We assessed how lack of ISG15 influences the levels of transcripts after IFNa stimulation.
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation.
Specimen part
View SamplesLand plants can reproduce sexually by developing an embryo from a fertilized egg cell. However, embryos can also be formed from other cell types in many plant species. A key question is thus how embryo identity in plants is controlled, and how this process is modified during non-zygotic embryogenesis. The Arabidopsis zygote divides to produce an embryonic lineage and an extra-embryonic suspensor. Yet, normally quiescent suspensor cells can develop a second embryo when the initial embryo is damaged, or when response to the signaling molecule auxin is locally blocked. Here we have used auxin-dependent suspensor embryogenesis as a model to determine transcriptome changes during embryonic reprogramming. We find that reprogramming is complex and accompanied by large transcriptomic changes prior to anatomic changes. This analysis revealed a strong enrichment for genes encoding components of auxin homeostasis and response among misregulated genes. Strikingly, deregulation among multiple auxin-related gene families converged upon re-establishment of cellular auxin levels or response. This suggests a remarkable degree of feedback regulation to create resilience in auxin response during embryo development. Starting from the transcriptome of auxin-deregulated embryos, we identify an auxin-dependent bHLH transcription factor network that mediates the activity of this hormone in suppressing embryo development from the suspensor.
A Robust Auxin Response Network Controls Embryo and Suspensor Development through a Basic Helix Loop Helix Transcriptional Module.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe compared PBMC genomic response to exercise in both early (EB) and late-pubertal boys (LB)
Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.
No sample metadata fields
View SamplesWe compared PBMC genomic response to exercise in both early (EG) and late-pubertal girls (LG)
A brief bout of exercise alters gene expression and distinct gene pathways in peripheral blood mononuclear cells of early- and late-pubertal females.
No sample metadata fields
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of NK cell function by identifying a discrete set of genes in circulating NK cells that were altered by exercise.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of monocytes function by identifying a discrete set of genes in circulating monocytes that were altered by exercise.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesRelatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs), but whether or not exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30-min of constant, heavy (about 80% peak O2 uptake) cycle-ergometer exercise in 12 healthy men (19-29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. Using FDR<0.05 with 95% confidence a total of 526 genes were differentially expressed between before and after exercise. 316 genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, p<0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL32, TNFSF8 and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression.
Effects of 30 min of aerobic exercise on gene expression in human neutrophils.
No sample metadata fields
View SamplesTargeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists. Overall design: Expression profiling by high throughput sequencing
Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity.
Specimen part, Treatment, Subject
View Samples