Project description:The phosphorylomics data of liver tissue of 16-week-old HFHC-induced mice treated with saline or breviscapine for 8 weeks. The mice fed with high fat and high cholesterol were also divided into two groups. The control group was treated with normal saline for 8W, and the drug group was treated with breviscapine for 8W n=3.
Project description:Provided later Pregnant Fisher 344 rats will be purchased from Charles River Laboratories, Inc. and delivered to CIIT on gestational day (GD) 7 (GD0 = day first vaginal plug positive). At gestational day 12 (GD12), the dams will be exposed once/day until GD20 to 50 mg/kg dibutyl phthalate (DBP) in corn oil vehicle via oral gavage. Each dose group will contain 4-6 vehicle control or phthalate treated dams. Groups of animals will be sacrificed at GD20, postnatal day (PND) 35, and PND90 for endpoint analysis. At GD20, treated and control animals will be examined for various endpoints including body weight, testicular histopathology, gene expression profile via microarray analysis, and anogenital distance (AGD). AGD (at parturition; PND1) and nipple number/location (at PND14 and day of sacrifice) will be determined on animals in the postnatal groups. At PND35 or 90, one male from each in utero corn oil vehicle or DBP exposed group will receive a second gavage of either corn oil or 500 mg/kg DBP. 6 hours after the second gavage, the following endpoints will be examined: 1) testis histopathology; 2) spermatid head quantification (PND90 only); 3) testis and body weights; 5) genome-wide gene expression (via microarray); and 6) germ cell apoptosis (TUNEL assay).
Project description:Benzo[a]pyrene (BaP) is a very extensively studied prototypical polycyclic aromatic hydrocarbons (PAHs). Previous work in our laboratory showed no changes of microRNA (miRNA) expression in liver following a 3 days exposure to BaP, suggesting a lack of miRNA transcriptional responses to aryl hydrocarbon receptor agonists and/or DNA damage. Here, we studied 25-week old male MutaTM Mouse exposed to 25, 50, and 75 mg/kg/day BaP by oral gavage for 28 consecutive days. MAANOVA identified 110 differentially expressed genes (adjusted p < 0.05) with fold change greater than 1.5. The genes most affected included those involved in xenobiotic metabolism, phase II metabolizing enzymes, as well as the downstream targets of p53. Pathway specific RT-PCR was used to confirm the p53 response. A single significant increase in miRNA expression was identified (mir-34a and validated using the Qiagen miScript PCR system). This miRNA is known to be transcriptionally activated by p53. Ingestion of BaP leads to widespread changes in gene expression in mouse liver, with enrichment of genes involved in cell cycle arrest, DNA damage response, and apoptosis via the p53 pathway. In contrast, miRNA expression was relatively unaffected. Only miR-34a was significantly up-regulated, and may therefore play a critical role in the post-transcriptional regulation of p53 and/or its downstream targets. Keywords: Agilent mouse 8 x 15K miRNA microarray system with miRNA complete labeling and hyb kit were used to assess miRNA expression in response to 25, 50, and 75 mg/kg BaP treatment RNA samples from 3 control and 5 mice per treatment group (24mg/kg, 50mg/kg, and 75mg/kg) containing 100 ng were labelled using Agilent?s miRNA complete labelling and Hyb Kit (Agilent Tech, Mississauga, ON, Canada).
Project description:Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Experiment Overall Design: In total 60 samples were analyzed in the present study: vehicle control (n = 12), 1 mg/kg permethrin (n=8), 10 mg/kg permethrin (n = 8), 100 mg/kg permethrin (n = 8), 0.3 mg/kg deltamethrin (n = 8), 1 mg/kg deltamethrin (n = 8), 3 mg/kg deltamethrin (n = 8). Transcriptional profiles for each test subject were obtained independently, without sample pooling. Experiment Overall Design: The publication will include an Appendix Table comparing the variability of RMA values (see Sample VALUE columns) to that of GCOS values (see Sample .CHP files).
