Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.
Sex, Age, Specimen part, Treatment
View SamplesDystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1, a zinc-finger transcription factor, cause DYT6, but its neuronal targets and functions are unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1C54Y or ?Exon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2a Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic Long Term Depression pathways, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays confirmed the functional significance of those findings. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence on the pathogenesis of unrelated forms of inherited dystonia. Overall design: We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1C54Y or deltaExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum
Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.
Specimen part, Cell line, Subject
View SamplesThe budding yeast, Saccharomyces cerevisiae, has emerged as an archetype of eukaryotic cell biology. Here we show that S. cerevisiae is also a model for the evolution of cooperative behavior by revisiting flocculation, a self-adherence phenotype lacking in most laboratory strains. Expression of the gene FLO1 in the laboratory strain S288C restores flocculation, an altered physiological state, reminiscent of bacterial biofilms. Flocculation protects the FLO1-expressing cells from multiple stresses, including antimicrobials and ethanol. Furthermore, FLO1+ cells avoid exploitation by non-expressing flo1 cells by self/non-self recognition: FLO1+ cells preferentially stick to one another, regardless of genetic relatedness across the rest of the genome. Flocculation, therefore, is driven by one of a few known green beard genes, which direct cooperation towards other carriers of the same gene. Moreover, FLO1 is highly variable among strains both in expression and in sequence, suggesting that flocculation in S. cerevisiae is a dynamic, rapidly-evolving social trait.
FLO1 is a variable green beard gene that drives biofilm-like cooperation in budding yeast.
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View SamplesTranscriptional profiling after inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells
Transcriptional profiling in response to inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells.
Specimen part
View SamplesAbstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis.
Platelets and platelet-like particles mediate intercellular RNA transfer.
Specimen part, Cell line
View SamplesThe heterogeneity of cortical dopamine D2 receptor expressing cells is not well characterized
High Sensitivity Mapping of Cortical Dopamine D2 Receptor Expressing Neurons.
Specimen part
View SamplesThis study focused on transcription in the medial PFC (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized on tasks, attentional set shift and spatial memory, which depend on the mPFC and hippocampus, respectively. Differences in transcription associated with age and cognitive function were examined using RNA sequencing to construct transcriptomic profiles for the mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging associated with increased expression of immune and defense response genes and a decline in synaptic and neural activity genes. Importantly, we provide evidence for region specific transcription related to behavior. In particular, expression of transcriptional regulators and neural activity-related immediate-early genes (IEGs) are increased in the mPFC of aged animals that exhibit delayed set shift behavior; relative to age-matched animals that exhibit set shift behavior similar to younger animals. Overall design: The study contains 11 young and 20 aged rats for the mPFC and CA1 samples, which were used to investigate expression patterns associated with aging and behavior. White matter samples were used to investigate an age-related effect with 8 young and 9 aged rats.
Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex.
No sample metadata fields
View SamplesTo analyse and understand the differentially expressed genes following treatment with synthetic androgen (R1881) Overall design: LNCaP or LAPC4 cells were plated in RPMI 1640 media with no phenol red and with 5% charcoal stripped serum, sodium pyruvate, penicillin and streptomycin. After 48h (to allow adnrogen deprivation), fresh media was added, with 96% ethanol or the synthetic androgen R1881 (10nM concentration). 24h later, cells were harvested for RNA purification using the QIAGEN RNeasy plus purification kit. RNA was then enriched for mRNA and then sequenced.
RNA sequencing data of human prostate cancer cells treated with androgens.
Treatment, Subject
View SamplesWe identified DCIR2+DCs but not DEC205+DCs as able to induce peripheral T cell tolerance in pre-diabetic autoimmune NOD mice. To determine what distinct genetic programs are elicited in the auto-reactive CD4 T cells early after stimulation by these two DC subsets, we utilized adoptive transfer of BDC2.5 CD4 T cells into NOD mice, which were then given chimeric antibody to deliver the beta-cell specific antigen to either DCIR2+DCs or DEC205+DCs, leading to BDC2.5 CD4 T cell specific stimulation in vivo. The analysis shows that the negative transcriptional factor Zbtb32 (ROG) is up-regulated more in BDC2.5 CD4 T cells after stimulated with a antigen via DCIR2+DCs presentation, compared with DEC205+DCs, suggesting the involvement of Zbtb32 in DCIR2+DCs-mediated auto-reactive T cell tolerance in disease ongoing NOD mice.
DCIR2+ cDC2 DCs and Zbtb32 Restore CD4+ T-Cell Tolerance and Inhibit Diabetes.
Sex, Age, Specimen part
View SamplesThe prognosis of colorectal cancer (CRC) stage II and III patients is still a challenge due to the difficulties of finding robust biomarkers and assays. The majority of published gene signatures of CRC have been generated on frozen colorectal tissues. Because collection of fresh frozen tissues is not routine and the quantity and quality of RNA derived from formalin-fixed paraffin-embedded (FFPE) tissues is vastly inferior to that derived from fresh frozen tissue, a clinical test for improving staging of colon cancer will need to be designed for FFPE tissues in order to be widely applicable. We have designed a custom Nanostring nCounter assay for quantitative assessment of expression of 414 gene elements consisting of multiple published gene signatures for colon cancer prognosis, and systematically compared the gene expression quantification between nCounter data from FFPE and Affymetrix microarray array data from matched frozen tissues using 414 genes.
Comparison of Nanostring nCounter® Data on FFPE Colon Cancer Samples and Affymetrix Microarray Data on Matched Frozen Tissues.
Disease
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