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Aconitum carmichaelii is an important medicinal herb used widely in China, Japan, India, Korea, and other Asian countries. While extensive research on the characterization of metabolic extracts of A. carmichaelii has shown accumulation of numerous bioactive metabolites including aconitine and aconitine-type diterpene alkaloids, its biosynthetic pathway remains largely unknown. Biosynthesis of these secondary metabolites is tightly controlled and mostly occurs in a tissue-specific manner; therefore, transcriptome analysis across multiple tissues is an attractive method to identify the molecular components involved for further functional characterization. In order to understand the biosynthesis of secondary metabolites, Illumina-based deep transcriptome profiling and analysis was performed for four tissues (flower, bud, leaf, and root) of A. carmichaelii, resulting in 5.5 Gbps clean RNA-seq reads assembled into 128,183 unigenes. Unigenes annotated as possible rate-determining steps of an aconitine-type biosynthetic pathway were highly expressed in the root, in accordance with previous reports describing the root as the accumulation site for these metabolites. We also identified 21 unigenes annotated as cytochrome P450s and highly expressed in roots, which represent candidate unigenes involved in the diversification of secondary metabolites. Comparative transcriptome analysis of A. carmichaelii with A. heterophyllum identified 20,232 orthogroups, representing 30,633 unigenes of A. carmichaelii, gene ontology enrichment analysis of which revealed essential biological process together with a secondary metabolic process to be highly enriched. Unigenes identified in this study are strong candidates for aconitine-type diterpene alkaloid biosynthesis, and will serve as useful resources for further validation studies.

The intricate interplay between viruses and hosts involves microRNAs (miRNAs) to regulate gene expression by targeting cellular/viral messenger RNAs (mRNAs). Mouse mammary tumour virus (MMTV), the aetiological agent of breast cancer and leukaemia/lymphomas in mice, provides an ideal model to explore how viral and host miRNAs interact to modulate virus replication and tumorigenesis. We previously reported dysregulation of host miRNAs in MMTV-infected mammary glands and MMTV-induced tumours, suggesting a direct interaction between MMTV and miRNAs. To explore this further, we systematically examined all potential interactions between host miRNAs and the MMTV genome using advanced prediction tools. Leveraging miRNA sequencing data from MMTV-expressing cells, we identified dysregulated miRNAs capable of targeting MMTV. Docking analysis validated the interaction of three dysregulated miRNAs with the MMTV genome, followed by confirmation with RNA immunoprecipitation assays. We further identified host targets of these miRNAs using mRNA sequencing data from MMTV-expressing cells. These findings should enhance our understanding of how MMTV replicates and interacts with the host to induce cancer in mice, a model important for cancer research. Given MMTV’s potential zoonosis and association with human breast cancer/lymphomas, if confirmed, our work could further lead to novel miRNA-based antivirals/therapeutics to prevent possible MMTV transmission and associated cancers in humans.

Enzymes are key proteins performing the basic functional activities in cells. In humans, enzymes can be also responsible for diseases, and the molecular mechanisms underlying the genotype to phenotype relationship are under investigation for diagnosis and medical care. Here, we focus on highlighting enzymes that are active in different metabolic pathways and become relevant hubs in protein interaction networks. We perform a statistics to derive our present knowledge on human metabolic pathways (the Kyoto Encyclopaedia of Genes and Genomes (KEGG)), and we found that activity aldehyde dehydrogenase (NAD(+)), described by Enzyme Commission number EC 1.2.1.3, and activity acetyl-CoA C-acetyltransferase (EC 2.3.1.9) are the ones most frequently involved. By associating functional activities (EC numbers) to enzyme proteins, we found the proteins most frequently involved in metabolic pathways. With our analysis, we found that these proteins are endowed with the highest numbers of interaction partners when compared to all the enzymes in the pathways and with the highest numbers of predicted interaction sites. As specific enzyme protein test cases, we focus on Alpha-Aminoadipic Semialdehyde Dehydrogenase (ALDH7A1, EC 2.3.1.9) and Acetyl-CoA acetyltransferase, cytosolic and mitochondrial (gene products of ACAT2 and ACAT1, respectively; EC 2.3.1.9). With computational approaches we show that it is possible, by starting from the enzyme structure, to highlight clues of their multiple roles in different pathways and of putative mechanisms promoting the association of genes to disease.

