7352ea9f-088d-4bbb-9d5c-a3b4fe2eb28f - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001009089 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The in silico single gene deletion step was adapted to simulate the knock-out of all targets of a drug on an objective function such as growth or energy balance. Based on publicly available and in-house large scale transcriptomic data, metabolic models for melanoma were reconstructed, enabling the prediction of 28 candidate drugs and estimating their respective efficacy.
| EGAS00001006463 | EGA
Project description:Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. We utilized gene expression microarrays to examine the transcriptional activity of p53 targets in TOV112D cells after treatment with NSC319726. Triplicate cultures of TOV112D cells untreated, treated with NSC319726. Total RNA was extracted and hybridized to Affymetrix human U133 plus 2.0 microarrays.
2012-02-22 | E-GEOD-35972 | biostudies-arrayexpress
Project description:We aimed to investigate the human skeletal muscle (SkM) DNA methylome after exercise in low carbohydrate (CHO) energy balance (with high fat) compared with exercise in low-CHO energy deficit (with low fat) conditions. The objective to identify novel epigenetically regulated genes and pathways associated with ‘train-low sleep-low’ paradigms. The sleep-low conditions included 9 males that cycled to deplete muscle glycogen while reaching a set energy expenditure. Post-exercise, low-CHO meals (protein-matched) completely replaced (using high-fat) or only partially replaced (low-fat) the energy expended. The following morning resting baseline biopsies were taken and the participants then undertook 75 minutes of cycling exercise, with skeletal muscle biopsies collected 30 minutes and 3.5 hours post exercise. Discovery of genome-wide DNA methylation was undertaken using Illumina EPIC arrays and targeted gene expression analysis was conducted by RT-qPCR. At baseline participants under energy balance (high fat) demonstrated a predominantly hypermethylated (60%) profile across the genome compared to energy deficit-low fat conditions. However, post exercise performed in energy balance (with high fat) elicited a more prominent hypomethylation signature 30 minutes post-exercise in gene regulatory regions important for transcription (CpG islands within promoter regions) compared with exercise in energy deficit (with low fat) conditions. Such hypomethylation was enriched within pathways related to: IL6-JAK-STAT signalling, metabolic processes, p53 / cell cycle and oxidative / fatty acid metabolism. Hypomethylation within the promoter regions of genes: HDAC2, MECR, IGF2 and c13orf16 were associated with significant increases in gene expression in the post-exercise period in energy balance compared with energy deficit. Furthermore, histone deacetylase, HDAC11 was oppositely regulated at the gene expression level compared with HDAC2, where HDAC11 was hypomethylated yet increased in energy deficit compared with energy balance conditions. Overall, we identify some novel epigenetically regulated genes associated with train-low sleep-low paradigms.
2023-03-29 | GSE223786 | GEO
Project description:This article contains raw and processed data related to research published by Swartz et al. [1]. Proteomics data from liver of postpartum dairy cows were obtained by liquid chromatography-mass spectrometry following protein extraction. Differential abundance between liver of cows experiencing either negative energy balance (NEB, n=6) or positive energy balance (PEB, n=4) at 17±3 DIM was quantified using MS1 intensity based label-free. There is a paucity of studies examining the associations of NEB with the liver proteome in early lactation dairy cows. Therefore, our objective was to characterize the differences in the liver proteome in periparturient dairy cows experiencing naturally occurring NEB compared to cows in PEB. In this study, multiparous Holstein dairy cows were milked either 2 or 3 times daily for the first 30 days in milk (DIM) to alter energy balance, and were classified retrospectively as NEB (n=18) or PEB (n=22). Liver biopsies were collected from 10 cows (n=5 from each milking frequency), that were retrospectively classified according to their energy balance (NEB, n=6; PEB, n=4). The liver proteome was characterized using label-free quantitative shotgun proteomics. This novel dataset contains 2,741 proteins were identified, and 68 of those were differentially abundant between NEB and PEB (P≤0.05 and FC±1.5); these findings are discussed in our recent research article [1]. The present dataset of liver proteome can be used as either biological markers for disease or therapeutic targets to improve metabolic adaptations to lactation in postpartum dairy cattle.
2021-10-13 | PXD028124 | Pride
Project description:Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. We utilized gene expression microarrays to examine the transcriptional activity of p53 targets in TOV112D cells after treatment with NSC319726.
2012-02-22 | GSE35972 | GEO
Project description:Serotonin is a monoamine that regulates processes such as energy balance and immune function. Manipulating this pathway in growing dairy calves could promote growth and development by modulating functions and signaling pathways within key organs. In this study, we characterized the adipose and muscle transcriptome of pre-weaned calves with increased serotonin bioavailability through the elucidation of differentially expressed genes.
2020-06-05 | GSE151781 | GEO
Project description:Granulosa cells of dominant follicles originating from dairy cows with severe negative energy balance (BHBH) or mild negative energy balance (BHBL) were compared. Mild negative energy balance (BHBL) is the reference.
2015-07-31 | GSE66116 | GEO
Project description:Granulosa cells of dominant follicles originating from dairy cows with severe negative energy balance (BHBH) or mild negative energy balance (BHBL) were compared. Mild negative energy balance (BHBL) is the reference. Two conditions experiment (BHBH and BHBL); Four pools of 3 biological replicates for each group (total = 12 cows for each group); Two technical replicates per pool (dye-swap).
2015-07-31 | E-GEOD-66116 | biostudies-arrayexpress
Project description:Periparturient cows rely on adipose tissue fatty acid reserves released by lipolysis to offset the negative energy balance induced by physiological changes related to parturition and the onset of lactation. However, lipolysis causes inflammation and structural remodeling in excess predisposes cows to disease. The objective of this study was to determine effects of the periparturient period on the transcriptomic profile of AT using NGS RNAseq
2020-10-09 | GSE159224 | GEO
Project description:RATIONALE: Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets. OBJECTIVE: We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo. METHODS AND RESULTS: Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats. A progressive increase of miR-31 (up to 91.4±11.3 fold) was detected in the infarcted myocardium by quantitative real-time PCR. Following target prediction analysis, reporter gene assays confirmed that miR-31 targets the 3´UTR of cardiac troponin-T (Tnnt2), E2F transcription factor 6 (E2f6), mineralocorticoid receptor (Nr3c2) and metalloproteinase inhibitor 4 (Timp4) mRNAs. In vitro, hypoxia and oxidative stress up-regulated miR-31 and suppressed target genes in cardiac cell cultures, whereas LNA-based oligonucleotide inhibition of miR-31 (miR-31i) reversed its repressive effect on target mRNAs. Therapeutic post-ischemic administration of miR-31i in rats silenced cardiac miR-31 and enhanced expression of target genes, while preserving cardiac structure and function at 2 and 4weeks post-MI. Left ventricular ejection fraction (EF) improved by 10% (from day 2 to 30 post-MI) in miR-31i-treated rats, whereas controls receiving scrambled LNA inhibitor or placebo incurred a 17% deterioration in EF. miR-31i decreased end-diastolic pressure and infarct size; attenuated interstitial fibrosis in the remote myocardium and enhanced cardiac output. CONCLUSION: miR-31 induction after MI is deleterious to cardiac function while its therapeutic inhibition in vivo ameliorates cardiac dysfunction and prevents the development of post-ischemic adverse remodeling.
2017-09-05 | GSE81636 | GEO