The IFN type I signature is present in over half of primary Sjgrens syndrome (pSS) patients and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered to be the source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of pSS patients.
Contrasting expression pattern of RNA-sensing receptors TLR7, RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary Sjögren's syndrome.
Sex, Specimen part, Disease, Disease stage
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesLymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process.
Prediction of lymph node involvement in breast cancer from primary tumor tissue using gene expression profiling and miRNAs.
Disease, Disease stage
View SamplesSaccharomyces cerevisiae flocculation occurs when fermentable sugars are limiting and is therefore considered as a way to enhance the survival chance of Flo-expressing yeast cells. In this paper, the role of Flo1p in mating was demonstrated by showing that the mating efficiency, which contributes to the increased survival rate as well by generating genetic variability, is increased when cells flocculate. This was revealed by liquid growth experiments in a low shear environment and differential transcriptome analysis of FLO1 expressing cells compared to the non-flocculent wild-type cells. The results show that a floc provides a uniquely organized multicellular ultrastructure that provides a suitable microenvironment to induce and perform cell conjugation.
Molecular mechanism of flocculation self-recognition in yeast and its role in mating and survival.
No sample metadata fields
View SamplesA small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published.
Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target.
Specimen part, Cell line
View SamplesHistological classification of gliomas guides treatment decisions. Because of the high interobserver variability, we aimed to improve classification by performing gene expression profiling on a large cohort of glioma samples of all histological subtypes and grades. The seven identified intrinsic molecular subtypes are different from histological subgroups and correlate better to patient survival. Our data indicate that distinct molecular subgroups clearly benefit from treatment. Specific genetic changes (EGFR amplification, IDH1 mutation, 1p/19q LOH) segregate in -and may drive- the distinct molecular subgroups. Our findings were validated on three large independent sample cohorts (TCGA, REMBRANDT, and GSE12907). We provide compelling evidence that expression profiling is a more accurate and objective method to classify gliomas than histology.
Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology.
Sex, Age, Specimen part
View Samples56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Overall design: Cell lines were profiled in their baseline, unperturbed state.
Modeling precision treatment of breast cancer.
No sample metadata fields
View Samples