Human auxiliary liver and combined kidney transplantation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Madeleine Ingelsten
PROVIDER: E-GEOD-8941 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Dietary methionine restriction (MR) has been shown to increase lifespan and decrease adiposity in rodents. This study was designed to examine the transcriptional effects of MR in metabolically relevant tissues. This experiment contains data from the liver. We analyzed MR-induced changes in gene expression using pooled RNA from liver of rats fed either a control purified amino acid diet (DL-methionine content of 0.86%) (CON) or a methionine-restricted diet (DL-methionine content of 0.172%)(MR). Rats were fed Purina rodent diet 5001 until 32 days of age and were then randomly assigned to be fed CON diet or MR diet for 20 months.
2012-04-07 | E-GEOD-28482 | biostudies-arrayexpress
Project description:How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (short-chain acyl-CoA dehydrogenase), encoding the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs), shift consumption away from fat and toward carbohydrate when offered a choice. This finding demonstrated that the loss of a specific enzyme in fatty acid oxidation alters the choice of diet intake. To our knowledge, there are no reports of studies on the effects of dietary fat on the brain transcriptome in genetic models of fatty acid oxidation deficiency. The current study aimed to identify molecular mediators underlying the effects of SCFA oxidation deficiency on food intake. The current study aimed to identify molecular mediators underlying the effects of SCFA oxidation deficiency on food intake. We performed a transcriptional screen for gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either high-fat (HF) or low-fat (LF) diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/- vs. HF Acads+/+ (3917) and Acads+/+ HF vs. LF Acads+/+ (3879) revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that Acads-deficient mice fed HF diet display transcriptional responses that mimic those of wildtype Acads+/+ mice fed LF diet. Intriguingly, genes involved in energy sensing and metabolism followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of several genes in these pathways. Western blotting showed that the combination of Acads deficiency and HF diet increased hypothalamic AMP-kinase, a key protein in an energy-sensing cascade that responds to depletion of ATP. Our results suggest that the decreased beta oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase is the cellular energy-sensing mechanism linking fatty acid oxidation to feeding behavior in this model. Twelve-week old male BALB/cByJ (Acads-/-) and BALB/cByKZ (Acads+/+) mice were fed a high-fat (D12331; Research Diets) and low-fat (D12329) diet for two days. Total RNA from whole brain tissue was obtained from three mutant (Acads-/-) and three wild-type (Acads+/+) mice of each diet group. All mice had similar body weights before diets were initiated. Gene expression in brain was compared between strains and between diets. Twelve-week old male BALB/cByJ (Acads-/-) and BALB/cByKZ (Acads+/+) mice were fed a high-fat (D12331; Research Diets) and low-fat (D12329) diet for two days. Total RNA from liver was obtained from three mutant (Acads-/-) and three wild-type (Acads+/+) mice of each diet group. All mice had similar body weights before diets were initiated. Gene expression in liver was compared between strains and diets.
2012-12-20 | E-GEOD-35180 | biostudies-arrayexpress
Project description:The aim of this study was to identify HDL and apoE-regulated genes in human placental endothelial cells (HPEC), which are exposed to fetal HDL. HPECs extracted from 5 human placentas were cultivated and treated for 16 h with 15ug/ml fetal HDL, 15ug/ml reconstituted HDL (rHDL), or endothelial basal medium (EBM) as vehicle control. Gene expression analysis from these 3 conditions (5 biological replicates) using 15 Applied Biosystems Human Whole Genome Survey V2.0 Microarrays was perfomed and significantly differentially expressed genes between two different groups (HDL vs control or rHDL vs control) were identified.
2011-09-01 | E-MEXP-3299 | biostudies-arrayexpress
Project description:Missense point mutations in the TP53 gene are frequent genetic alterations in human tumor tissue and cell lines derived thereof. Mutant p53 (mutp53) proteins have lost sequence-specific DNA binding, but have retained the ability to interact in a structure-selective manner with non-B DNA and to act as regulators of transcription. To identify functional binding sites of mutp53, we established a small library of genomic sequences bound by p53R273H in U251 human glioblastoma cells using chromatin immunoprecipitation (ChIP). Mutp53 binding to isolated DNA fragments confirmed the specificity of the ChIP. The mutp53 bound DNA sequences are rich in repetitive DNA elements, which are dispersed over non-coding DNA regions. Stable down-regulation of mutp53 expression strongly suggested that mutp53 binding to genomic DNA is functional. We identified the PPARGC1A and FRMD5 genes as p53R273H targets regulated by binding to intronic and intra-genic sequences. We propose a model that attributes the oncogenic functions of mutp53 to its ability to interact with intronic and intergenic non-B DNA sequences and modulate gene transcription via re-organization of chromatin. For the study of the consequences of mutant p53 (R273H) knockdown on gene expression, total RNA from parental U251 glioblastoma cells and UsiA12 clone was prepared from two independent cell culture experiments (biological replicates) and processed for microarray-based profiling of gene expression. UsiA12 clone was derived from the U251 cells transfected with the pSuper-p53 and pCI-neo vectors.
