Introduction: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH. Methods: Fasting plasma for determination of lipid profiles, inflammatory molecules, and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene expression profile was analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. Results: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared to controls. Atorvastatin treatment modified the expression of 87 genes. Changes in the expression of some genes, confirmed by real time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen tumor necrosis factor receptor superfamily, member 25 and CD96) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. Conclusions: Our results demonstrate clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.
Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.
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View SamplesSequencing of a pool of 9 bulls of varying conception rate (CR) scores from -2.9 to 3.5.
Cryopreserved bovine spermatozoal transcript profile as revealed by high-throughput ribonucleic acid sequencing.
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View SamplesUpstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the non-coding RNA roX plays key roles in the control of X-chromosome dosage compensation in both sexes. In order to investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of non-coding RNAs in a sex-specific fashion. Overall design: Two replicates of UNR IP were performed in D.melanogaster adult males and females, and enrichment in either sex was compared with IgG IP as control. To correlate sex-specific UNR binding with sex-specific transcription and splicing we performed RNA-Seq experiments in males and females.
Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR.
Specimen part, Subject
View SamplesWe have previously observed that expression of HLA genes associate with histology of adrenocortical tumors (PMID 17234769).
Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.
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View SamplesWe have previously observed that expression of HLA genes associate with histology of adrenocortical tumors (PMID 17234769).
Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.
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View SamplesPediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease.
Gene expression profiling of childhood adrenocortical tumors.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated ordination of miRNA and mRNA expression profiles.
Specimen part
View SamplesSeveral studies have shown that negative and positive miRNA-mRNA correlations are symmetrically distributed. While negative correlations are consistent with a faster degradation of miRNA targets, the presence of positive correlations suggests bidirectional interactions between the two classes of molecules. However, a comprehensive study of miRNA and mRNA correlations is lacking. A homogeneous map of miRNA and mRNA relationships was obtained by multidimensional scaling (MDS) applied to a single matrix including both heterologous (miRNA-mRNA) and homologous (miRNA-miRNA and mRNA-mRNA) correlations.
Integrated ordination of miRNA and mRNA expression profiles.
Specimen part
View SamplesThese data can be used for evaluation of the clinical utility of the research-based PAM50 subtype predictor in predicting pathological complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
Research-based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2-positive breast cancer in the NOAH study.
Age, Treatment, Race
View SamplesThe second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by mechanisms that are poorly understood. Here, we assessed a role for mitochondria and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild-type (WT) S49 lymphoma cells and the S49 variant, D- (cAMP-deathless), which lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP-promoted G1 growth arrest. Treatment of WT, but not D-, S49 cells with 8-CPT-cAMP for 24 h induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and Smac and increase in caspase-3 activity. Gene expression analysis (using Affymetrix 430 2.0 Arrays) revealed that WT and D- cells incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP-regulated gene expression at 2h (~800 transcripts) and 6h (~1000 transcripts) (|Fold|>2, P<0.06); by contrast, at 24h ~2500 and ~1100 transcripts were changed in WT and D- cells, respectively. Using an approach that combined regression analysis, clustering and functional annotation to identify transcripts that showed differential expression between WT and D- cells, we found differences in cAMP-mediated regulation of mRNAs involved in transcriptional repression, apoptosis, the cell cycle, RNA splicing, Golgi and lysosomes. The 2 cell lines differed in CREB phosphorylation and expression of the transcriptional inhibitor Icer and in cAMP-regulated expression of genes in the Inhibitor of apoptosis (IAP) and Bcl families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways.
Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial-dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49 lymphoma cells.
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