Seven novel and potent Raf small molecule kinase inhibitors were evaluated in 7-day oral repeat-dose rat toxicity studies. All compounds tested induced hyperplasia in multiple tissues. Microarrays were used to investigate transciptional changes associated by treatment with a single compound to gain insight into the cellular changes that may contribute to the tissue hyperplasia.
Raf inhibition causes extensive multiple tissue hyperplasia and urinary bladder neoplasia in the rat.
Sex, Specimen part, Treatment
View SamplesMicrovesicles (MV) are small membrane-bound particles comprised of exosomes and various sized extracellular vesicles. These are released by a number of cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation. Microvesicles contain proteins and nucleic acids. Previously, we showed that plasma microvesicles contain microRNAs (miRNAs). Based on our previous report, the majority of peripheral blood microvesicles are derived from platelets while mononuclear phagocytes, including macrophages, are the second most abundant population. Here, we characterized macrophage-derived microvesicles and whether they influenced the differentiation of nave monocytes. We also identified the miRNA content of the macrophage-derived microvesicles. We found that RNA molecules contained in the macrophage-derived microvesicles were transported to target cells, including monocytes, endothelial cells, epithelial cells and fibroblasts. Furthermore, we found that miR-223 was transported to target cells and was functionally active. Based on our observations, we hypothesize that microvesicles bind to and activate target cells. Furthermore, we find that microvesicles induce the differentiation of macrophages. Thus, defining key components of this response may identify novel targets to regulate host defense and inflammation.
Macrophage microvesicles induce macrophage differentiation and miR-223 transfer.
Specimen part, Treatment
View SamplesPurpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome.
Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max.
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View SamplesAerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome.
Aerobic capacity-dependent differences in cardiac gene expression.
Sex
View SamplesA split-split-plot design with 144 experimental units (3 replications x 4 genotypes x 6 time points x 2 treatment types) was used to profile barley plants containing variants of Mla1 and Mla6 powdery mildew resistance genes in response to inoculation with the Blumeria graminis f. sp. hordei (Bgh) isolates 5874 (AvrMla1, AvrMla6). Barley leaves were harvested from inoculated and non-inoculated plants at 6 time points (0,8,16,20,24 and 32 hrs) after Bgh inoculation. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Rico Caldo. The equivalent experiment is BB10 at PLEXdb.]
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Specimen part, Time
View SamplesA large-scale parallel expression analysis was conducted to elucidate Mla-specified responses to powdery mildew infection using 22K Barley1 GeneChip probe arrays. Our goal was to identify genes differentially expressed in incompatible (resistant) vs. compatible (susceptible) and Mla-specified Rar1-dependent vs. -independent interactions. A split-split-plot design with 108 experimental units (3 replications x 2 isolates x 3 genotypes x 6 time points) was used to profile near-isogenic lines containing the Mla1, Mla6, and Mla13 resistance specificities in response to inoculation with the Blumeria graminis f. sp. hordei (Bgh) isolates 5874 (AvrMla1, AvrMla6) and K1 (AvrMla1, AvrMla13). ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Rico Caldo. The equivalent experiment is BB4 at PLEXdb.]
Interaction-dependent gene expression in Mla-specified response to barley powdery mildew.
