To examine the role of SPS1 in mammals, we generated a Sps1 knockout mouse and found that systemic SPS1 deficiency was embryonic lethal. Embryos were clearly underdeveloped by E8.5 and virtually reabsorbed by E14.5. Removal of Sps1 specifically in hepatocytes using Albumin-cre preserved viability, but significantly affected expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione-S-transferase omega 1. To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma cell line, which recapitulated changes in the glutathione system proteins. We further found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 has a role in supporting and/or sustaining cancer. In addition, the increased ROS levels observed in F9 SPS1/GLRX1 deficient cells were reversed and became more like those in F9 SPS1 sufficient cells by overexpressing mouse or human GLRX1. The results suggest that SPS1 is an essential mammalian enzyme with roles in regulating redox homeostasis and controlling cell growth.
Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals.
Sex, Specimen part
View SamplesThis study focused on transcription in the medial PFC (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized on tasks, attentional set shift and spatial memory, which depend on the mPFC and hippocampus, respectively. Differences in transcription associated with age and cognitive function were examined using RNA sequencing to construct transcriptomic profiles for the mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging associated with increased expression of immune and defense response genes and a decline in synaptic and neural activity genes. Importantly, we provide evidence for region specific transcription related to behavior. In particular, expression of transcriptional regulators and neural activity-related immediate-early genes (IEGs) are increased in the mPFC of aged animals that exhibit delayed set shift behavior; relative to age-matched animals that exhibit set shift behavior similar to younger animals. Overall design: The study contains 11 young and 20 aged rats for the mPFC and CA1 samples, which were used to investigate expression patterns associated with aging and behavior. White matter samples were used to investigate an age-related effect with 8 young and 9 aged rats.
Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex.
No sample metadata fields
View SamplesStaphylococcus aureus is a major human pathogen and resistant to numerous clinically used antibiotics. The first antibiotic developed for S. aureus infections was the nonribosomal petide secondary metabolite penicillin. We discovered cryptic nonribosomal peptide secondary metabolites, the aureusimines, made by S. aureus itself that are not antibiotics, but function as small molecule regulators of virulence factor expression. Using established rules and codes for nonribosomal peptide assembly we predicted these nonribosomal peptides, and used these predictions to identify them from S. aureus culture broths. Functional studies using global microarray and mouse bacteremia models established that the aureusimines control virulence factor expression and are necessary for productive infections. This is the first report of the aureusimines and has important implications for the treatment of drug resistant S. aureus. Targeting aureusimine synthesis may provide novel anti-infectives.
Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence.
No sample metadata fields
View SamplesAn evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with ADH-1 followed by melphalan in the setting of isolated limb infusion
Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma.
Disease, Disease stage, Treatment
View SamplesRNA was obtained from histologically normal bronchial epithelium of smokers during time of clinical bronchoscopy from relatively accessible airway tissue. Gene expression data from smokers with lung cancer was compared with samples from smokers without lung cancer. This allowed us to generate a diagnostic gene expression profile that could distinguish the two classes. This profile could provide additional clinical benefit in diagnosing cancer amongst smokers with suspect lung cancer.
Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
Sex, Age, Race
View SamplesTranscriptional profiling after inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells
Transcriptional profiling in response to inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells.
Specimen part
View SamplesAt least six histone H1 variants exist in mammalian somatic cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be involved in the active regulation of gene expression. It is not well known whether the different variants have specific roles or regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. A different subset of genes is altered in each H1 knock-down.
Depletion of human histone H1 variants uncovers specific roles in gene expression and cell growth.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
Specimen part, Subject
View SamplesTranscriptional profiling of IAS subjects
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
Specimen part, Subject
View SamplesAbstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis.
Platelets and platelet-like particles mediate intercellular RNA transfer.
Specimen part, Cell line
View Samples