Reduced eukaryotic Initiation Factor 2 (eIF2)a phosphorylation (p-eIF2a) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2a has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2a in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2a in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ?FosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2a and the gateway drug properties of psychoactive cannabinoids. Overall design: RNAseq from PC12 cell line with a 6 hour DMSO or WIN treatment.
Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.
No sample metadata fields
View SamplesIn order to characterize defense responses not only cytologically, but also on the transcript level, genome-wide sequencing of mRNA isolated from non-infected control leaves and from leaves inoculated either with the WT or with GLS1 overexpressing strains was performed, using Illumina Next Generation Sequencing Technology. In order to identify transcripts specifically induced in leaves infected by ß-1,3-glucan-exposing strains, transcript patterns of leaves inoculated with GLS1 overexpressing PtrpC:GLS1 strains were compared with those of the WT. In PtrpC:GLS1-inoculated leaves, a total of 2179 genes were more than 2.5-fold increased, with many genes known as genes typically up-regulated in PAMP-triggered defense responses. These genes include genes encoding PR proteins enzymes involved in cell wall re-inforcemen, and terpene synthases possibly involved in phytoalexin synthesis. Furthermore, increased transcript abundance of genes encoding serine-threonine receptor-like kinases calmodulin, as well as zinc-finger and WRKY transcription factors have been identified. Other up-regulated genes encode proteins involved in protein degradation, i.e. proteases, ubiquitin ligases, as well as enzymes involved in synthesis of auxin or cytokinin phytohormones. In comparison, 2164 genes were more than 2.5-fold down-regulated in maize leaves infected by PtrpC:GLS1 strains, as compared to WT-infected leaves. Several of the encoded proteins are known susceptibility factors. Forty-six down-regulated genes code for proteins containing iron or manganese, or are involved in uptake of these ions, suggesting major re-arrangement of the redox-status in maize leaves after ß-glucan perception. Overall design: Examination of plant defense responses in maize plants inoculated with 2 different Colletotrichum graminicola strains.
Infection structure-specific expression of β-1,3-glucan synthase is essential for pathogenicity of Colletotrichum graminicola and evasion of β-glucan-triggered immunity in maize.
Age, Subject, Time
View SamplesBackground: In multiple sclerosis (MS), immune up-regulation is coupled to subnormal immune response to interferon-β (IFN-β) and low serum IFN-β levels. The relationship between the defect in IFN signalling and acute and long-term effects of IFN-β on gene expression in MS is inadequately understood. Methods: We profiled IFN-β-induced transcriptome shifts, using high-resolution microarrays on 227 mononuclear cell samples from IFN-β-treated MS Complete Responders (CR) stable for five years, and stable and active Partial Responders (PR), stable and active untreated MS, and healthy controls. Findings: IFN-β injection induced short-term changes in 1,200 genes compared to baseline expression after 4-day IFN washout. Pre-injection after washout, and in response to IFN-β injections, PR more frequently had abnormal gene expression than CR. Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes (ILT, IDO1, PD-L1). Expression of 8,800 genes was dysregulated n therapy-naïve compared to IFN-β-treated patients. These long-term changes in protein-coding and long non-coding RNAs affect immunity, synaptic transmission, and CNS cell survival, and correct the disordered therapy-naïve transcriptome to near-normal. In keeping with its impact on clinical course and brain repair in MS, long-term IFN-β treatment reversed the overexpression of proinflammatory and MMP genes, while enhancing genes involved in the oligodendroglia-protective integrated stress response, neuroprotection, and immunoregulation. In the rectified long-term signature, 277 transcripts differed between stable PR and CR patients.
Interferon-β corrects massive gene dysregulation in multiple sclerosis: Short-term and long-term effects on immune regulation and neuroprotection.
Age, Specimen part
View SamplesMYC is induced early in human adipose stem cells in response to a standard MDIR adipogenic cocktail. The objective of this experiment was to identify key gene networks impacted by MYC loss-of-function in a mixed donor pool of human derived adipose stem cells.
MYC is an early response regulator of human adipogenesis in adipose stem cells.
Sex, Race
View SamplesProjection-dependent ribosome profling from mouse mPFC.
Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.
Specimen part
View SamplesWe FACS-isolated single thirst-associated neurons from the median preoptic hypothalamus of mice and determined their individual transcriptomes. This characterization revealed a molecularly distinct population of excitatory thirst-associated neurons that is responsible for producing thirst motivational dirve. Overall design: Thirst-associated cells in the preoptic hypothalamus of mice were labeled using the Fos-p2A-CreER; Ai14 reporter mouse after 48 hour water deprivation. The preoptic hypothalamus was dissociated, and individual tdTomato+ cells were sorted into 96 well plates with lysis buffer. The transcriptomes of 570 putative cells were amplified using SmartSeq2 single-cell RNA-seq (Picelli et al., 2014). Libraries were prepared using an Illumina Nextera XT following Illumina''s protocols, and sequenced on an Illumina NextSeq 500. Data were processed using RSEM, and mapping directly to the ENSEMBL transcriptome, and quantified at a per-transcript level in TPM units. FASTQ files containing few reads (<1 MB in size for first paired-end read) were not mapped or subsequently analyzed; final dataset comprises 505 cells.
Thirst-associated preoptic neurons encode an aversive motivational drive.
Specimen part, Cell line, Subject
View SamplesWe aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.
Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesThe hemibiotrophic fungal pathogen Colletotrichum graminicola is the causal agent of anthracnose disease on maize stalks and leaves. After the formation of appressoria the host cell wall is penetrated by the conversion of appressorial turgor pressure into forceful ejection of a penetration peg. Subsequently, C. graminicola establishes biotrophic hyphae in the penetrated epidermis cell at around 36 hours post inoculation (hpi) until a switch of hyphal morphology and lifestyle takes place during the colonization of neighboring host cells at around 72 hpi. During the ensuing necrotrophic growth, dark necrotic lesions are formed that are visible as anthracnose symptoms. We used microarrays to detail the global programme of gene expression during the infection process of Colletotrichum graminicola in its host plant to get insight into the defense response of this compatible interaction and into the metabolic reprogramming needed to supply the fungus with nutrients.
Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens are not Based on Similar Transcriptional Reprogramming.
Time
View SamplesWe used FACS isolated RD cone photoreceptors from C3H mice (we refer this mouse model as f-RD) that were transfected by AAVs to express fluorescent reporters to genomic analyses. We tested three different ages.
Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa.
Age, Specimen part, Treatment
View Samplesmicrarray profiling on Arabidopsis thaliana col-0, cry1 and hfr1 in response to dark and 1 h blue light treatment
HFR1 is crucial for transcriptome regulation in the cryptochrome 1-mediated early response to blue light in Arabidopsis thaliana.
No sample metadata fields
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