SE5, isolated from the feces of piglets (Duroc × Large White × Landrace), was utilized as the wild-type strain and subjected to atmospheric and room temperature plasma (ARTP) mutagenesis. A high-yielding mutant, Mu537, was successfully obtained, which exhibited an enhanced tolerance to sodium selenite, with its maximum tolerable concentration increasing from 1.0 g/L to 1.5 g/L. After 48 h of cultivation, Mu537 achieved an approximate 35% increase in SeNPs conversion rate and a 40% increase in SeNPs concentration relative to the parental strain. Integrated whole-genome sequencing and transcriptomic analysis revealed that pivotal genes associated with efficient SeNPs biosynthesis, including cysB, trxA, and sufE, were significantly up-regulated. These findings provide a systematic understanding of the potential molecular mechanisms driving enhanced SeNPs biosynthesis, offering both high-quality microbial resources and theoretical support for the industrial production of SeNPs.

Stenotrophomonas maltophilia↗
PubMed2026

An allograft inflammatory factor enhances sperm viability by modulating intracellular calcium in oyster Crassostrea gigas.

As an important aquaculture bivalve, the Pacific oyster Crassostrea gigas faces severe constraints in artificial reproduction, where low sperm motility often leads to fertilization failure and limits the sustainable development of the oyster aquaculture industry. In the present study, the variation of sperm from different oyster individuals was observed, and high-quality sperm possessed intact, elongated flagella with no structural abnormalities, while low-quality sperm showed shortened flagella with frequent tangling or coiling defects. Transcriptomic analysis comparing high- and low-quality sperm revealed significantly reduced expression of genes associated with sperm motility and release (CgAIF1, CgAchR, CgSEX), sperm quality and development (CgEP4, CgIFi2b), and cryoprotection (CgISPs) in low-quality sperm. Notably, an allograft inflammatory factor (designed as CgAIF1) encoding EF-hand domain, known as Ca2+ binding activity, was among the most significantly downregulated in low-motility sperm. CgAIF1 is highly expressed in haemocytes, ganglia, and gonads of oysters. Incubation with the recombinant AIF1 protein (rCgAIF1) significantly improved sperm curvilinear velocity, thereby enhancing the overall motility of C. gigas sperm. Furthermore, rCgAIF1 incubation increased intracellular Ca2+ levels (2.13-fold at 30 min, 2.71-fold at 60 min) and superoxide dismutase (SOD) activity (1.44-fold at 30 min, 1.24-fold at 60 min) in sperm, suggesting potential roles in calcium homeostasis regulation and antioxidant defense. In conclusion, this study demonstrates that CgAIF1 significantly enhances motility of oyster sperm, providing a scientific basis for artificial breeding and seed production in oyster aquaculture.

Animals↗
PubMed2006

Pyocyanin isolated from a marine microbial population: synergistic production between two distinct bacterial species and mode of action.

Marine microbial populations collected from the Hawaiian Islands were screened for antimicrobial activity. A blue metabolite was identified from mixed cell cultures, but production was not evident in pure cultures. Experiments designed to probe the synergistic role of the microorganisms are presented. Full characterization of the blue natural product, pyocyanin, is provided including corrections made to 1H and 13C-NMR assignments of the molecule misreported in the chemical literature and yeast transcriptome analysis. The transcriptional effects were consistent with the compound's purported role as an inducer of oxidative stress and damage and illustrates the overall potential of the method to reveal the primary biological/cellular effects of a natural product. The experiments outlined here might serve as a general paradigm for identification of natural products arising from microbial communities and investigation of their respective interactions.

Bacteria↗
PubMed2025

Liquid Biopsy-Multiomics Link Adhesion Pathway Dysregulation to Kidney Injury Severity.

