Addition of CO2 to the inspired gas can ameliorate lung injury during high tidal volume mechanical ventilation in animal models. Although some effects of hypercapnia on physiology and cell signaling have been characterized, we hypothesized that assessment of genome-wide gene expression patterns would reveal novel pathways of protection.
α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury.
Sex, Specimen part
View SamplesSuperior frontal gyrus grey and white matter
Unique transcriptome patterns of the white and grey matter corroborate structural and functional heterogeneity in the human frontal lobe.
No sample metadata fields
View SamplesThe goal of the present study was to compare hepatic toxicogenomic signatures across in vitro and in vivo mouse models following exposure to acetaminophen (APAP) or its relatively nontoxic regioisomer 3'-hydroxyacetanilide (AMAP). Two different Affymetrix microarray platforms and one Agilent Oligonucleotide microarray were utilized. APAP and AMAP treatments resulted in significant and large changes in gene expression that were quite disparate, and likely related to their different toxicologic profiles. Ten transcripts, all of which have been implicated in p53 signaling, were identified as differentially regulated at all time-points following APAP and AMAP treatments across multiple microarray platforms. Protein-level quantification of p53 activity aligned with results from the transcriptomic analysis, thus supporting the implicated mechanism of APAP-induced toxicity. Therefore, the results of this study provide good evidence that APAP-induced p53 phosphorylation and an altered p53-driven transcriptional response are fundamental steps in APAP-induced toxicity.
p53 Contributes to Differentiating Gene Expression Following Exposure to Acetaminophen and Its Less Hepatotoxic Regioisomer Both In Vitro and In Vivo.
Specimen part
View SamplesOligomeric proanthocyanidins (OPCs) reduce triglycerides in the nematode C. elegans. Lipase was strongly inhibited in vitro accompanied by the reduction of total triglyceride storage capacity in vivo; Lipophilic staining was also attenuated in wild type worms and high-fat mutants exposed to OPCs. Apart from biochemical analyses, lipid metabolism was also genetically regulated, emphasizing the necessity to study underlying regulation mechanisms in intact animals. To gain a deeper insight into the potential gene targets of purified oligomeric proanthocyanidin trimer gallate (pOPC7), a binary microarray assay was carried out with wild type N2 populations continuously exposed to a bacterial diet with or without pOPC7.
Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in <i>Caenorhabditis elegans</i>.
Sex, Treatment
View SamplesMethylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimers disease, as well as cancer.
The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.
Sex, Specimen part, Time
View SamplesNormal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER1 breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identi?ed differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissues response to an existing tumor.
Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients.
Specimen part, Disease, Disease stage, Subject
View SamplesGene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile
Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.
Specimen part, Disease, Disease stage
View SamplesWe use RNAseq analysis as an un-biased and highly sensitive measurement of global transcriptomic changes upon the loss of HPX-2. The RNAseq result provided insights into the potential physiological processes HPX-2 is involved in. Overall design: L4 stage worms were exposed to E. faecalis or E. coli for 16 hours and total RNA was extracted for 5 biological replicates. Illumina Hiseq 4000 sequencer with 75 nt pair-ended read format was used to conduct the sequencing.
Heme peroxidase HPX-2 protects Caenorhabditis elegans from pathogens.
Subject
View SamplesThe goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Cell line, Subject
View SamplesTo assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-cat) in which high levels of active -catenin are maintained throughout T cell development. Young R26-cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age.
β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL.
Age, Specimen part
View Samples