2010-06-24 | E-GEOD-13991 | biostudies-arrayexpress
Project description:The decision of metazoan cells to live or undergo programmed cell death hinges on the balance between the levels of pro- versus anti-apoptotic gene products. The general RNA polymerase II (Pol II) transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 is a co-activator for the pro-apoptotic p53 tumour suppressor protein. Our previous studies identified a specialized isoform of TAF6, termed TAF6 that can specifically be induced in apoptosis. To elucidate the impact of TAF6 on gene expression and cell death, we employed modified antisense oligonucleotides to enforce expression of endogenous TAF6. The induction of endogenous TAF6 triggered apoptosis in several cancer cell lines. Importantly, TAF6 also induces apoptosis in tumor cell lines devoid of p53, placing TAF6 function downstream of p53. Microarray experiments uncovered a TAF6-induced transcriptome landscape displaying enhanced expression of genes of the Notch, oxidative stress, integrin, p53 and apoptosis pathways. Our data show that the TAF6 pathway is a pivotal signalling nexus that controls pro-apoptotic gene expression programs. Keywords: Treatment with splice site switching antisense oligonucleotides, induction of apoptosis Biological triplicates, 3 conditions: control oligonucleotide, Taf6 oligonucleotide, specificity control Bcl-x oligonucleotide
2010-11-27 | E-GEOD-8752 | biostudies-arrayexpress
Project description:Background The complete sequencing of the human genome and its subsequent analysis revealed a predominant role for alternative splicing in the generation of proteome diversity. Splice switching oligonucleotides (SSOs) are a powerful and specific tool to experimentally control alternative splicing of endogenous messenger RNAs in living cells. SSOs also have therapeutic potential to treat diseases that are caused by aberrant splicing. The assignment of biological roles to alternative splicing events of currently unknown function promises to provide a largely untapped source of potential new therapeutic targets. Here we have developed a protocol that combines high sensitivity microarrays with the transfection of SSOs to monitor global changes in gene expression downstream of alternate, endogenous splice events. Findings When applied to a well-characterized splicing event in the Bcl-x gene, the application of high sensitivity microarrays revealed a link between the induction of the Bcl-xS isoform and the repression of genes involved in protein synthesis. Conclusions The strategy introduced herein provides a useful approach to define the biological impact of any given alternative splicing event on global gene expression patterns. Furthermore, our data provide the first link between Bcl-xS expression and the repression of ribosomal protein gene expression. Biological triplicates, 2 conditions: control oligonucleotide, Bcl-x oligonucleotide
2008-10-02 | E-GEOD-9851 | biostudies-arrayexpress
Project description:The Forkhead Box f1 (Foxf1) transcriptional factor (previously known as HFH-8 or Freac-1) is expressed in endothelial and smooth muscle cells in the embryonic and adult lung. To assess effects of Foxf1 during lung injury, we used CCl4 injury model. Foxf1+/- mice developed severe airway obstruction and bronchial edema, associated with increased numbers of pulmonary mast cells and increased mast cell degranulation following injury. Pulmonary inflammation in Foxf1+/- mice was associated with diminished expression of Foxf1, increased mast cell tryptase and increased expression of CXCL12, the latter being essential for mast cell migration and chemotaxis. Foxf1 haploinsufficiency caused pulmonary mastocytosis and enhanced pulmonary inflammation following chemically-induced lung injury, indicating an important role for Foxf1 in the pathogenesis of pulmonary inflammatory responses. Keywords: Influence of genetic modification on the pulmonary inflamation Foxf1+/- mice in which the Foxf1 allele was disrupted by an in-frame insertion of a nuclear localizing -galactosidase (-Gal) gene were bred for ten generations into the Black Swiss mouse genetic background. Carbon tetrachloride (CCl4; Sigma, St Louis, MO) was dissolved in mineral oil at a 1:20 ratio v/v and a single intraperitoneal (i.p.) injection of CCl4 (0.5 l of CCl4/ 1g of body weight) was administered to male Foxf1+/- mice or their wild type (WT) littermates as described.
2008-09-04 | E-GEOD-11112 | biostudies-arrayexpress
Project description:Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 4 mice per group was isolated and differentiated to alternatively activated macrophages with 20 ng/ml M-CSF and 20 ng/ml IL-4 or to iDCs with 20 ng/ml GM-CSF+20 ng/ml IL-4. 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF+IL-4, 2. M-CSF+IL-4+RSG, 3. GM-CSF+IL-4 and 4. GM-CSF+IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 9 days, RNA was isolated and gene expression profiles were analyzed using ABI Mouse Genome Survey Arrays. 4 PPARg +/- LysCre and 4 PPARg fl/- LysCre mice were used to isolate bone marrow and from each alternatively activated macrophages were differentiated with IL-4 and simultaneously treated with vehicle or RSG, iDCs were differentiated with GM-CSF+IL-4 and simultaneously treated with vehicle or RSG. Altogether we analyzed 32 samples with 4 biological replicates as below.
2010-11-18 | E-GEOD-25125 | biostudies-arrayexpress
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.
2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress
Project description:To identify potential Elongin A targets during neuronal differentiation of ES cells, a cDNA microarray analysis comparing embryoid bodies (EBs) derived from Elongin A+/+ ES cells and Elongin A-/- ES cells was performed. Gene expression in EBs derived from Elongin A+/+ and Elongin A-/- ES cells was measured at day 4 after retinoic acid treatment (2 ?M).
2011-07-25 | E-GEOD-30911 | biostudies-arrayexpress