Experimental asthma was induced in BALB/c mice by sensitization and challenge with the allergen ovalbumin. Control groups received PBS. To investigate the innate immune component of experimental asthma, we also analyzed recombinase activating gene (RAG) deficient mice following exposure to ovalbumin and control PBS
Hubs in biological interaction networks exhibit low changes in expression in experimental asthma.
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View SamplesThreatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.
Whole blood gene expression profile associated with spontaneous preterm birth in women with threatened preterm labor.
Specimen part
View SamplesRDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur either occupationally or through ordnance that lays unexploded on training ranges. The toxicology of RDX is dominated by acute tonic-clonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Sub-chronic studies have revealed few other toxic effects. The objective of this study was to examine the effect of a single oral dose of RDX on global gene expression in the mammalian brain and liver, using a rodent model.
Global gene expression in rat brain and liver after oral exposure to the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
Specimen part, Cell line
View SamplesObjective: The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDHhigh) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDHhigh cells in ovarian cancer. Methods: We compared ALDHhigh to ALDHlow cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. Results: ALDHhigh cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDHhigh cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following drugable targets were consistently expressed in the ALDHhigh cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18 / FGFR3. Conclusions: Based on functional characterization, ALDHhigh ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified drugable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes.
Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
Specimen part, Cell line
View SamplesHigh temporal resolution RNAseq timecourse of mouse ES differentiation Investigations of transcriptional responses during developmental transitions typically use time courses with intervals that are not commensurate with the timescales of known biological processes. Moreover, such experiments typically focus on protein-coding transcripts, ignoring the important impact of long noncoding RNAs. We evaluated coding and noncoding expression dynamics at unprecedented temporal resolution (6-hourly) in differentiating mouse embryonic stem cells and report the effects of increased temporal resolution on the characterization of the underlying molecular processes. Overall design: Biological duplicate 120 hours of undirected mouse ES cell differentiation sampled 6 hourly Biological duplicate, low passage number (P18) W9.5 ESCs were cultured and differentiated as described previously [PMID:18562676; 17286599]. Cultures were harvested every six hours from the induction of differentiation to 120 hours post differentiation induction. Total RNA from cultures was purified using Trizol (Life Technologies) and DNase treatment was performed by RQ1 DNase (Promega) according to the manufacturer’s instructions. RNA integrity was measured on a Bioanalyzer RNA Nano chip (Agilent). RNA-Seq library preparation and sequencing of Poly-A-NGS libraries generated from 500 ng total RNA using SureSelect Strand Specific RNA Library Preparation Kit (Agilent) according to the manufacturer’s instructions. Paired-end libraries were sequenced to the first 100 bp on a HiSeq 2500 (Illumina) on High Output Mode. Library sequencing quality was determined using FastQC (Babraham Bioinformatics) and FastQ Screen (Babraham Bioinformatics). Illumina adaptor sequence and low quality read trimming (read pair removed if < 20 base pairs) was performed using Trim Galore! (Babraham Bioinformatics: www.bioinformatics.babraham.ac.uk/). Tophat2 [PMID:23618408] was used to align reads to the December 2011 release of the mouse reference genome (mm10) as outlined by Anders et al.[PMID:23975260]. Read counts data corresponding to GENCODE vM2 transcript annotations were generated using HTSeq[PMID:25260700]. All analyses were performed in the R Statistical Environment [PMID:18000755]. Briefly, counts data were background corrected and normalized for library size using edgeR [PMID:19910308], then transformed using voom[PMID:24485249] for differential expression analysis using LIMMA[PMID: 16646809].
High resolution temporal transcriptomics of mouse embryoid body development reveals complex expression dynamics of coding and noncoding loci.
Specimen part, Cell line, Subject, Time
View SamplesT-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the predominant sites of disease in T-ALL and T-LL are observed. To determine if underlying biological distinctions may potentially contribute to some of these differences, we analyzed the global gene expression profiles of malignant T-cell precursors in ten T-ALL and nine T-LL using DNA arrays. Ten additional B-precursor ALL bone marrow samples, were used in a separate analysis.
Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.
No sample metadata fields
View SamplesWe describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. Overall design: mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
No sample metadata fields
View SamplesThis project is based on the hygiene hypothesis that exposure to TB provides a protective mechanism against asthma through specific cytokines and the balance of Th1, Th2 cells. Additionally, expression changes are examined in patients with and without atopy in combination with asthma and PPD status. Expression levels were evaluated in CD4+ cells isolated from peripheral blood of 30 patients. Each patient was evaluated on the entire U133 Affymetrix GeneChip set.
A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.
No sample metadata fields
View SamplesWe performed a factorial experiment examining the effects of calorie restriction (CR) and exercise (EX) in mice. CR mice received 70% of calories but 100% of all other nutrients compared to AL mice. Food consumption, weight gain, and physical activity levels were recorded for 6 weeks.
Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.
No sample metadata fields
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