Succinate semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder effecting approximately 350 people around the world. Patients suffering from SSADH deficiency experience language acquisition failure, memory deficiencies, autism, increased aggressive behaviors, and seizures. There is a chemical buildup of both gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) in the neurological system of these patients. The Aldh5a1-/- knock out mouse model of SSADH deficiency shows the same chemical imbalances as the human disease, with additional fatal tonic-clonic seizures at three weeks of age. The elucidation of seizure causing pathways will facilitate treatment of seizure phenotypes in diseases with related epilepsy.
Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency.
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View SamplesThyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown.
Gene signature of the post-Chernobyl papillary thyroid cancer.
No sample metadata fields
View SamplesLoss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors.
Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers.
Disease
View SamplesSkeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues.
Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
Sex, Specimen part, Treatment
View SamplesE-cadherin downregulation in cancer cells is associated with epithelial-to-mesenchymal transition (EMT) and metastatic prowess, but the underlying mechanisms are incompletely characterized. In this study, we probed E-cadherin expression at the plasma membrane as a functional assay to identify genes involved in E-cadherin downregulation. The assay was based on the E-cadherin-dependent invasion properties of the intracellular pathogen Listeria monocytogenes. On the basis of a functional readout, automated microscopy and computer-assisted image analysis were used to screen siRNAs targeting 7,000 human genes. The validity of the screen was supported by its definion of several known regulators of E-cadherin expression, including ZEB1, HDAC1 and MMP14. We identified three new regulators (FLASH, CASP7 and PCGF1), the silencing of which was sufficient to restore high levels of E-cadherin transcription. Additionally, we identified two new regulators (FBXL5 and CAV2), the silencing of which
Novel strategies to enforce an epithelial phenotype in mesenchymal cells.
Age, Specimen part, Cell line, Treatment
View SamplesThe beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics.
Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs.
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View SamplesEscherichia coli release Extracellular Vesicles (EVs) which carry diverse molecular cargo. Pathogenic E.coli EVs contain virulence factors which assist during infection in the host in different mechanisms.The RNA cargo of E.coli EVs has not been assessed in their effect in the host. We used microarray data to asses and compare the global response of bladder cells to EV-RNA from pathogenic E.coli (Uropathogenic UPEC 536) and non-pathogenic E. coli (probiotic Nissle 1917)
Effect of the Extracellular Vesicle RNA Cargo From Uropathogenic <i>Escherichia coli</i> on Bladder Cells.
Disease
View SamplesAnalysis of the coordinated transcriptional reponse to heat shock and ER stress Overall design: mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing, in triplicate, using Illumina HiSeq. The samples were collected from indicated timepoints after exposed to either heat stress or ER stress.
Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells.
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View SamplesAnalysis of the coordinated transcriptional response to unfolded proteins in cytosol and nucleus utilizing mRNA-seq Overall design: mRNA profiles of NIH3T3 cells which stably expressing DD-sfGFP were generated by deep sequencing using Illumina HiSeq2000. The samples were collected from indicated timepoints after Shield-1 removal.
Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells.
No sample metadata fields
View SamplesAnti-TNF-alpha therapy has made a significant impact on the treatment of psoriasis. Despite being designed to neutralize TNF-alpha activity, the mechanism of action of these agents in the resolution of psoriasis remains unclear. The aim of this study was to better understand the mechanism of action of etanercept by examining very early changes in the lesional skin of psoriasis patients. 20 chronic plaque psoriasis patients were enrolled and received 50mg etanercept twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by microarray.
Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling.
Specimen part, Disease, Subject
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