In a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on abdominal subcutaneous adipose tisse gene expression. We studied obese adults with features of the metabolic syndrom, n=56. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks.
Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.
Age, Specimen part
View SamplesGene expression changes in response to aging, hyperoxia, hydrogen peroxide, ionizing radiation, and heat stress were compared using microarrays. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hydrogen peroxide, hyperoxia, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.
Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.
Sex, Age
View SamplesIllumina sequencing was used to assay the effect of mifepristone treatment on gene expression in adult Drosophila, including males, virgin females and mated females. Overall design: Males of strain w[1118]; p53B[6] were crossed to virgins of w[1118]; rtTA(3)E2 and progeny males and virgins were collected over 48 hours. One half of the virgins were mated to w[1118] males at ratio of 1:1 virgins to males for 4 days. Mated females were then separated from the w[1118] males. The mated females, males and virgins females were then maintained at approximately 20 flies per vial, on food with and without supplementation with 160ug/ml mifepristone for 12 days. Total fly RNA was isolated from 20 animals per sample. Three replicate samples were generated for each type of flies: males, mated females and virgin females.
The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila.
Specimen part, Subject
View SamplesPromoter recognition by bacterial RNA polymerase is mediated by subunits, which assemble transiently to RNA polymerase core enzyme (E) during transcription initiation. subunits drive transcription of specific sets of genes by allowing RNA polymerase to interact with different promoter sequences. However, 70, the housekeeping subunit, and S, an alternative subunit mainly active during slow growth and in response to cellular stresses, appear to recognize almost identical promoter sequences, raising the question of how promoter selectivity is achieved in the bacterial cell. To identify sequence determinants for selective promoter recognition, we performed a run-off/microarray experiment (ROMA): in vitro transcription experiments were carried out with RNA polymerase saturated either with 70 (E70) or with S (ES) using the whole Escherichia coli genome as DNA template, and transcript levels were determined by microarray analysis. We found that several genes associated with bacterial growth (e.g., ribosomal operons) were transcribed more efficiently by E70. In contrast, ES transcribed preferentially genes involved in stress responses, secondary metabolism, as well as regulatory RNAs and intergenic regions with yet unknown function. Genes preferentially recognized in vitro by ES showed reduced expression in ES -deficient mutant strain of E. coli. Sequence comparison of E70- versus ES dependent promoters confirms that the presence of a -35 sequence and the relative location of UP elements affect promoter interaction with either form of RNA polymerase, and suggests that a G/C bias in the -2/+1 nucleotides would favour efficient promoter recognition by E70.
In vitro transcription profiling of the σS subunit of bacterial RNA polymerase: re-definition of the σS regulon and identification of σS-specific promoter sequence elements.
Disease
View SamplesObesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of tumors for which the patients body mass index (BMI) was ascertained. Sample profiles were stratified according to patients obesity phenotype defined as normal (BMI <25), overweight (BMI 25-29.9), or obese (BMI>30). Widespread alterations in gene expression were evident in breast tumors from obese patients as compared to tumors from other patients, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes.
A gene transcription signature of obesity in breast cancer.
Age, Disease, Disease stage, Race
View SamplesWe used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity.
Gene expression-based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development.
Sex, Specimen part, Treatment
View SamplesAcute lung rejection is a risk factor for chronic rejection, jeopardizing the long-term survival of lung transplant recipients. At present, acute rejection is diagnosed by transbronchial lung biopsies, which are invasive, expensive, and subject to significant sampling error. In this study, we sought to identify groups of genes whose collective expression in BAL cells best classifies acute rejection versus no-rejection. BAL samples were analyzed from 32 unique subjects whose concurrent histology showed acute rejection (n=14) or no rejection (n=18). Global BAL cell gene expression was measured using Affymetrix U133A microarrays. The nearest shrunken centroid method with 10-fold cross validation was used to define the classification model. 250 runs of the algorithm were performed to determine the range of misclassification error and the most influential genes in determining classifiers. The estimated overall misclassification rate was below 20%. Seven transcripts were present in every classifier and 52 transcripts were present in at least 70% of classifiers; these transcripts were notable for involvement with T-cell function, cytotoxic CD8 activity, and granulocyte degranulation. The proportions of both lymphocytes and neutrophils in BAL samples increased with increasing probability of acute rejection; this trend was more pronounced with neutrophils. We conclude that there is a prominent acute rejection-associated signature in BAL cells characterized by increased T-cell, CD8+ cytotoxic cell, and neutrophil gene expression; this is consistent with established mechanistic concepts of the acute rejection response.
Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier.
No sample metadata fields
View SamplesThe ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep-sequencing of ribosome-protected mRNA fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and novel translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation. We also define a new class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes. Overall design: Examination of translation in mouse embryonic stem cells and during differentiation into embryoid bodies
Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins.
Cell line, Treatment, Subject
View SamplesBronchoalveolar lavage samples collected from lung transplant recipients. Numeric portion of sample name is an arbitrary patient ID and AxBx number indicates the perivascular (A) and bronchiolar (B) scores from biopsies collected on the same day as the BAL fluid was collected. Several patients have more than one sample in this series and can be determined by patient number followed by a lower case letter. Acute rejection state is determined by the combined A and B score - specifically, a combined AB score of 2 or greater is considered an acute rejection.
Gene expression profiling of bronchoalveolar lavage cells in acute lung rejection.
No sample metadata fields
View SamplesInfluenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and economy. Therefore, a large effort has been devoted to the development of new anti-influenza drugs directed to viral targets, as well as to the identification of cellular targets amenable for anti-influenza therapy. Here we describe a new approach to identify such potential cellular targets by screening collections of drugs approved for human use. We reasoned that this would most probably ensure addressing a cellular target and, if successful, the compound would have a well known pharmacological profile. In addition, we reasoned that a screening using a GFP-based recombinant replicon system would address virus trancription/replication and/or gene expression, and hence address a stage in virus infection more useful for inhibition. By using such strategy we identified Montelukast as an inhibitor of virus gene expression, which reduced virus multiplication in virus-infected cells but did not alter virus RNA synthesis in vitro or viral RNA accumulation in vivo. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated or not with Montelukast, we identified the PERK-mediated unfolded protein response as the pathway responsible for Montelukast action. Accordingly, PERK phosphorylation was inhibited in infected cells but stimulated in Montelukast-treated cells. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection. Overall design: Comparison of gene expression measured by deep sequencing (single-ends, 50nt, RNA-seq) of "Infected", "Not infected", "Infected+Montelukast" and "Not infect+Montelukast" in human A549 cells. Infected means "Infected with influenza virus".
Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition.
No sample metadata fields
View Samples