In flies, small silencing RNAs are sorted between Argonaute1 (Ago1), the central protein component of the microRNA (miRNA) pathway, and Argonaute2 (Ago2), which mediates RNA interference. Extensive double-stranded character—as is found in small interfering RNAs (siRNAs)—directs duplexes into Ago2, whereas central mismatches, like those found in miRNA/miRNA* duplexes, direct duplexes into Ago1. Central to this sorting decision is the affinity of the small RNA duplex for the Dcr-2/R2D2 heterodimer, which loads small RNAs into Ago2. Here, we show that while most Drosophila miRNAs are bound to Ago1, miRNA* strands accumulate bound to Ago2. Like siRNA loading, efficient loading of miRNA* strands in Ago2 favors duplexes with a paired central region and requires both Dcr-2 and R2D2. Those miRNA and miRNA* sequences bound to Ago2, like siRNAs diced in vivo from long double-stranded RNA, typically begin with cytidine, whereas Ago1-bound miRNA and miRNA* disproportionately begin with uridine. Consequently, some pre-miRNA generate two or more isoforms from the same side of the stem that differentially partition between Ago1 and Ago2. Our findings provide the first genome-wide test for the idea that Drosophila small RNAs are sorted between Ago1 and Ago2 according to their duplex structure and the identity of their first nucleotide. Overall design: Sequencing of small RNAs (either total small RNAs or Ago1-associated small RNAs) in wild-type, dcr-2 and r2d2 mutant flies. Small RNA sequencing, Small RNAs (18-29 nt long), Size selection (18 to 30 nt).
Target RNA-directed trimming and tailing of small silencing RNAs.
Specimen part, Subject
View SamplesHere we report a transcriptomic analysis of fate-restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate-restricted retinal progenitor cells Overall design: Comparison of two FACS-sorted chick retinal progenitor cell populations after electroporation of reporter plasmids and 20hr culture.
Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells.
Specimen part, Subject
View SamplesTargets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Treatment
View SamplesSynthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade
Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens.
Time
View SamplesKarrikins promote seed germination in Arabidopsis thaliana. Completion of germination (protrusion of the radicle) is not observed until ~72 h in dormant wildtype seed under these conditions. We used microarrays to examine karrikin-induced transcriptional changes after 24 h of imbibition. Transcriptional changes may indicate events leading to karrikin-induced germination or karrikin-specific markers.
Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana.
Specimen part, Treatment
View SamplesExposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sex, Age, Specimen part, Treatment
View SamplesExposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases and disorders are not fully understood. The knowledge of global gene expression will help us to devlop early disease or disorder biomarkers for PCB induced health effects.
Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.
Sex, Age, Specimen part, Treatment
View SamplesCurcumin is a potent anti-inflammatory compound capable of preventing chemically induced colitis in mice.
Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent.
Treatment
View SamplesIn intact animals, time of drug administration may be an important factor influencing drug response. Our general goal seeks to incorporate circadian time into the study of corticosteroid regulated gene expression. This study is designed to examine fluctuations in gene expression in skeletal muscle within the 24 hour circadian cycle in normal animals. Circadian time is relevant to designing optimal corticosteroid dosing regimens. Since levels of endogenous steroid exhibit circadian fluctuations, it is our hypothesis that the expression of genes controlled by corticosteroids either directly or indirectly will also exhibit a circadian pattern in normal animals.
Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle.
No sample metadata fields
View SamplesEsophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is generally unresponsive to therapy. African Americans have an increased risk for esophageal squamous cell cancer (ESCC), the subtype that shows marked variation in geographic frequency. To identify key genes involved in ESC carcinogenesis in African Americans we conducted microarray expression profiling and found a significant dysregulation of genes encoding stress response and drug-metabolizing enzymes, mainly in NRF2 pathway. The involvement of NRF2 mediated oxidative damage represent a key step in the evolution of African American ESCC. Loss of activity of these enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence of ESCC in this ethnic group. The differential expression profile also indicates an inflammatory component and tissue regeneration in ESCC tumorigenesis. Together, these findings suggest a remarkable interplay of genetic and environmental factors in the pathogenesis of African American ESCC.
African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.
Race
View Samples