using peripheral blood monocytes to identify marker genes for an extensively grown coronary collateral circulation.
Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease.
Sex, Age
View SamplesThe diagnosis of Kawasaki disease (KD) is often difficult to distinguish from adenovirus (HAdV) and Group A streptococcal disease (GAS). We sought to: 1) to define the KD transcriptional signature that can aid in the diagnosis of complete and incomplete KD in children; 2) to identify specific biomarkers that objectively discriminate between KD and other mimicking conditions, including HAdV and 3) to test the prognostic utility of GEP to determine response to IVIG therapy and development of coronary artery lesions (CAL). Methods: Blood RNA samples were analyzed from 76 pediatric patients with complete KD, 13 with incomplete KD, 19 patients with HAdV, 17 patients with GAS disease, and age- and sex-matched healthy controls (HC). We used class comparisons (MW p< 0.01, Benjamini-Hochberg, and 1.25 fold change filter), class prediction, modular analysis and MDTH analyses to define the specificity of the KD profiles and identify markers of severity. Results: Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The KNN class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 96% (95% CI [80%-99%]) sensitivity and 95% [74%-99%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p<0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5,572 respectively; p=0.009]. Conclusion: Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information.
Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.
Sex, Specimen part, Race
View SamplesHigh-throughput sequencing of mRNA from mouse lung infected with 1918 pandemic influenza virus revealed that reactive oxygen species scavenger EUK-207 treatment resulted in decreased expression of inflammatory response genes and increased lung metabolic and repair responses.
Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.
No sample metadata fields
View SamplesCortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons. Overall design: RNA-seq of FACS sorted PV+ and SST+ cortical interneuronals at P8 of wt and conditional Rbfox1 Kos
Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons.
Specimen part, Subject
View SamplesWe investigated the nutritional effects on gene expression in sperm cells of F0 boars from a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs which were investigated in a previous study. The aim of this study was to investigate if the nutrition affects gene expression in sperm cells of differentially fed boars and thus carry information in the form of RNA molecules to the next generation. Four RNA samples from sperm cells of these differentially fed boars were analyzed by RNA-Seq methodology. We found no differential RNA expression in sperm cells of the two groups based on the adjusted P-value > 0.05. Nevertheless, we performed a pathway analysis with 105 genes that differed in gene expression on the level of nominal P-value < 0.05 between the two diet groups. We found a significant number of these differentially expressed genes were enriched for the pathway maps of bacterial infections in cystic fibrosis (CF) airways, glycolysis and gluconeogenesis p.3 and cell cycle_Initiation of mitosis. The GO processes including a significant portion of differentially expressed genes were viral transcription and viral genome expression, viral infectious cycle, cellular protein localization, cellular macromolecule localization, nuclear-transcribed mRNA catabolic process and nonsense-mediated decay. In summary, the results of the pathway analysis are also inconclusive and it is concluded that RNA expression in sperm cells is not significantly affected by extensive supplementation of methylating micronutrients. Consequently, RNA molecules could not be established as epigenetic marks in this feeding experiment. Overall design: Gene expression in sperm cells from differentially fed F0 boars was measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars were used to study transgenerational epigenetic inheritance in a three generation pig pedigree. Therefore it was of interest if the diet affects gene expression in sperm cells which could then be transmitted to next generations.
In search of epigenetic marks in testes and sperm cells of differentially fed boars.
Sex, Specimen part, Subject
View SamplesHuman myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA. Overall design: Human myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA.
The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity.
Specimen part, Cell line, Treatment, Subject, Time
View SamplesIn Pseudomonas aeruginosa, partitioning protein ParB facilitates segregation of newly replicated chromosomes but is not essential for cell survival. Unlike in other bacteria, inactivation of parB leads to major changes of the transcriptome, suggesting that, directly or indirectly, ParB plays a role in regulation of gene expression in this organism.
Increased ParB level affects expression of stress response, adaptation and virulence operons and potentiates repression of promoters adjacent to the high affinity binding sites parS3 and parS4 in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesFacioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-homeodomain transcription factor DUX4 in skeletal muscle cells. Many different cell culture models have been developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human muscle cells. Although results generated using each model are generally consistent, differences have also been reported, making it unclear which model(s) faithfully recapitulate DUX4 and FSHD biology. In this study, we systematically compared RNA-seq data generated from three different models of FSHD—lentiviral-based DUX4 expression in myoblasts, doxycycline-inducible DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4—and show that the DUX4-associated gene expression signatures of each dataset are highly correlated (Pearson's correlation coefficient, r ~ 0.75-0.85). The few robust differences were attributable to different states of cell differentiation and other differences in experimental design. Our study describes a model system for inducible DUX4 expression that enables reproducible and synchronized experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expression. Overall design: We performed a systematic comparison of DUX4-regulated changes in the transcriptome in our inducible codon-altered DUX4 expression system (iDUX4), the endogenous DUX4 expression system (enDUX4), and cells transduced with lentivirus constitutively expressing DUX4 (vDUX4). The specific datasets used in this comparison are as follows: iDUX4 represents a new dataset generated from the MB135 immortalized human myoblasts with the doxycycline inducible codon-altered DUX4 (iDUX4), performed in biological triplicate fourteen hours after DUX4 induction in growth media, with uninduced cells as a control; enDUX4 represents the published dataset of differentiated FSHD myocytes that do or do not express endogenous DUX4, as determined using a DUX4-responsive fluorescent reporter and flow sorting (9); vDUX4 represents a published dataset wherein two different myoblast cell lines (MB135 and 54-1) were transduced with a lentiviral construct that drives constitutive DUX4 expression via the PGK promoter and maintained in growth media for 24 hours (MB135) or 36 hours (54-1) prior to harvesting RNA.
Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy.
Specimen part, Treatment, Subject
View SamplesIn order to understand the complexity of gene regulation downstream of IIS, we did RNA-seq in mixed culture in wild-type, daf-2(e1370), daf-16(mgDf50);daf-2(e1370) and daf-2(e1370);daf-12(m20 and correlated it with ChIP-seq data Overall design: RNA-seq profile of different mutants in mix stage
Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans.
Subject
View SamplesPurpose: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.
Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis.
Specimen part, Cell line
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