Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes.
Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome.
Sex, Age, Specimen part
View SamplesBackground and aim: The Insulin-like growth factor (IGF) axis is increasingly suggested to be involved in fatty liver disease and progression. We identified IGFBP2 as transcriptional regulatory effect network in liver steatosis and conducted a translational approach of its role in liver pathology from mouse to human, and whether it is influenced by conventional clinical intervention that mitigate hepatic steatosis. Methods: Primary hepatocytes from either C57Bl6 controls, alb-SREBP-1c mice with moderate transgene induced hepatic lipid accumulation or aP2-SREBP-1c mice with massive ectopic hepatic lipid accumulation, were analyzed to identify regulatory networks based on differentially regulated hepatic gene expression. In a translational approach, serum of morbidly obese patients with and without diabetes and biopsy-proven NAFLD were used for ELISA-based validation of mouse data. Moreover, sera of patients undergoing intervention were analyzed and correlated to liver fat content. Results: Comparative knowledge-based transcriptome analysis identified IGFBP2 as top score regulatory effect network between moderate and aggravated fatty liver in mouse models. The reduced expression of IGFBP2 in aP2-SREPB-1c progressed fatty liver associated with Igfbp2 promoter hypermethylation. Reduced secretion of IGFBP2 from aP2-SREBP-1c hepatocytes was reflected in the circulation of the animals. In this phenotype, reductions of IGFBP2 were accompanied by reduced fatty acid oxidation and increased methyltransferase and SIRT activity. Physiologically, IGFBP2 has no direct impact on lipid metabolism but might modulate IGF1 action on de novo lipogenesis. In humans, IGFBP2 levels declined from non-obese men to morbidly obese men with NAFLD and NASH. In intervention study reductions in liver fat correlated with restoration of IGFBP2 serum levels to values found in healthy individuals in morbidly obese patients following bariatric surgery. Conclusion: In hepatic metabolism changes of IGFBP2 abundance is connected to lipid metabolism whereas changes in IGFBP2 secretion were directly reflected in the circulation. IGFBP2 serum concentration correlates with the degree of fatty liver, which seems to be related to plasticity of the adipose tissue. These data provide IGFBP2 as a potential non-invasive biomarker for fatty liver disease directly reflecting the degree of impaired liver function with the potential to indicate progressed fatty liver disease.
Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.
Sex, Age
View SamplesParkinsons Disease is a multi-system, disabling progressive neurodegenerative condition. Clinical progression is highly heterogeneous and, thus far, there are not available biomarkers to accurately predict the rate of disease progression. Thus, identifying molecular signatures that allow discriminating between different progression rates might significantly assist the therapeutic strategy, and enable improved outcomes in clinical trials.
Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.
Sex, Specimen part
View SamplesThe expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the Col-0, ARF10 and mARF10 sample groups allow the identification of genes regulated by ARF10.
Repression of AUXIN RESPONSE FACTOR10 by microRNA160 is critical for seed germination and post-germination stages.
No sample metadata fields
View SamplesBackground:
Role of IFN-gamma and IL-6 in a protective immune response to Yersinia enterocolitica in mice.
Sex
View SamplesTo characterize the role of the ERI-6/7 helicase in endogenous small RNA pathways in C. elegans, small RNA populations from null alleles of eri-6 and eri-7, and from mutants of known endogenous RNAi pathway factors, eri-1 and ergo-1, were determined by deep sequencing, and compared to wild type. Overall design: Small RNA analysis in wild type and eri-1, ergo-1, eri-6 and eri-7 mutant C. elegans strains.
The ERI-6/7 helicase acts at the first stage of an siRNA amplification pathway that targets recent gene duplications.
Cell line, Subject
View SamplesArgonaute-associated siRNAs and Piwi-associated piRNAs have overlapping roles in silencing mobile genetic elements in animals. In C. elegans, mutator-class (mut) genes mediate siRNA-guided repression of transposons as well as exogenous RNA-directed gene silencing (RNAi), but their roles in endogenous RNA silencing pathways are not well understood. To characterize the endogenous small RNAs dependent on mutator-class genes, small RNA populations from a null allele of mut-16, as well as a regulatory mut-16(mg461) allele that disables only somatic RNAi, were subjected to deep sequencing. Overall design: Small RNA analysis in wild type and mut-16 mutant C. elegans strains
mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans.
Cell line, Subject
View SamplesCryopreservation consists of preserving living cells or tissues at <-100C and has many applications in, for instance, stem cell and organ banking. Cryoprotectant agents, like ethylene glycol, are required for successful cryopreservation but have toxic side effects due to largely unknown mechanisms. In this work, we studied the toxicity of ethylene glycol in Human Umbilical Vein Endothelial Cells (HUVECs). Exposing cells to 60% ethylene glycol for two hours at 4C resulted in a slight decrease in cell growth, suggesting a modest toxicity of ethylene glycol and that HUVECs do not exhibit particular sensitivity to it. Gene expression analysis with whole genome micro-arrays revealed signatures indicative of a generalized stress response at 24 hours after stress and recovery at 72 hours, involving signaling pathways, glycoproteins, and genes involved in extracellular and transmembrane functions. These results reveal a new paradigm and signatures for future experiments in elucidating the toxicity effects of ethylene glycol in vascular endothelial cells.
Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol.
Specimen part, Treatment
View SamplesTotal RNA samples from three replicate cultures of wild type and mutant yeast strains was isolated and expression profile done using Affymetrix arrays. Comparsion between the samples indicate how mutation in a single amino acid residue in histone H4 (H4R45H) affects gene expression in yeast. Such a mutation in histone H4 is known to generate a specific class of mutants called SWI/SNF independent (SIN) mutants, and the mutants were identified by their ability to carry out transcription in the absence of yeast chromatin remodeling complex SWI/SNF. SIN mutations are known to affect higher order chromatin structure and the comparative expression profile would help identification of genes which get affected by such altered chromatin landscape.
A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast.
No sample metadata fields
View SamplesIn a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the -secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity.
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice.
Sex, Age
View Samples