Cigarette smoking is associated with reduced risk of developing Parkinsons disease (PD). To identify genes that interact with nicotine/smoking, we performed hypothesis-free genome-wide experiments in a paraquat-induced Drosophila model and in a case-control study of PD. We demonstrated that nicotine extends life-span in paraquat-treated Drosophila (P=4E-30). Brain tissue from flies treated with combinations of paraquat and nicotine revealed elevated expression of CG14691 with paraquat which was restored with nicotine co-treatment (P(interaction)=2E-11, P(FDR-adjusted)=4E-7). Independently, variants in the 5 region of SV2C, a human ortholog of CG14691, gave the strongest signal for interaction with smoking (P(interaction)=9E-8). The effect of smoking on PD risk varied six-fold by SV2C genotype (P(heterogeneity)=4E-10). Moreover, SV2C variants identified here were associated with SVC2 gene-expression in the HapMap data. Present results suggest synaptic vesicle protein SV2C plays a role in PD pathogenesis, and that the SV2C genotype may be useful for clinical trials of nicotine for treating PD.
A genetic basis for the variable effect of smoking/nicotine on Parkinson's disease.
Sex, Specimen part
View SamplesNo description.
No associated publication
Sex, Specimen part
View SamplesTo idendentify some smoking-related genes, the in vitro model for malignant transformation was established by exposing BEAS-2B cells to cigarette smoke continuously for 30 passages (S30).
No associated publication
Sex, Specimen part, Cell line
View SamplesThe activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic pmel and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2stimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response.
Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects.
Specimen part
View SamplesTo examine the effect of wtAPE1 and ubiquitin-APE1 fusion proteins on global gene expression. Total RNA from HEK293 derivatives that express vector alone (ctl), wt-APE1, or ubiquitin-APE1 fusion in the presence of doxycycline were analyzed.
No associated publication
Specimen part, Cell line, Treatment
View SamplesThis study crossed Drosophila melanogaster genotypes from four populations to the reference genome line. RNAseq data was then generated to study natural variation in allele specific expression.
No associated publication
Sex, Specimen part, Cell line
View SamplesT-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) share common morphologic and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations suggesting that they may represent two different biological entities. In order to investigate T-LBL and T-ALL biological characteristics we used transcriptional profiling approache. Genome-wide gene expression profiling, performed on 20 T-LBL and 10 T-ALL diagnostic specimens, showed that the two malignancies shared a large fraction of their transcriptional profile while a subset of genes appeared to be differentially expressed in T-LBL versus T-ALL. This gene signature included genes involved in chemotactic responses and angiogenesis which might play a role in the different tumor cell localization suggesting that T-LBL and T-ALL could be two distinct diseases with unique transcriptional characteristics.
No associated publication
Specimen part, Disease
View SamplesIn order to identify genes dysregulated by the aberrant transcriptional activity of RUNX1-RUNX1T1, we used microarrays to determine the effect of this mutation on gene expression during myeloid and erythroid development of normal human progenitor cells.
Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia.
Specimen part
View SamplesSeven-day-old white-light-grown Arabidopsis seedlings were exposed for 15 minutes to polychromatic radiation with decreasing short-wave cut-off in the UV range, transferred back to the standard growth chamber and samples were taken 1 and 6 hours after the start of irradiation.
Genome-wide analysis of gene expression reveals function of the bZIP transcription factor HY5 in the UV-B response of Arabidopsis.
Age, Time
View SamplesGene expression profile in Calu-3 cells infected with MERS-CoV or SARS-CoV
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