Ochratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
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View SamplesThis study aimed at investigating the impact of chronic ingestion of sebacic acid (SA), a 10 carbons medium-chain dicarboxylic acid, on glycemic control in a mouse model of type 2 diabetes (db/db mice). Three groups of 15 mice were fed for 6 weeks either a chow diet (Ctrl), or a chow diet supplemented with 1.5% or 15% (SA1.5% and SA15% resp.) energy from SA. Fasting glycemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results-After 42 days of supplementation, fasting glycemia and HbA1c were ~70% and ~25% lower in the SA15% group compared to other groups showing a beneficial effect of SA on hyperglycemia. During OGTT, blood glucose area under the curve (AUC) was reduced after SA15% compared to other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared to Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusions-Dietary supplementation of SA largely improves glycemic control in a mouse model of type 2 diabetes. This beneficial effect may be due (1) to a reduced hepatic glucose output resulting from transcriptional down regulation of key gluconeogenesis genes and (2) to an improved glucose induced-insulin secretion.
Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.
Specimen part
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
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View SamplesA673 cells were exposed in triplicate to three agrichemicals for 24hrs at 8 concentrations and a DMSO vehicle control (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 M plus DMSO vehicle controls). While a common set of DMSO controls was used, these CEL files were RMA normalized independently with each of the chemical treated groups. Gene expression was measured on an Affymetrix GeneTitan system. The compounds used were fenbuconazole (a.k.a FENB, CAS # 114369-43-6) a triazole fungicide, imazalil (a.k.a. IMAZ, CAS # 35554-44-0), an azole pesticide, and 2,4-dichlorophenoxyacetic acid (a.k.a. 2,4-D or 2-4-D in file names, CAS # 94-75-7), a chlorophenoxy herbicide.
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation.
Specimen part, Cell line
View SamplesMCF7 cells were exposed in triplicate to three agrichemicals for 24hrs at 8 concentrations and a DMSO vehicle control (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 M plus DMSO vehicle controls). While a common set of DMSO controls was used, these CEL files were RMA normalized independently with each of the chemical treated groups. Gene expression was measured on an Affymetrix GeneTitan system. The compounds used were fenbuconazole (a.k.a FENB, CAS # 114369-43-6) a triazole fungicide, imazalil (a.k.a. IMAZ, CAS # 35554-44-0), an azole pesticide, and 2,4-dichlorophenoxyacetic acid (a.k.a. 2,4-D or 2-4-D in file names, CAS # 94-75-7), a chlorophenoxy herbicide.
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation.
Specimen part, Cell line
View SamplesHepaRG cells were exposed in triplicate to three agrichemicals for 24hrs at 8 concentrations and a DMSO vehicle control (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 M plus DMSO vehicle controls). While a common set of DMSO controls was used, these CEL files were RMA normalized independently with each of the chemical treated groups. Gene expression was measured on an Affymetrix GeneTitan system. The compounds used were fenbuconazole (a.k.a FENB, CAS # 114369-43-6) a triazole fungicide, imazalil (a.k.a. IMAZ, CAS # 35554-44-0), an azole pesticide, and 2,4-dichlorophenoxyacetic acid (a.k.a. 2,4-D or 2-4-D in file names, CAS # 94-75-7), a chlorophenoxy herbicide.
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation.
Specimen part, Cell line
View SamplesHpeG2 cells were exposed in triplicate to three agrichemicals for 24hrs at 8 concentrations and a DMSO vehicle control (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 M plus DMSO vehicle controls). While a common set of DMSO controls was used, these CEL files were RMA normalized independently with each of the chemical treated groups. Gene expression was measured on an Affymetrix GeneTitan system. The compounds used were fenbuconazole (a.k.a FENB, CAS # 114369-43-6) a triazole fungicide, imazalil (a.k.a. IMAZ, CAS # 35554-44-0), an azole pesticide, and 2,4-dichlorophenoxyacetic acid (a.k.a. 2,4-D or 2-4-D in file names, CAS # 94-75-7), a chlorophenoxy herbicide.
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation.
Specimen part, Cell line
View SamplesInduction of dnFGFR2bfor 3 partially overlapping intervals at the early stages of otocyst morphogenesis revealed expected and novel up and downregulated genes that were validated by in situ hybridization analysis. Cell cyle genes were enriched in the downregulated datasets and human hearingloss genes were enriched in the upregulated datasets. Overall design: Differential mRNA expression analysis of pooled Rosa26rtTA/+ (control) and pooled Rosa26rtTA/+;Tg(tetO-s(dn)Fgfr2b)/+ (experimental) embryos induced with doxycycline for the indicated intervals. N=4 biological replicates per treatment (i.e. 4 pregnant females)
Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis.
Subject
View SamplesAn increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers.
Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant?
Specimen part, Time
View SamplesWe assessed how lack of ISG15 influences the levels of transcripts after IFNa stimulation.
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation.
Specimen part
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