Mycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles.
Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
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View SamplesOvarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the p53 signature, or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells, but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes in pro-migratory genes in p53R273H MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53R273H with KRASG12V activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53R273H in the fallopian tube will improve understanding of changes at the earliest stage of transformation and could help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the p53 signature thereby, improving survival rates.
Mutant p53 expression in fallopian tube epithelium drives cell migration.
Specimen part
View SamplesPrevious work has suggested that the imprinted gene Phlda2 regulates the signalling function of the placenta by modulating the size of the endocrine compartment. This study investigated the affect that Phlda2 mutant placenta has upon the brains of the wildtype dams carrying different placenta and consequently offspring.
Maternal care boosted by paternal imprinting in mammals.
Specimen part
View SamplesWe developed an affinity purification approach to isolate tagged nuclei in mice (similar to INTACT; [Deal R.B. and Henikoff S. A simple method for gene expression and chromatin profiling of individual cell types within a tissue. Dev. Cell 18,1030-1040. (2010)]) and used it to characterize genome-wide patterns of transcription, DNA methylation, and chromatin accessibility in 3 major neuron classes of the neocortex (excitatory pyramidal neurons, parvalbumin (PV)-positive GABAergic interneurons, and vasoactive intestinal peptide (VIP)-positive GABAergic interneurons). By combining cell purification and integrative analysis, our findings relate the phenotypic and functional complexity of neocortical neurons to their underlying transcriptional and epigenetic diversity. Overall design: RNA-seq, MethylC-seq, ATAC-seq, and ChIP-seq for histone modifications using INTACT-purified nuclei from the mouse neocortex
Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesGLP-1 agonists are potent glucose-lowering agents, however, their effect on adolescent organisms needs to be clarified
Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition.
Age, Specimen part, Treatment
View SamplesHepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays.
Thyroid hormone-related regulation of gene expression in human fatty liver.
Sex, Age
View SamplesPsoriasin (S100A7) has been shown to be highly expressed in invasive estrogen receptor negative breast cancers. Expression of S100A7 in human breast tumors represents a poor prognostic marker and correlates with lymphocyte infiltration in high-grade morphology. Recent studies have shown that S100A7 downregulation in ER- cells lines inhibits tumor growth in in vivo mouse model systems. However, not much is known about its mechanisms in regulating breast cancers.
S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways.
Cell line
View Samples