Lyme disease is challenging to diagnose, as clinical manifestations are variable and current tools to detect nucleic acid or antibody responses from Borrelia burgdorferi infection have low sensitivity. Here we conducted the first study of the global transcriptome of patients with Lyme disease to identify potential diagnostic biomarkers. Twenty-nine patients were enrolled and compared to 13 healthy controls at three time points after infection. Fifteen publicly available transcriptome datasets from patients in vivo or infection models in vitro were used to assess specificity of differentially expressed genes (DEGs). We found that Lyme disease results in profound and sustained changes in the patient transcriptomes, with a specific signature that shares =44% DEGs with other infections. Overall design: Gene expression profile from peripheral mononuclear blood cells (PBMC) of Lyme disease patients against healthy controls was undertaken. A total of 29 Lyme disease patients were sampled at 3 time points: acute Lyme pre-treatment (V1), 3 weeks later, immediately following completion of a standard course of antibiotics (V2), and 6 months following treatment completion (V5). 13 healthy controls were also sampled at one time point. Total RNA was extracted from 10e7 PBMC, followed by mRNA purification, paired-end barcode library preparation and sequencing on an Illumina Hiseq 2000.
Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.
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View SamplesFOXO1 acts as a tumor suppressor in solid tumors. The oncogenic PI3K pathway suppresses FOXO1 transcriptional activity by enforcing its nuclear exclusion upon AKT-mediated phosphorylation. We show here abundant nuclear expression of FOXO1 in Burkitt lymphoma (BL), a germinal center (GC) B cell derived lymphoma whose pathogenesis is linked to PI3K activation. Recurrent FOXO1 mutations which prevent AKT targeting and lock the transcription factor in the nucleus are used by BL to circumvent mutual exclusivity between PI3K and FOXO1 activation. Using genome editing in human and mouse lymphomas in which MYC and PI3K cooperate synergistically in tumor development we demonstrate pro-proliferative and anti-apoptotic activity of FOXO1 in BL and identify its nuclear localization as an oncogenic event in GC B cell derived lymphomagenesis.
Nuclear FOXO1 promotes lymphomagenesis in germinal center B cells.
Specimen part, Cell line
View SamplesCD8 T cells play roles in eliminating virus infected targets through cytotoxic effector function and are of great interest from vaccination prespective. Previous studies suggest that the cytokines produced by the CD8 T cells may contribute to the pathological consequences. Because the dengue specific memory T cells strongly secrete cytokines upon in vitro stimulation with heterologous viral antigen, the cytokine storm induced by activated T cells may contribute to the immunopathology of dengue infection. Moreover, the CD8 T cell expansion peaks before or around the time of the peak of clinical symptoms, and the frequency of activated CD8 T cells and cytokine producing cells was somewhat higher in patients with severe forms of dengue disease.
Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India.
Age, Specimen part, Disease, Disease stage
View SamplesGlobal deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle but not adipose tissue or liver led to protection from high-fat diet induced obesity and comorbid sequel.
Calcineurin Links Mitochondrial Elongation with Energy Metabolism.
Sex, Specimen part
View SamplesGenome-wide association studies (GWAS) have been pivotal to increasing our understanding of intestinal disease. However, the mode by which genetic variation results in phenotypic change remains largely unknown, with many associated polymorphisms likely to modulate gene expression. Analyses of expression quantitative trait loci (eQTL) to date indicate that as many as 50% of these are tissue specific. Here we report a comprehensive eQTL scan of intestinal tissue.
Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine.
Sex, Disease
View SamplesThe involvement of skeletal muscle in the process of palatal development in mammals is an example of Waddingtonian epigenetics. Our earlier study showed that the cleft palate develops in the complete absence of skeletal musculature during embryonic development in mice. This contrasts with previous beliefs that tongue obstruction prevents the elevation and fusion of the palatal shelves. We argue that the complete absence of mechanical stimuli from the adjacent muscle, i.e., the lack of both static and dynamic loading, results in disordered palatogenesis. We further suggest that proper fusion of the palatal shelves depends not only on mechanical but also on paracrine contributions from the muscle. The muscle's paracrine role in the process of palatal fusion is achieved through its being a source of certain secreted and/or circulatory proteins.
Role of skeletal muscle in palate development.
Specimen part
View SamplesThe experiment aims to identify mRNAs illustrating the unique nature of the gd T-cell subtype
Human Vδ2 T cells are a major source of interleukin-9.
Specimen part
View SamplesSkeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia.
Role of skeletal muscle in lung development.
Specimen part
View SamplesThis study describes a cDNA microarray analysis that compared developing mouse MyoD-/- limb musculature (MyoD-dependent, innervated by Lateral Motor Column motor neurons) and Myf5-/- back (epaxial) musculature (Myf5-dependent, innervated by Medial Motor Column motor neurons) to the control and to each other, at embryonic day 13.5 which coincides with the robust programmed cell death of motor neurons and the inability of myogenesis to undergo its normal progression in the absence of Myf5 and MyoD that at this embryonic day cannot substitute for each other.
Role of skeletal muscle in motor neuron development.
Specimen part
View SamplesMicroarray whole-transcriptome profiling in HCT116 and HepG2 cells treated with Melicope ptelefolia leaf extract reveals transcriptome profles exhibiting anticancer activity
Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated with <i>Melicope ptelefolia</i> leaf extract reveals transcriptome profiles exhibiting anticancer activity.
Specimen part, Cell line, Treatment
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