Ob/ob mice were given 0, 12.5 or 25 ng/hr leptin through an osmotic pump. After 12 days, livers RNA was prepared and illumina microarrays were done. We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma [glucose] and [insulin]. We found that a leptin dose of 12.5 ng/hour significantly lowers blood glucose and that 25 ng/hour of leptin normalizes plasma glucose and insulin without significantly reducing body weight, thus establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 as being regulated by leptin with a similarly high potency. Over-expression of IGFBP2 by an adenovirus reversed diabetes in insulin resistant ob/ob, Ay/a and diet-induced obese mice (DIO), as well as insulin deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a three-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment in ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
Antidiabetic effects of IGFBP2, a leptin-regulated gene.
Specimen part, Time
View SamplesSudden death syndrome (SDS) caused by the fungal pathogen, Fusarium virguliforme, is a major threat to soybean production in North America. There are two major components of this disease: (i) root necrosis and (ii) foliar SDS. Root symptoms consist of root necrosis with vascular discoloration that extends upto several nodes and internodes into the stem. Foliar SDS symptom is characterized by interveinal chlorosis and necrosis in leaves which finally curl and fall off, and in severe cases by flower, pod abscission and immature seed formation. A major toxin involved in initiating foliar SDS has been identified. Nothing is known about how root necrosis develops. In order to unravel the mechanisms used by the pathogen to cause root necrosis, the transcriptome of the pathogen in infected soybean root tissues of a susceptible cultivar (Williams 82) was investigated. The transcriptomes of the germinating conidia and mycelia were also examined. Of the 14,845 predicted F. virguliforme genes, we observed that 12,017 (81%) were expressed in germinating conidial spores and 12,208 (82%) in mycelia and 10,626 (72%) in infected soybean roots. Of the 10,626 genes induced in infected roots, 224 were transcribed only following infection. Expression of several infection-induced genes encoding enzymes with oxidation-reduction properties suggests that degradation of antimicrobial compounds such as the phytoalexin, glyceollin could be important in establishing the biotrophic phase. Enzymes with hydrolytic and catalytic activities could play an important role in the transitioning of the pathogen from biotrophic to necrotrophic phase. Expression of a large number of genes encoding enzymes with catalytic and hydrolytic activities during late infection stage suggests cell wall degradation by some of these enzymes could be involved in root necrosis and establishing the necrotrophic phase in this pathogen. Overall design: RNA-seq data for Fusarium virguliforme Mont-1 germinating conidial spores, mycelia and soybean root tissue 3 and 5 days or 10 and 24 days post water incubation or infection with Fusarium virguliforme Mont-1 conidial spores. Raw data for Fusarium virguliforme Mont-1 germinating conidial spores and mycelia are not available due to server failure.
Tanscriptomic Study of the Soybean-Fusarium virguliforme Interaction Revealed a Novel Ankyrin-Repeat Containing Defense Gene, Expression of Whose during Infection Led to Enhanced Resistance to the Fungal Pathogen in Transgenic Soybean Plants.
Specimen part, Subject
View SamplesBackground: Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear.
Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic landscape of meningiomas.
Sex, Age, Specimen part, Disease stage
View SamplesMeningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed global genetic and genomic analysis of 85 meningioma samples of various grades.
Genomic landscape of meningiomas.
Sex, Age, Specimen part, Disease stage
View SamplesFerrets were experimentaly infected with influenza A/California/07/2009. RNA samples from lungs and lymph nodes were analyzed by Illumina sequencing.
Sequencing, annotation, and characterization of the influenza ferret infectome.
No sample metadata fields
View SamplesPandemic H1N1 influenza A Human infection leads to symptoms ranging from mild to severe with lower respiratory complications observed in a small but significant number of infected individuals. Microarray analysis of the lymph nodes from ferrets infected with A/California/07/2009 shows intense gene upregulation during days 3 and 5 post-infection, and followed by marked downregulation during days 7 and 14 post infection. Gene expression profiles during the upregulation phase show intense chemokine activity, cell replication and activation of the lymphocyte-related signaling pathways.
Sequencing, annotation, and characterization of the influenza ferret infectome.
Specimen part, Time
View SamplesMuscle denervation due to injury, disease or aging results in impaired motor function. Restoring neuromuscular communication requires axonal regrowth and regeneration of neuromuscular synapses. Muscle activity inhibits neuromuscular synapse regeneration. The mechanism by which muscle activity regulates regeneration of synapses is poorly understood. Dach2 and Hdac9 are activity-regulated transcriptional co-repressors that are highly expressed in innervated muscle and suppressed following muscle denervation. Here, we report that Dach2 and Hdac9 inhibit regeneration of neuromuscular synapses. Importantly, we identified Myog and Gdf5 as muscle-specific Dach2/Hdac9-regulated genes that stimulate neuromuscular regeneration in denervated muscle. Interestingly, Gdf5 also stimulates presynaptic differentiation and inhibits branching of regenerating neurons. Finally, we found that Dach2 and Hdac9 suppress miR206 expression, a microRNA involved in enhancing neuromuscular regeneration. Overall design: RNAseq on innervated and 3 day denervated adult soleus muscle from wildtype mice is compared with that from 3 day denervated soleus muscle from Dach2/Hdac9 deleted mice to identify Dach2/Hdac9-regulated genes.
Dach2-Hdac9 signaling regulates reinnervation of muscle endplates.
No sample metadata fields
View SamplesAnalysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA.
Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dual Regulatory Functions of SUFU and Targetome of GLI2 in SHH Subgroup Medulloblastoma.
Specimen part
View Samples