Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out.
Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Specimen part
View SamplesTissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Specimen part
View SamplesMicroarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons
Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.
No sample metadata fields
View SamplesAged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines and increased production of interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS (169 in only the young, 184 in only the aged, and 500 in both). Expression analysis of systematic explorer revealed that immune response (proinflammatory chemokines, cytokines, and their receptors) and signal transduction genes were specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6 was reduced, and Il10 was increased, confirming our previous results. There was also decreased expression of interferon-gamma. Genes in the Toll-like receptor-signaling pathway leading to nuclear factor-kappaB activation were also down-regulated but IL-1 receptor-associated kinase 3, a negative regulator of this pathway, was increased in aged mice. An increase in expression of the gene for p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding increase in protein expression and enzyme activity confirmed by Western blotting. Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK activity has a role in cytokine dysregulation in the aged mouse Mphi.
Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages.
Specimen part
View SamplesMicroarray analysis of gene expression in the olfactory epithelium of macrophage depleted mice to study the role of macrophages in regulating neurodegeneration, neuroprotection, and neurogenesis of olfactory sensory neurons
Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium.
No sample metadata fields
View SamplesCTCF is an organizer of higher-order chromatin structure, and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, there is no knowledge of the role of CTCF-mediated chromatin structure in learning and memory. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization. Cognitive disabilities are associated with downregulation of cadherin and learning-related genes. In addition, CTCF knockdown attenuates fear conditioning-induced hippocampal gene expression of key learning genes and loss of long-range interactions at the BDNF and Arc loci. This study identifies CTCF-dependent gene expression regulation and DNA structure as regulators of learning and memory. Overall design: 3 biological replicates of wild type and 3 biological replicates of CTCF cko mice
Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc.
Specimen part, Cell line, Subject
View SamplesSkin squamous cell carcinomas are among the most frequent human cancers. In this study we compared the expression profiles of 10 skin SCCs with a set of 3 normal human epidermis controls.
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.
Disease, Disease stage
View SamplesTranscriptome analysis of human peripheral blood T cells
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sex, Specimen part, Time
View SamplesTranscriptome analysis of human peripheral blood monocytes
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sex, Specimen part, Subject, Time
View SamplesTo evaluate the transcriptomes of lesional skin from different body parts of the same individual. Specifically, we conducted a transcriptomic study to investigate expression variability for diseased samples taken from different anatomic regions of same patient, and to compare the variability to between individuals variability. Overall design: 5 psoriasis patients, each with 4 psoriatic and 1 uninvolved skin biopsies. Totally 25 RNA-seq experiments conducted.
Transcriptional determinants of individualized inflammatory responses at anatomically separate sites.
Specimen part, Disease stage, Subject
View Samples