INTRODUCTION: Severe acute kidney injury (AKI) is strongly associated with the risk of developing chronic kidney disease; however, little is known about the cell type-specific mechanisms driving kidney injury severity. METHODS: In this multicenter observational study, we used clinically obtained liquid biopsy proteomics and machine learning (ML) to predict severe outcomes in patients with COVID-associated and non-COVID AKI. Further, we orthogonally combined 169 urine proteomics with 437 plasma proteomics samples and 40 urine sediment single-cell transcriptomics samples to identify complementary dysregulated mechanisms. RESULTS: Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrate predictive power for both discovery and validation set with AUC of 87% and 76%, respectively. These predictive proteomics features obtained demonstrate that cell adhesion and autophagy-associated pathways are uniquely impacted in severe AKI. Differentially abundant proteins (DAPSs) associated with these pathways are highly expressed in cells of the juxtamedullary nephron, endothelial cells (ECs), and podocytes, indicating that these kidney cell types could be potential targets. Single-cell transcriptomic analysis in the in vitro model of kidney organoids infected with SARS-CoV-2 reveal dysregulation of extracellular matrix (ECM) organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters shows significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. CONCLUSION: Collectively, these data suggest that ECM degradation and adhesion-associated mechanisms could be the main driver of severe kidney injury.

AKI↗
PubMed2024

Decoding the trajectory of antibiotic resistance genes in saline and alkaline soils: Insights from different fertilization regimes.

The soil salinity and alkalinity play an important role in the occurrence and proliferation of antibiotic resistance genes (ARGs). Yet, little is known the underlying mechanism by which soil salinity and alkalinity affect antibiotic resistance evolution. Here we investigated the ARGs variation in soil salinity and alkalinity environments created by different fertilization, and explored the biological mechanisms that salinity and alkalinity alter the evolutionary paradigm of antibiotic resistance. The results showed the soil treated by organic fertilizer exhibited a low salinity, neutral level (TSD 239.20 μS/cm, pH 7.17). The ARG abundance in the OF treatment was the highest, keeping an average of 67.83 TPM. Beside the effect of direct input of organic fertilizer at the beginning, it was important to note that, ARGs abundance during planting showed significant correlations with pH and electric conductivity. We observed that changes in microbial survival strategies under different salinity and alkalinity conditions further affected ARG hosts abundance. Indoor experiments demonstrated that there was a survival trade-off between the growth of resistant bacteria and the evolution of antibiotic resistance in salinity and alkalinity environments. Meta-genomic and Meta-transcriptomic analysis consistently demonstrated bacterial antibiotic resistance was primarily associated with pyruvate, energy and lipid metabolic pathways. The functional gene related to salinity and alkalinity, like cysH, cysK, plsB and plsC showed negative correlations with MDR. Prokaryotic transcription assays validated these relations. This study well explains the prevalence of soil ARGs after different fertilization regimes and will give a deeper understanding for the effect of soil salinity and alkalinity on antibiotic resistance evolution.

Soil↗
PubMed2006

Extensive adenosine-to-inosine editing detected in Alu repeats of antisense RNAs reveals scarcity of sense-antisense duplex formation.

One type of RNA editing converts adenosine residues to inosine in double-stranded regions. Recent transcriptome analysis has revealed that numerous Alu repeats, present within introns and untranslated regions of human transcripts, are subject to this A-->I RNA editing. Furthermore, it revealed global transcription of antisense RNAs. Here, we demonstrate that antisense RNAs are also edited extensively but only in their Alu repeat sequences, and editing does not extend to the surrounding sequence. Our findings imply that sense and antisense RNAs form two separate intramolecular double-stranded RNAs consisting of inversely oriented Alu repeats, but rarely form intermolecular duplexes.

Adenosine↗
PubMed2004

Genetic evidence for histidine kinase HP165 being an acid sensor of Helicobacter pylori.

Helicobacter pylori is a human gastric pathogen which is extremely well adapted to its unique habitat. Crucial for the survival under the acidic conditions prevailing in the stomach is the enzyme urease. Transcriptome analysis has shown that transcription of a large number of genes responds to the exposure of H. pylori to acid including the genes encoding the urease subunits UreA and UreB as well as several genes which have been previously identified as target genes of the two-component system HP166-HP165. Here, we provide genetic evidence that a stimulus perceived by the histidine kinase HP165 is pH since increased transcription at acidic pH from the promoters controlling the expression of the ORFs hp119 and hp1432 which belong to the HP166-HP165 regulon is strictly dependent on the presence of histidine kinase HP165. Furthermore, we show that the basal transcription from the promoter of the ureA gene is modulated by the HP166-HP165 two-component system in response to acidic pH. On the other hand, the acid-induced increase in transcription of the promoter directing the expression of the orphan response regulator HP1021 is not controlled by the HP166-HP165 two-component system, nor is it mediated by HP1021 itself.

