Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Age, Specimen part, Treatment
View SamplesHepatitis C Virus (HCV) has a extremely narrow host cell tropism and robustly infects only very few cell lines, most importantly the human hepatoma cell line Huh7. This cell line was isolated from a 57-year old Japanese male with fulminant hepatitis. Different subclones and passages of the Huh7 cell line show up to 1000-fold differences in HCV replication efficiency (permissiveness). In this experiment, we sought to identify factors responsible for these differences by correlating gene expression from eight different uninfected Huh7 variants with their respective HCV permissiveness. HCV replication efficiency was determined using electroporation of a subgenomic luciferase reporter replicon (genotype 1b, "con1/ET") and measuring luciferase activity at 48h post transfection normalized to the input value at 4h p.t.. "Relative permissiveness" of cell lines corresponds to their replication efficiency, normalized to the efficiency in the lowest permissive cells (Huh7 p13 and p28).
Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle.
Specimen part
View SamplesRNA was isolated from FFPE samples of IDH1 mutant, WT tumors and normal brains Overall design: Determination of the glioma subtype in IDH1 mutant and WT tumors
Mutant IDH1 Promotes Glioma Formation In Vivo.
Specimen part, Subject
View SamplesAll major types of interferon (IFN) efficiently inhibit hepatitis C virus (HCV) replication in vitro and in vivo. Remarkably, HCV replication is not sensitive to IFN in the hepatoma cell line Huh6, despite an intact signaling pathway. We performed transcriptome analyses between Huh6 and Huh-7 to identify effector genes of the IFN response and thereby identified the DExD/H box helicase DDX60L as a restriction factor of HCV replication. DDX60L and its homolog DDX60 were both induced upon viral infection and IFN treatment in primary human hepatocytes. However, exclusively DDX60L knockdown increased HCV replication in Huh-7 cells, and rescued HCV replication from type II IFN as well as type I and III IFN treatment, suggesting that DDX60L is an important effector protein of the innate immune response against HCV. DDX60L had no impact on replication of hepatitis A virus (HAV), but severely impaired production of lentiviral vectors, arguing for a potential antiretroviral activity. Detection of endogenous DDX60L protein turned out to be difficult due to instability. DDX60L knockdown did not alter interferon stimulated gene (ISG) induction after IFN treatment, suggesting that it is a direct effector of the innate immune response. It most likely inhibits viral RNA replication, since we found no impact of DDX60L on translation or stability of HCV subgenomic replicons, nor additional impact on entry and assembly of infectious virus. Similar to its homolog DDX60, DDX60L had a moderate impact on retinoic acid-inducible gene I (RIG-I)-dependent activation of innate immunity arguing for additional functions in the sensing of viral RNA.
DDX60L Is an Interferon-Stimulated Gene Product Restricting Hepatitis C Virus Replication in Cell Culture.
Cell line, Treatment
View SamplesBackground: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers.
Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium.
Specimen part, Disease, Disease stage
View SamplesCerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparuminfected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor B (NF-B) activation cascade. The proinflammatory NF-B pathway was central to the regulation of the P falciparummodulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparuminfected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium.
No sample metadata fields
View SamplesP. falciparum NF54 proliferates under micro-aerophilic conditions in an environment of 3% O2, 4% CO2, 93% N2. This strain was gradually adapted to proliferate under standard tissue culture conditions of 5% CO2/95% air (~19% O2) to generate P. falciparum HOX. We compared global gene expression profiles of the two strains to identify differences, if any.
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
No sample metadata fields
View SamplesViruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4, PPAR, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4 reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPAR or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity.
Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection.
Age, Specimen part
View SamplesDAZAP1 was depleted in culterd HEK 293T cells using shRNA and the resulting poly A RNA were isolated c-DNA library constructed and paired end sequenced on illumina Hi-seq 2000 platform the data was compared to a control shRNA depleted cell Overall design: Gene expression and splicing switches upon DAZAP1 knockdown
The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Malat1 is not an essential component of nuclear speckles in mice.
Age, Specimen part
View Samples