Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Specimen part, Treatment, Time
View SamplesGlobal gene expressions of Mtb-infected mouse lungs were compared between with and without PDE4 inhibitor treatment. A lot of host genes are differentially expressed 21d and 28d post-Mtb infection. PDE4 inhibitor, however, downregulate 10% of genes among those and genes differentially regulated by PDE4 inhibitor are mainly involved immune response.
Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice.
Specimen part, Disease, Disease stage
View SamplesThe dual bromodomain protein Brd2 is closely related to the basal transcription factor TAFII250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.
Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis.
Specimen part
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesTranscriptomic profiling of human breast tumors.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Age, Specimen part
View SamplesBone morphogenic proteins (BMPs) function in virtually all tissues with cell-type specific outcomes. Since there are a relatively small number of BMP receptors this exquisite signaling specificity requires additional molecules to regulate the output of this pathway. We demonstrated that the receptor tyrosine kinase MuSK that is selectively expressed in muscle and plays a critical role in synapse formation and maintenance binds to BMP4 and related BMPs. Since BMPs regulate the transcription of a set of genes, we performed microarrays for wild-type and MuSK null muscle cells to test if MuSK regulates BMP responses in muscle cells.
MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells.
No sample metadata fields
View SamplesLiver gene expression was examined in male cynomolgus monkeys treated with ciprofibrate (PPAR-alpha agonist) for 4 days at 400 mg/kg/day and treated for 15 days at 0, 3, 30, 150 or 400 mg/kg/day. The untreated control group were given only the vehicle (0.5% hydroxypropyl methylcellulose). Two animals per group were used for the 4 day treatment and four animals per group were used for the 15 day treatment (except the 15 day control group, which had three animals). Selection of significantly changed probesets was done using Rosetta Resolver and the fold-change and p values as determined by Resolver are given below. Affymetrix CEL files and MAS5-processed data have been made availabe for convenience. Note that data processing reported in the Toxicological Sciences manuscript was done using Rosetta Resolver and the treated versus control group fold-change and p-value are appended to the Series entry. An article has been published in Toxicological Sciences regarding this dataset; the data interpretation was based on the Rosetta Resolver data.
Gene expression profiling of the PPAR-alpha agonist ciprofibrate in the cynomolgus monkey liver.
No sample metadata fields
View SamplesA multitude of genes have been associated with bipolar disorder via SNP genotyping studies. However, many of these associated SNPs are found within intronic or intergenic regions of the human genome. We were interested in studying transcriptional profiles/splice variation of genes associated with bipolar disorder within the human striatum. Understanding how these associated genes are transcribed in the human brain may help to guide the development of therapeutic agents for the treatment of bipolar disorder and other neuropsychiatric illnesses. Overall design: NEBNext Ultra Directional RNAseq libraries were generated from putamen and caudate nucleus tissues from 4 healthy control individuals and 4 individuals with bipolar disorder. These libraries were then multiplexed and run on an Illumina HiSeq platform using single read 100bp chemistries.
Novel PDE10A transcript diversity in the human striatum: Insights into gene complexity, conservation and regulation.
Specimen part, Disease stage, Subject
View SamplesSkin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development.
Chromatin effector Pygo2 mediates Wnt-notch crosstalk to suppress luminal/alveolar potential of mammary stem and basal cells.
Specimen part
View Samples