Acids↗
PubMed2005

Non-coding RNAs: new players in eukaryotic biology.

The completion of the human, mouse and other eukaryotic genomes were important scientific milestones, but they were just small steps towards the understanding of eukaryotic biology. Recent transcriptome analysis and different experimental approaches have identified a surprisingly large number of non-coding RNAs (ncRNAs) in eukaryotic cells. ncRNAs comprise microRNAs, anti-sense transcripts and other Transcriptional Units containing a high density of stop codons and lacking any extensive "Open Reading Frame". They have been shown to regulate gene expression by novel mechanisms such as RNA interference, gene co-suppression, gene silencing, imprinting and DNA demethylation. It is becoming clear that these novel RNAs perform critical functions during development and cell differentiation. There is also mounting evidence of their involvement in cancer and neurological diseases. Together, all this information indicates that ncRNAs are emerging as a new class of functional transcripts in eukaryotes. Therefore, great challenges lie in the years ahead: understanding the molecular biology of higher organisms will require revealing all proteins (Proteome), all ncRNAs (RNome) and their interactions (Interactome) in the complex molecular scenario within eukaryotic cells.

Animals↗
PubMed2005

Using the transcriptome to annotate the genome revisited: application of massively parallel signature sequencing (MPSS).

Transcriptome analysis can provide useful data for refining genome sequence annotation. Application of massively parallel signature sequencing (MPSS) revealed reproducible transcription, in multiple MPSS cycles, from 73% of computationally predicted genes in the Theileria parva schizont lifecycle stage. Signatures spanning consecutive exons confirmed 142 predicted introns. MPSS identified 83 putative genes, >100 codons overlooked by annotation software, and 139 potentially incorrect gene models (with either truncated ORFs or overlooked exons) by interfacing signature locations with stop codon maps. Twenty representative models were confirmed as likely to be incorrect using reverse transcription PCR amplification from independent schizont cDNA preparations. More than 50% of the 60 putative single copy genes in T. parva that were absent from the genome of the closely related T. annulata had MPSS signatures. This study illustrates the utility of MPSS for improving annotation of small, gene-rich microbial eukaryotic genomes.

Animals↗
PubMed2006

Cloning and characterization of cDNAS encoding carboxypeptidase-like proteins from the gut of Hessian fly larvae [Mayetiola destructor (Say)].

Transcriptomic analysis of the gut from Hessian fly larvae [Mayetiola destructor (Say)] identified nine cDNA clones that encode different carboxypeptidase-like proteins. Sequence comparison revealed that five of the nine cDNAs encoded very similar proteins with amino acid sequence identity over 96%. The other four cDNAs encoded diversified proteins with amino acid sequence identity less than 60%. Further sequence comparison with well characterized carboxypeptidases from other organisms revealed that these cDNAs encoded MDCP (M. destructor carboxypeptidase)-A1, MDCP-A2, MDCP-B, MDCP-BL, and MDCP-D. All residues characteristic of metallocarboxypeptidases including the HXXE motif were conserved among members. Northern blot analysis revealed various expression patterns for different gene groups in different developmental stages of M. destructor, suggesting that individual carboxypeptidases perform specific functions or have different specificities. Enzymatic activity assays demonstrated that both carboxypeptidases A and B are predominant in the larval stage, the only feeding stage of M. destructor, indicating a role in food digestion. The digestive role is further supported by the fact that 80% of the enzymatic activity in larvae occurred in the gut. Among these two types of enzymes, the activity of carboxypeptidase A was at least four times higher than that of carboxypeptidase B under the same conditions, suggesting that carboxypeptidase A is the major digestive enzyme in the gut of M. destructor larvae.

Amino Acid Sequence↗