The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we apply this approach to inflammatory bowel disease by examining groups of Crohn's disease (CD) and ulcerative colitus (UC) patients. The induced plasma induced signatures are compared to those of Type 1 diabetes patients (RO T1D) as well as unrelated healthy controls (uHC).
Plasma-induced signatures reveal an extracellular milieu possessing an immunoregulatory bias in treatment-naive paediatric inflammatory bowel disease.
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View SamplesBackgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Subject
View SamplesRNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells. Overall design: Splenic follicular IgD low and IgD high , and MZ B cells were sorted by FACS from naïve 8-10 weeks old mice. Total RNA was isolated from the sorted cells using RNAqueous® -4PCR kit and RNA sequencing was performed. Splenocytes from five mice were pooled for each sorting. Three independent sorting was performed for each B cell subset.
Mature IgD<sup>low/-</sup> B cells maintain tolerance by promoting regulatory T cell homeostasis.
Specimen part, Cell line, Subject
View SamplesHepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, -catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Specimen part
View SamplesCellular senescence is a tumor suppressor mechanism, and immortalization facilitates neoplastic transformation. Both mechanisms may be highly relevant to hepatocellular carcinoma (HCC) development and its molecular heterogeneity. Cellular senescence appears to play a major role in liver diseases. Chronic liver diseases are associated with progressive telomere shortening leading senescence that is observed highly in cirrhosis, but also in some HCC. We previously described the generation of immortal and senescence-programmed clones from HCC-derived Huh7 cell line.
Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.
Sex, Specimen part
View SamplesThe goal was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs (FDR = 10%) and 952 trans-eQTLs, we focused our analysis on Pb-sensitive “trans-eQTL hotspots”. Overall design: 158 randomly selected Drosophila Synthetic Population Resource (A2) samples (control 79 samples and Pb-treated) without replicates
Identification of Splicing Quantitative Trait Loci (sQTL) in <i>Drosophila melanogaster</i> with Developmental Lead (Pb<sup>2+</sup>) Exposure.
Cell line, Subject
View SamplesOptic neuritis (ON) is a common manifestation of multiple sclerosis (MS); it appears as the presenting symptom in about 25% of MS patients and occurs in 3070% of patients with MS during the course of their illness
The role of B cells in the early onset of the first demyelinating event of acute optic neuritis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesSpontaneous neural repair from endogenous neural stem cells (NSCs) occurs in response to central nervous system (CNS) injuries or diseases to only a limited extent from endogenous NSCs niches. Uncovering the mechanisms that control neural repair and can be further manipulated to promote towards oligodendrocyte progenitors cells (OPCs) and myelinating oligodendrocytes is a major objective.
Prickle1 as positive regulator of oligodendrocyte differentiation.
Sex, Age, Specimen part, Time
View SamplesWildtype B6, Rag1-/- B6 and Rag1-/- B6 mice harboring the 225.4 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron
IgA response to symbiotic bacteria as a mediator of gut homeostasis.
No sample metadata fields
View SamplesBackground: The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable treating physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods: In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results: We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p< 0.001). If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used, resulting in a prediction with a resolution of 50 days as to the timing of the next relapse. The error rate of this predictor was 2.3 fold lower than the error rate of random predictions (error rate = 0.35, p<0.001). The predictors were further evaluated and found effective not only in untreated patients but were also valid for MS patients which subsequently received immunomodulatory treatments after the initial testing (the error rate of the first level predictor was < 0.18 with p<0.001 for all the patient groups). Conclusions: We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature
Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells.
Sex, Age, Specimen part, Disease, Disease stage
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