To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the micro RNA（mi RNA） expression profile in rat cortex after focal cerebral ischemia/reperfusion injury using mi RNA microarrays and bioinformatic tools to systematically analyze Gene Ontology（GO） function classifications, as well as the signaling pathways of genes targeted by these differentially expressed mi RNAs. Our results show significantly changed mi RNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 mi RNAs up-regulated and 44 mi RNAs down-regulated. Target genes of these differentially expressed mi RNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a mi RNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that mi RNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding mi RNA expression and function may shed light on the molecular mechanism of cerebral ischemia/reperfusion injury.

Background Due to the cave oligotrophic environment, this habitat presents a challenge for microorganisms to colonize and thrive. However, it has been well documented that microorganisms play important roles in cave development. Survival of microbes in this unique habitat likely involves a broad range of adaptive capabilities. Recently, cave microbiomes all over the world are of great scientific interest. However, the majority of investigations focused mostly on small subunit ribosomal RNA (16S rRNA) gene, leaving the ecological role of the microbial community largely unknown. Here, we are particularly interested in exploring the taxonomic composition and metabolic potential of microorganisms in soil from Manao-Pee cave, a subterranean limestone cave in the western part of Thailand, by using high-throughput shotgun metagenomic sequencing. Results From taxonomic composition analysis using ribosomal RNA genes (rRNA), the results confirmed that Actinobacteria (51.2%) and Gammaproteobacteria (24.4%) were the dominant bacterial groups in the cave soil community. Metabolic potential analysis, based on six functional modules of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, revealed that functional genes involved in microbial metabolisms are highly represented in this community (40.6%). To better understand how microbes thrive under unfavorable cave condition, we focused on microbial energy metabolism. The results showed that microbial genes involved in oxidative phosphorylation were the most dominant (28.8%) in Manao-Pee cave, and were followed by methane metabolism (20.5%), carbon fixation (16.0%), nitrogen metabolism (14.7%), and sulfur metabolism (6.3%). In addition, microbial genes involved in xenobiotic biodegradation (26 pathways) and in production of secondary metabolites (27 pathways) were also identified. Conclusion In addition to providing information on microbial diversity, we also gained insights into microbial adaptations and survival strategies under cave conditions. Based on rRNA genes, the results revealed that bacteria belonging to the Actinobacteria and Gammaproteobacteria were the most abundant in this community. From metabolic potential analysis, energy and nutrient sources that sustain diverse microbial population in this community might be atmospheric gases (methane, carbon dioxide, nitrogen), inorganic sulfur, and xenobiotic compounds. In addition, the presence of biosynthetic pathways of secondary metabolites suggested that they might play important ecological roles in the cave microbiome.

[This corrects the article DOI: 10.3389/fpls.2025.1543380.].

High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg—33% (20/60) and wild-type (WT)—7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.

Background Rice plants show yellowing, stunting, withering, reduced tillering and utimately low productivity in susceptible varieties under low temperature stress. Comparative transcriptome analysis was performed to identify novel transcripts, gain new insights into different gene expression and pathways involved in cold tolerance in rice. Results Comparative transcriptome analyses of 5 treatments based on chilling stress exposure revealed more down regulated genes in susceptible and higher up regulated genes in tolerant genotypes. A total of 13930 and 10599 differentially expressed genes (DEGs) were detected in cold susceptible variety (CSV) and cold tolerant variety (CTV), respectively. A continuous increase in DEGs at 6, 12, 24 and 48 h exposure of cold stress was detected in both the genotypes. Gene ontology (GO) analysis revealed 18 CSV and 28 CTV term significantly involved in molecular function, cellular component and biological process. GO classification showed a significant role of transcription regulation, oxygen, lipid binding, catalytic and hydrolase activity for tolerance response. Absence of photosynthesis related genes, storage products like starch and synthesis of other classes of molecules like fatty acids and terpenes during the stress were noticed in susceptible genotype. However, biological regulations, generation of precursor metabolites, signal transduction, photosynthesis, regulation of cellular process, energy and carbohydrate metabolism were seen in tolerant genotype during the stress. KEGG pathway annotation revealed more number of genes regulating different pathways resulting in more tolerant. During early response phase, 24 and 11 DEGs were enriched in CTV and CSV, respectively in energy metabolism pathways. Among the 1583 DEG transcription factors (TF) genes, 69 WRKY, 46 bZIP, 41 NAC, 40 ERF, 31/14 MYB/MYB-related, 22 bHLH, 17 Nin-like 7 HSF and 4C3H were involved during early response phase. Late response phase showed 30 bHLH, 65 NAC, 30 ERF, 26/20 MYB/MYB-related, 11 C3H, 12 HSF, 86 Nin-like, 41 AP2/ERF, 55 bZIP and 98 WRKY members TF genes. The recovery phase included 18 bHLH, 50 NAC, 31 ERF, 24/13 MYB/MYB-related, 4 C3H, 4 HSF, 14 Nin-like, 31 bZIP and 114 WRKY TF genes. Conclusions Transcriptome analysis of contrasting genotypes for cold tolerance detected the genes, pathways and transcription factors involved in the stress tolerance.

