Abnormal development of the prefrontal cortex (PFC) is associated with a number of neuropsychiatric disorders that have an onset in childhood or adolescence. Although the basic laminar structure of the PFC is established in utero, extensive remodeling continues into adolescence. To map the overall pattern of changes in cortical gene transcripts during post-natal development, we made serial measurements of mRNA levels in mouse PFC using oligonucleotide microarrays. We observed changes in mRNA transcripts consistent with known post-natal morphological and biochemical events. Overall, most transcripts that changed significantly showed a progressive decrease in abundance after birth, with the majority of change between post-natal weeks 2 and 4. Genes with cell proliferative, cytoskeletal, extracellular matrix, plasma membrane lipid / transport, protein folding, and regulatory functions had decreases in mRNA levels. Quantitative PCR verified the microarray results for six selected genes: DNA methyltransferase 3A (Dnmt3a), procollagen, type III, alpha 1 (Col3a1), solute carrier family 16 (monocarboxylic acid transporters), member 1 (Slc16a1), MARCKS-like 1 (Marcksl1), nidogen 1 (Nid1) and 3-hydroxybutyrate dehydrogenase (heart, mitochondrial) (Bdh).
Microarray analysis of the developing cortex.
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View SamplesUterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including del(7)(q22q32). To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t-tests demonstrates this matched design is critical to eliminate confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosacism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis.
Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.
Disease
View SamplesActivation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production.
HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.
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View SamplesThis work is part of the paper: Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model, Rothweiler S et al, Laboratory Investigation, 2014
Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesWe examine the global effect of hBD3 on transcription in TLR4-stimulated macrophages and for the first time show that hBD3 inhibits the transcription of critical pro-inflammatory genes.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesGene expression profiling for identification of genes regulated by DNA methylation
Genome-wide screening of genes regulated by DNA methylation in colon cancer development.
Specimen part, Cell line
View SamplesHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/�-catenin signaling. Microarray analysis identified two tumor subclasses resembling distinct phases of liver development, and a 16-gene signature discriminated invasive and metastatic hepatoblastomas, and predicted prognosis with high accuracy. <br></br>
Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesIn this study we investigated changes in gene expression induced by 2cPE (a non-selective isopeptidase inhibitor) in leukemia cells isolated from 10 different patients suffering of B-cell chronic lymphocytic leukemia. We compared 2cPE induced changes in mRNA levels with those induced by bortezomib, another well characterized proteasome inhibitor. Both inhibitors trigger apoptosis in leukemia cells.
The isopeptidase inhibitor 2cPE triggers proteotoxic stress and ATM activation in chronic lymphocytic leukemia cells.
Specimen part, Subject
View SamplesAnalysis of the effects of sulphatide specific antibody (O4, 20microg/ml) on myelinating cultures generated from dissociated embryonic rat spinal cord after 24 hours treatment to give insights into effects of lipid-specific antibodies and its implication in demyelinating diseases.
Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis.
Specimen part, Treatment
View Samples