Project description:RNAseq and LC/MS metabolomics analysis of C. difficile strain 630 grown in BHIS media with 50% (vol/vol) faecal water added, compared with control BHIS containing only the additional PBS used for prep of Faecal water. Cells grown in biological triplicates to late log phase (T=6h) prior to harvest. Goal was to determine changes in gene expression caused by exposure to Faecal water, and changes in the metabolite profile of faecal water containing medium when incubated with actively growing C. difficile cells
Project description:mccc-1(ww4) mutant animals has no obvious developmental defect, but we observed different abundance of many metabolites by LC-MS/MS analysis. Then, we assumed different metabolite abundance is associated with different metabolic gene expression, sucha that RNA-seq was performed to examine differently expressed gene.
Project description:The cardioprotective effects of long chain (LC) 3PUFA can be achieved at the gene expression level, notably in liver. However, the complexity of biological pathways modulations and the nature of the bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC 3PUFA on the production of peroxidated metabolites and on global gene expression in liver. The intake of LC ?3PUFA increased, in a dose-dependent manner, their incorporation in liver phospholipids but also the hepatic production of 4-HHE. Pathways related to inflammation were dose-dependently associated with the 3 groups but Group 2 was rather associated with inflammatory effects while Group 3 was anti-inflammatory. LC ?3PUFA had no effect on PPAR-controlled genes. However, they modified, in a dose-dependent manner, the expression of major genes related to lipoprotein metabolism (LDLR, VLDLR, INSIG1 and MTTP), possibly through the FXR signaling pathway. In conclusion, the effect of LC ?3PUFA is dependent on the dose possibly because of the production of peroxidated metabolites such as 4-HHE. New-Zealand white rabbits were fed (7 wk) a high cholesterol diet and received by daily oral gavages either oleic acid rich oil or a mixture of oils providing 0.1% (Group 1), 0.5% (Group 2) or 1% (Group 3) of energy as docosahexaenoic acid. Specific peroxidated metabolite issued from LC 3PUFA (4-hydroxyhexenal or 4-HHE) were measured by GC/MS/MS and transcription profiling was conducted in liver. Differentially expressed genes were identified using Bioconductor (Moderated p<0.05, Fold Change>1.20) and clustered into pathways (Ingenuity Pathway Analysis 7.0).
Project description:Accurate DNA replication is essential for genome integrity, with dysregulated replication dynamics, replication stress and genomic instability-hallmarks of cancer and aging. Here, we identify NAT10-mediated β-hydroxybutyrylation (Kbhb) of histones that safeguards replication fork progression, alleviates replication stress, and preserves genomic stability. DNA fiber analyses show β-hydroxybutyrate (BHB) treatment enhances replication efficiency while maintaining fork symmetry, effects abolished by NAT10 depletion or inhibition. BrdU/EdU labeling, FACS analyses reveal that NAT10-mediated Kbhb accelerates replication fork velocity and shortens S-phase duration. LC-MS/MS profiling shows no significant changes in origin firing following BHB treatment. Mechanistically, NAT10-mediated Kbhb modulates chromatin association, thereby modulating chromatin accessibility to establish a replication-permissive environment. This epigenetic remodeling mitigates replication stress markers and genomic instability. Conserved effects in transformed and primary cell models position NAT10 as a metabolic-epigenetic nexus linking nutrient signaling to replication fidelity. Our findings suggest targeting Kbhb signaling as a potential therapeutic strategy against replication stress-associated pathologies.
Project description:Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing and LC/MS. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation. LC/MS indicated that most of amino acids and ADP decreased in VB1 processed culture. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro. This study will be benefit for our deeply understanding for impact of VB1 to M.tuberculosis.
Project description:Tropical scleractinian corals are particularly vulnerable to global warming as elevated sea surface temperatures (SSTs) disrupt the delicate balance between the coral host and their algal endosymbionts, leading to symbiont expulsion, mass bleaching and mortality. While satellite sensing of SST has proved a reliable predictor of coral bleaching at the regional scale, there are large deviations in bleaching severity and mortality on the local scale that are poorly understood. Here, we show that internal waves play a major role in explaining local coral bleaching and mortality patterns in the Andaman Sea. Despite a severe region-wide SST anomaly in May 2010, frequent upslope intrusions of cold sub-pycnocline waters due to breaking large-amplitude internal waves (LAIW) mitigated coral bleaching and mortality in shallow waters. In LAIW-sheltered waters, by contrast, bleaching-susceptible species suffered severe bleaching and total mortality. These findings suggest that LAIW benefit coral reefs during thermal stress and provide local refugia for bleaching-susceptible corals. LAIW are ubiquitous in tropical stratified waters and their swash zones may thus be important conservation areas for the maintenance of coral diversity in a warming climate. Taking LAIW into account can significantly improve coral bleaching predictions and provide a valuable tool for coral reef conservation and management.
Project description:We studied the lipidome (236 individual lipid species including sphingolipids, ceramides, cholesterol, gangliosides, phosphatidylethanolamines) in basal and LPS-stimulated human monocyte derived macrophages (MDMs) over a time-course by LC-MS (30min, 3h, 8h, 16h; n=12 human donors). In order to explore how transcriptomic changes induced by LPS stimulation can correlate with changes in the lipidome, we performed RNAsequencing on MDMs from 4 donors over a time-course (30min, 3h, 8h, 16h)