The microbial population that live within the gut of animals influences their physiology. We used axenic and recolonized flies to identify genes whose expression is modulated by the presence of a bacterial flora in the gut.
Drosophila microbiota modulates host metabolic gene expression via IMD/NF-κB signaling.
Specimen part, Treatment
View SamplesDentatorubral-pallidoluysian Atrophy (DRPLA) is a human polyQ disease caused by the expansion of a CAG strech in the atrophin-1 (at-1) gene. In all vertebrates, a second atrophin gene (at-2) is present and it encodes a related protein void of polyQ tracks. In D.melanogaster there is one conserved Atrophin (Atro) gene, ubiquitously expressed, which contains all functional domains of vertebrate Atrophins, including two polyQ stretches. To understand to what extent transcriptional alterations cause neurodegeneration and are linked to the normal functions of Atrophin, we performed a genome wide transcriptional profiling in our Drosophila models, focusing on primary events that precede neurodegeneration.
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
No sample metadata fields
View SamplesInvasion of lymphatic vessels is a key step in the metastasis of primary tumour cells to draining lymph nodes. Recent evidence indicates that such metastasis can be facilitated by tumour lymphangiogenesis, although it remains unclear whether this is a consequence of increased lymphatic vessel numbers or alteration in the properties of the vessels themselves. Here we have addressed this important question by comparing the RNA profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T-241/VEGF-C metastatic fibrosarcoma. Our findings reveal significant changes in the expression of some 792 genes in tumour lymphatics ( 2 fold up/downregulation, p 0.05), involving particularly transcripts associated with junctional adhesion, immunomodulation, extracellular matrix and vessel growth/patterning, several of which we have confirmed by RT-PCR and/or immunohistochemistry. Interestingly, this altered phenotype could not be attributed solely to VEGF-C induced lymphoproliferation, as no similar change in gene expression was reported when human LEC were cultured with VEGF-C in vitro. Moreover, we show that a key protein upregulated in the mouse model, namely the tight junction protein Endothelial Cell Specific Adhesion Molecule (ESAM), is similarly upregulated in tumour lymphatic vessels from 2/2 patients with head and neck squamous cell carcinoma and 4/4 patients with aggressive bladder carcinoma. These findings demonstrate a previously unrecognized influence of tumour environment on lymphatic gene expression and identify candidate tumour specific vessel markers that may prove valuable for either prognosis or therapy.
A novel gene expression profile in lymphatics associated with tumor growth and nodal metastasis.
No sample metadata fields
View SamplesIdentification of genes and pathways relevant to Cervical cancer pathogenesis. The study also aimed at identifying probable mechanistic differences in the low and high HOTAIR expressing cervical cancers patients .
Bridging Links between Long Noncoding RNA HOTAIR and HPV Oncoprotein E7 in Cervical Cancer Pathogenesis.
Age, Specimen part
View SamplesThe nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist.
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
No sample metadata fields
View SamplesHIV-1 and HIV-2 can both infect humans, but HIV-2 causes a slow progressing disease and is well controlled by the immune system for prolonged period of times.
HIV-1 and HIV-2 differentially mature plasmacytoid dendritic cells into IFN-producing cells or APCs.
Treatment, Subject, Time
View SamplesThe nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Common genomic elements promote transcriptional and DNA replication roadblocks.
Subject
View SamplesHlxb9 is a differentiation factor important for neuronal, and pancreatic beta cell differentiation. It is a transcription factor that represses transcription. It's target genes are unknown. The mouse pancreatic beta cell line MIN6 was used to assess the expression of genes de-repressed upon Hlxb9 knockdown.
The embryonic transcription factor Hlxb9 is a menin interacting partner that controls pancreatic β-cell proliferation and the expression of insulin regulators.
Disease, Cell line
View SamplesTissue Factor Pathway Inhibitor-2 is Induced by Fluid Shear Stress in Vascular Smooth Muscle Cells and Affects Cell Proliferation and Survival
Tissue factor pathway inhibitor-2 is induced by fluid shear stress in vascular smooth muscle cells and affects cell proliferation and survival.
No sample metadata fields
View SamplesColorectal cancer cells with TP53 mutation are highly resistant to chemotherapeutics. In order to identify potential chemo-resistance signatures, here; we explored the global gene expression profiles of drug resistant colorectal cancer cell line SW480 upon Floxuridine (FdUrd) treatment using Illumina Human HT-12 v4.0 Expression Beadchip Array. Further, significantly altered genes were subjected to the pathway analysis in GeneCodis3 and crucial signaling pathways were found to be enriched. Upon further functional validations, these pathways could be targeted to enhance therapy in human cancers harboring mutant p53.
Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53.
Sex, Age, Specimen part, Cell line, Treatment
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