This study investigates the adaptive mechanisms that enable a single wild barley (Hordeum spontaneum) accession to withstand extreme salinity. Salt stress reshapes plant metabolism and gene expression, offering targets for breeding salt-tolerant cereals. A time-course RNA-Seq experiment was conducted on leaves exposed to 500 mM NaCl, followed by differential expression and functional annotations to characterize transcriptomic responses. Transcriptomic profiling identified 140 dynamically upregulated genes distributed across 19 interconnected metabolic pathways, with phased activation of oxidative phosphorylation, nitrogen assimilation, lipid remodeling, and glutathione metabolism. Central metabolic nodes, including acetyl-CoA, hexadecanoyl-CoA, and ubiquinone, coordinated bioenergetic output, membrane stabilization, and redox homeostasis. Ribose-5-phosphate and ribulose-5-phosphate linked glycolysis and the pentose phosphate pathway, supplying NADPH for antioxidant defense and nucleotide repair, while riboflavin derived from Ru5P enhanced flavoprotein activity. In parallel, glucose and fructose-6-phosphate supported osmotic adjustment and glycolytic flux, and increased sterol and cuticular lipid biosynthesis, including cholesterol-like compounds, reinforced membrane integrity and calcium signaling. Glutathione and N-acetyl-glutamate together mitigated oxidative stress and modulated polyamine metabolism, strengthening cellular resilience under salt stress. These findings outline a coordinated network of metabolic and redox pathways that can guide the engineering of salt-tolerant cereals for sustainable production in saline agroecosystems.

Background Bacteria present in cave often survive by modifying their metabolic pathway or other mechanism. Understanding these adopted bacteria and their survival strategy inside the cave is an important aspect of microbial ecology. Present study focuses on the bacterial community and geochemistry in five caves of Mizoram, Northeast India. The objective of this study was to explore the taxonomic composition and presumed functional diversity of cave sediment metagenomes using paired end Illumina sequencing using V3 region of 16S rRNA gene and bioinformatics pipeline. Results Actinobacteria, Proteobacteria, Verrucomicrobia and Acidobacteria were the major phyla in all the five cave sediment samples. Among the five caves the highest diversity is found in Lamsialpuk with a Shannon index 12.5 and the lowest in Bukpuk (Shannon index 8.22). In addition, imputed metagenomic approach was used to predict the functional role of microbial community in biogeochemical cycling in the cave environments. Functional module showed high representation of genes involved in Amino Acid Metabolism in (20.9%) and Carbohydrate Metabolism (20.4%) in the KEGG pathways. Genes responsible for carbon degradation, carbon fixation, methane metabolism, nitrification, nitrate reduction and ammonia assimilation were also predicted in the present study. Conclusion The cave sediments of the biodiversity hotspot region possessing a oligotrophic environment harbours high phylogenetic diversity dominated by Actinobacteria and Proteobacteria. Among the geochemical factors, ferric oxide was correlated with increased microbial diversity. In-silico analysis detected genes involved in carbon, nitrogen, methane metabolism and complex metabolic pathways responsible for the survival of the bacterial community in nutrient limited cave environments. Present study with Paired end Illumina sequencing along with bioinformatics analysis revealed the essential ecological role of the cave bacterial communities. These results will be useful in documenting the biospeleology of this region and systematic understanding of bacterial communities in natural sediment environments as well.