Specimen part, Time
View SamplesTime-course expression profiles of Bgh challenged barley cultivar C.I. 16151 (harboring the Mla6 powdery mildew resistance allele) and its fast-neutron-derived "Bgh-induced tip cell death1" mutant, bcd1, were compared using the 22K Barley1 GeneChip. Planting, stage of seedlings, harvesting, and experimental design were part of a larger experiment described by Caldo et al. (2004). PLEXdb BB4. Experiment Design: C.I. 16151 (wildtype) and bcd1 (mutant) were planted in separate 20 x 30-cm flats using sterilized potting soil. Each experimental flat consisted of six rows of 15 seedlings, with rows randomly assigned to one of six harvest time points (0, 8, 16, 20, 24, and 32 hai). Seedlings grown to the 1st leaf stage with 2nd leaf unfolded were inoculated with a high density of fresh conidiospores (84 +/- 19 spores/mm2). Groups of flats were placed at 18C (8-hour darkness, 16-hour light) in separate controlled growth chambers corresponding to the Bgh isolates. Rows of plants were harvested at each assigned time points and snap frozen in liquid nitrogen. The entire experiment was repeated three times in a standard split-split-plot design with 72 experimental units (2 genotypes x 2 pathogen isolates x 6 time points x 3 replications). Treatment Description: The samples constituted pairwise combinations of the the cultivar C.I. 16151(containing the Mla6 resistance allele), and its fast-neutron-derived "Bgh-induced tip cell death1" mutant, bcd1 with the two Bgh (Blumeria graminis f. sp. hordei) isolates, 5874 (AvrMla6, AvrMla1) and K1 (AvrMla13, AvrMla1). For each replication, individual genotypes were planted in separate 20 x 30 cm flats using sterilized potting soil. Each experimental flat consisted of six rows of 15 seedlings, with rows randomly assigned to one of six harvest times (0, 8, 16, 20, 24, and 32 hai). Seedlings were grown to the 2nd-leaf stage with 1st leaf unfolded, and inoculation was performed at 4 PM Central Standard Time by tipping the flats at 45oC and dusting the plants with a high density of fresh conidiospores [84 +/- 19 spores/mm2]. This procedure was repeated from the opposite angle to ensure that a high proportion of the cells are in contact with the fungus. This conidial density per unit leaf area routinely results in greater than 50% of epidermal cells that are successfully infected. Groups of flats were placed at 18oC (8 hours darkness, 16 hours light, 8 hours darkness) in separate controlled growth chambers corresponding to the Bgh isolate. Rows of plants were harvested at their assigned harvest times and flash-frozen in liquid nitrogen. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Roger P Wise. The equivalent experiment is BB46 at PLEXdb.]
Interaction-dependent gene expression in Mla-specified response to barley powdery mildew.
Age, Specimen part, Time
View SamplesBarley stripe mosaic virus-induced gene silencing (BSMV-VIGS) was used to identify significant new genes in the regulation of host innate immunity. This experiment was designed to uncover significant changes in Bln1 (Contig12219_at)-silenced plants relative to empty vector and buffer treated controls. Five independent biological replications of a split-plot experimental design were conducted with replications as blocks, treatment with Blumeria graminis f. sp. hordei (Bgh) as the whole-plot factor, and all combinations of genotype (Mla13 and Mla9) and VIGS treatment [Buffer control (mock), BSMV:00 (empty vector), and BSMV:Bln1248] as the split-plot factor for a total of 60 GeneChip hybridizations. Ten seedlings were used as a split-plot experimental unit for each combination of replication, Bgh treatment, genotype, and VIGS treatment. Plants were grown in a controlled 20C glasshouse prior to VIGS treatment. Twelve days after VIGS treatment, half of the plants in each replication were challenged with the compatible Bgh isolate 5874. Top halves of 5 of the 10 seedling third leaves (about 10 cm) from each split-plot experimental unit were harvested into liquid N2 at 32 hours after inoculation (HAI) - the timepoint with the highest differential Bln1 transcript accumulation (Meng et al. 2009), and after initial establishment of the perihaustorial interface (Caldo et al. 2004). The remaining 5 leaves were used to record infection phenotype 7 days later. RNA was isolated for GeneChip hybridization from the 32-HAI samples. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Yan Meng. The equivalent experiment is BB101 at PLEXdb.]
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Age, Specimen part
View SamplesMethylene diphenyl diisocyanate is a chemical known to cause asthma. The present study uses mice to investigate exposure-induced changes in lung gene expression and effects of a chloride channel inhibitor
Analysis of Lung Gene Expression Reveals a Role for Cl<sup>-</sup> Channels in Diisocyanate-induced Airway Eosinophilia in a Mouse Model of Asthma Pathology.
Sex
View SamplesA parallel expression profiling of wild-type and loss-of-function mutants of Mla6 and Mla1 powdery mildew resistance alleles was conducted using Barley1 GeneChip. Barley plants were inoculated with powdery mildew isolate 5874 and first leaves were harvested at 6 time points after pathogen inoculation. This experiment was conducted in split-split-plot experimental design with 3 replications.
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Age, Specimen part, Time
View Samples