Ustilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses.
Two linked genes encoding a secreted effector and a membrane protein are essential for Ustilago maydis-induced tumour formation.
Specimen part, Disease, Disease stage
View SamplesExpression data were generated on 136 subjects from the COPDGene study using Affymetrix microarrays. Multiple linear regression with adjustment for covariates (gender, age, body mass index, family history, smoking status, pack years) was used to identify candidate genes and Ingenuity Pathway Analysis was used to identify candidate pathways.
Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease.
Sex, Specimen part
View SamplesThe macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
No sample metadata fields
View SamplesThe macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown.
Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.
No sample metadata fields
View SamplesA375P melanoma cells were treated with 1uM of the MEK inhibitor PD184352 or 0.4uM of the V600EBRAF inhibitor PLX4720 for 2hr, 6hr and 24hrs.
Identification of direct transcriptional targets of (V600E)BRAF/MEK signalling in melanoma.
Cell line, Treatment, Time
View SamplesThe Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma. While the precise mechanisms underlying the ALT pathway are unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3, correlate with ALT status. ATRX and DAXX facilitate deposition of the histone variant H3.3 within heterochromatic regions including the telomere suggesting that loss of ATRX, DAXX, and/or H3.3 lead to defects in heterochromatin maintenance at telomeres, ultimately contributing to ALT activity. Previous studies have detected genetic mutations in ATRX, DAXX, and H3.3 in ALT cell lines and tumor samples. However, a subset of ALT samples show loss of ATRX or DAXX protein expression or localization without evidence of genetic alterations, indicating a role for other defects in ATRX/DAXX/H3.3 function. Here, using Next Generation Sequencing, we identified a novel gene fusion event between DAXX and the kinesin motor protein, KIFC3, which leads to the translation of a chimeric DAXX-KIFC3 fusion protein. Here, we demonstrate that the fusion of KIFC3 to DAXX leads to defects in DAXX function and likely perpetuates ALT activity. These data highlight a previously unrecognized mechanism of DAXX inactivation in ALT positive osteosarcoma and provide rationale for thorough and comprehensive analyses of ATRX/DAXX/H3.3 proteins in ALT positive cancers. Overall design: 13 cell lines sequenced in triplicate, totaling 39 sequencing samples
Identification of a novel gene fusion in ALT positive osteosarcoma.
Cell line, Subject
View SamplesMicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.
Specimen part
View SamplesTo elucidate the mechanism(s) underlying the synergistic interaction between ETV6 and NFKB1, we analyzed the genome-wide transcriptional consequences of single and double knock-downs of the two TFs in U251 cells.
Causal Mechanistic Regulatory Network for Glioblastoma Deciphered Using Systems Genetics Network Analysis.
Cell line
View SamplesThe development of high-throughput genomic technologies has revealed that a large fraction of the genomes of eukaryotes is associated with the expression of noncoding RNAs. One class of noncoding RNA, the cis-natural antisense transcripts (cis-NATs), are particularly interesting as they are at least partially complementary to the protein-coding mRNAs. Although most studies described cis-NATs involved in the regulation of transcription, a few reports have shown recently that cis-NATs can also regulate translation of the cognate sense coding genes in plants and mammals. In order to identify novel examples of translation regulator cis-NATs in Arabidopsis thaliana, we designed a high-throughput experiment based on polysome profiling and RNA-sequencing. Expression of cis-NATs and translation efficiency of the cognate coding mRNAs were measured in roots and shoots in response to various conditions, including phosphate deficiency and treatment with phytohormones. We identified several promising candidates, and validated a few of them experimentally, in Arabidopsis thaliana transgenic lines over-expressing in trans the translation regulator candidate cis-NATs. Overall design: total RNA and polysomal RNA was sequenced from Arabidopsis thaliana whole seedlings grown in high or low pohsphate content, or from roots or shoots from seedlings treated or not with different phytohormones (Ctrl, IAA, ABA,MeJA and ACC). 3 biological replicates were analyzed for each of the 12 experimental conditions.
Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions.
Specimen part, Treatment, Subject
View SamplesThe molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmanns Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness.
An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures.
No sample metadata fields
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