Project description:We used RNA-seq to compare the expression profiles of mouse prostate tumors originated from epithelial basal cells to those originated from luminal cells. We next generated expression signatures for both basal and luminal origin tumors by comparison of tumor samples to their respective controls. By comparing luminal to basal signatures we identified a prognostic molecular signature for prostate cancer patient survival. Pten was deleted in prostate basal or luminal cells to induce tumor formation and tumor expression profiles were analyzed by RNA-seq.
Project description: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. Two groups (25 females/group) received oral daily dosing for 7 days of either Vehicle or compound C1 dosed at 100 mg/kg. Five animals from each group were euthanized on Days 1 (4-5 hrs post first dose; received 1 dose), 2 (received 1 dose), 3 (received 2 doses), 5 (received 4 doses) and 8 (received 7 doses). Bladder tissues were collected and profiled at all five time points. Stomach tissues were collected and profiled at the earliest two time points. A single day 3 animal was not available for genomic profiling; therefore, expression data was collected for a total of 49 bladder and 20 stomach samples.
Project description:Proteome profiling was performed to investigate changes at a molecular level in the mouse corneal endothelium (CE) along with the basement membrane exposed to cigarette smoke (CS). Pregnant mice (gestation days 18-20) were placed in a whole-body exposure smoking chamber and a few days later pups were born. After 3½ months of CS exposure, the Confoscan4 scanning microscope was used to examine the CE of CS-exposed and control (Ct) mice. The CE was peeled under a microscope and maintained as four biological replicates (two male and two female) for CS-exposed and Ct mice; each replicate consisted of 16 CE. The proteome of the CE was investigated through mass-spectrometry using 8-plex isobaric tandem mass tags (TMT). The CE images of CS-exposed and Ct mice revealed a difference in the shape of corneal endothelial cells (CECs) accompanied by a nearly 10% decrease in CEC density (p = 3.0e-0.5) resulting from exposure to CS. The proteome profiling identified a total of 524 proteins exhibiting statistically significant changes in CE from CS-exposed and Ct mice. Importantly, proteins known to be an integral part of the basement membrane including COL4α1, COL4α2, COL4α3, COL4α4, COL4α5, and COL4α6, Col8α1, Col8α2, FN1, etc. exhibited diminished protein levels in the CE of CS-exposed mice. Here, we report the effects of CS on the CE, and our data strongly suggest that CS exposure results in reduced CEC density and diminished concentration of proteins known to be an integral part of the basement membrane.
Project description:Following neural tube closure at around E9.5, the rhombic lip within the rhombomere 1/isthmus region ("upper rhombic lip") produces a sequence of neuronal lineages that populate the brainstem and cerebellum. The transcription factor Atoh1 (Math1) is required for this specialized neurogenesis, although the genetic programs that delineate the temporal cell fate changes downstream of Atoh1 are not well characterized. We examined the gene expresion changes that take place within Atoh1 lineages We purified early (E10.5) and late (E13.5) born Atoh1 expressing cells from E14.5 embryos using a transgenic labeling strategy, and analyzed differences in gene expression across the two populations using the microarray data shown below.
Project description:Kidney transplantation remains the optimal therapeutical option for end stage kidney disease. Current immunosuppressive regimens are efficient in combating acute kidney rejection. However, the insight in chronic kidney allograft injury remains limited. Simultaneously, pregnancy in kidney recipients appears more prevalent than during dialysis treatment. Due to ethical issues comprehensive studies on the impact of current immunosuppressive regimens on pregnancy are challenging. Omics- technology enables the systemic insight into biology both of immunity and pregnancy beyond up-to-date collected knowledge. The aim of the study was to investigate the proteomic status of lymphocytes obtained from pregnant female rats under immunosuppressive treatment. The group of 10 pregnant Wistar rat females, 5 of which treated with tacrolimus, mofetil mycophenolate and glicocorticosteroids, 5 used as control. The lymphocytes were obtained and analyzed with mass-spectrometry. The outcomes were verified statistically in terms of proteins up- and down regulation.