Gene expression from WT and NFAT5 KO primary macrophage cultures.
Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sex, Specimen part
View SamplesDelineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., PTSD-like) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (421%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sex, Specimen part
View SamplesDelineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., PTSD-like) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (421%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sex, Specimen part
View SamplesEarly diagnosis of transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease modifying therapies. Early diagnosis is often difficult because the patient exhibits apparent symptoms of polyneuropathy or cardiomyopathy, but has a negative amyloid biopsy. Thus, there is a pressing need for more objective, quantitative diagnostics and biomarkers of TTR-aggregation-associated polyneuropathy and cardiomyopathy. This is especially true in the context of clinical trials demonstrating significant disease modifying effects, e.g. when the TTR tetramer stabilizer tafamidis was administered to familial amyloid polyneuropathy (FAP) patients early in the disease course. When asked if the findings of the tafamidis registration trial were sufficiently robust to provide substantial evidence of efficacy for a surrogate endpoint that is reasonably likely to predict a clinical benefit the advisory committee said yes, but the FDA rejected the tetramer stabilization surrogate biomarker required for orphan tafamidis approvalhence, acceptable biomarkers are badly needed. Herein, we explored whether peripheral blood cell mRNA expression profiles could differentiate symptomatic from asymptomatic V30M FAP patients, and if such a profile would normalize upon tafamidis treatment. We demonstrate that blood cell gene expression patterns reveal sex-independent as well as male and female specific inflammatory signatures in symptomatic FAP patients, but not in asymptomatic carriers, that normalize in FAP patients 6 months after tafamidis treatment. Thus these signatures have potential both as an early diagnostic and as a surrogate biomarker for measuring response to treatment in FAP patients.
Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures.
Age, Specimen part
View SamplesPrenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We analyzed transcriptome-wide gene expression profiles of 149 UCB samples from neonates born to mothers with prenatal PTSD (n=20), depression (n=31) and PTSD with comorbid depression (PTSD/Dep; n=13), compared to neonates born to carefully matched trauma exposed controls without meeting PTSD criteria (TE; n=23) and healthy mothers (n=62). We also evaluated physiological and developmental measures in these infants at birth, six months and twenty-four months. A multistep analytic approach was used that specifically sought to: 1) identify dysregulated genes, molecular pathways and discrete groups of co-regulated gene modules in UCB associated with prenatal maternal psychopathologies; and 2) to determine the impact of perinatal PTSD and depression on early childhood development outcomes.
Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes.
Specimen part
View SamplesDocetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment.
Identification of docetaxel resistance genes in castration-resistant prostate cancer.
Disease, Disease stage, Cell line, Treatment
View SamplesIMR-32 cells were subjected to lentiviral YRNA infection or nELAVL RNAi and/or UV stress followed by RNAseq analysis to monitor RNA level changes Overall design: RNA from IMR-32 cells was Trizol extracted, Ribominus selected and submitted for high-throughput sequencing.
Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain.
No sample metadata fields
View SamplesWe found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. We observed that the deletion of exon 8 in 10 male rats within the medial prefrontal cortex (mPFC) led to transcriptional alterations compared to 12 WT rats using RNAseq. Additionally, we used weighted gene co-expression network analysis to generate 23 modules specific to the mPFC with tissue from 35 WT rat samples. Overall design: RNAseq using WT and Fmr1 delta exon 8 mPFC samples
Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats.
Age, Specimen part, Cell line, Subject
View SamplesAlzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration as a result of abnormal neuronal loss. To elucidate the molecular systems associated with AD, we characterized the gene expression changes associated with multiple clinical and neuropathological traits in 1,053 postmortem brain samples across 19 brain regions from 125 persons dying with varying severities of dementia and variable AD-neuropathology severities.
Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer's disease.
Sex, Age, Specimen part, Race, Subject
View Samples