Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
No sample metadata fields
View SamplesStaphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .
A TSLP-complement axis mediates neutrophil killing of methicillin-resistant <i>Staphylococcus aureus</i>.
No sample metadata fields
View SamplesUsing a mimic miR-200c was restored to an aggressive, Type 2 endometrial cancer cell line, Hec50
MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents.
Specimen part, Cell line
View SamplesNrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer.
Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO-methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis.
Sex, Specimen part
View SamplesTo identify signature genes associated with increased osteoblastic phenotype in response to co-culture of mesenchymal and neuroblastoma cells
Interaction between bone marrow stromal cells and neuroblastoma cells leads to a VEGFA-mediated osteoblastogenesis.
No sample metadata fields
View SamplesWe have generated over 80 million 32 nt reads generated from RNA samples isolated from the tip and base of a developing Mo17 leaf. A comparision of these data with the maize AGP resulted in the confirmation of approximately 88% of the maize filtered gene set Keywords: Transcriptome analysis Overall design: Examination of two different RNA samples from two different segments of a developing 3rd leaf
The B73 maize genome: complexity, diversity, and dynamics.
Specimen part, Subject
View SamplesAll above ground organs of higher plants are ultimately derived from shoot apical meristems (SAMs). The SAM exhibits distinctive structural organization, and monocot SAMs such as maize are comprised of two cell layers, a single cell layered tunica (L1) and a corpus (L2). Although recent research has revealed roles of these cell layers in the SAM, intra- and inter-cell-layer signaling networks involved in organ development remain largely unknown except for a few differentially expressed genes. Here, we used Illumnia technology to conduct RNA-seq of L1 and L2 cell layers in maize B73 maize shoot apical meristem. Overall design: Single sequencing library was constructed for L1 and L2 cell layer. Each library was sequenced using 2 lanes on a Solexa flow cell. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Subject
View SamplesHeterosis (hybrid vigor) refers to the superior performance of hybrid progeny relative to their parents. Although widely exploited in agriculture, the mechanisms responsible for heterosis are not well understood. As a monoecious organism, a given maize plant can be used as both male and female parents of crosses. Regardless of the cross direction, the maize inbred lines B73 and Mo17 produce hybrids that substantially out-perform their parents. These reciprocal hybrids differ phenotypically from each other despite having identical nuclear genomes. Consistent with these phenotypic observations, 30-50% of genes were differentially expressed between these reciprocal hybrids. An eQTL experiment conducted to better understand the regulation of gene expression in inbred and hybrid lines detected ~4,000 eQTL associations. The majority of these eQTL act in trans to regulate expression of genes on other chromosomes. Surprisingly, many of the trans-eQTL, when heterozygous, differentially regulated transcript accumulation in a manner consistent with gene expression in the hybrid being regulated exclusively by the paternally transmitted allele. The design of the eQTL experiment controlled for cytoplasmic and maternal effects, suggesting that widespread paternal genomic imprinting contributes to the regulation of gene expression in maize hybrids. Keywords: eQTL, parent-of-origin Overall design: GPL4521 - SAM1.2 (Reciprocal Hybrid Comparison): Six replications of B73xMo17 and Mo17xB73 were grown in growth chambers to tightly control environmental variation. Seeds from each genotype were taken from a single source (ear) for all six replications. Within each replication, genotypes were randomly assigned growth locations. Six healthy seedlings for each genotype and replication were harvested at two weeks of age. For each replication, B73xMo17 and Mo17xB73 were hybridized to the SAM1.2 microarray (GPL4521) using a randomized, alternate dye assignment. GPL3333 - SAM1.1 and GPL3538 - SAM3.0 (eQTL Experiment): Four biological replications of the RIL, B73xRIL, and Mo17xRIL cross-types were planted in growth chambers using seed from a single source for each genotype. Each RIL and its crosses onto B73 and Mo17 were planted using a split-plot design with RIL group (RIL and its cross onto B73 and Mo17) as the whole-plot treatment factor and cross-type (RIL, B73xRIL, and Mo17xRIL) as the split-plot treatment factor. The whole-plot portion of the experiment was designed as a randomized complete block design with four replications carried out on four separate occasions in the same environment. For the split-plot portion of the design, twelve seedlings of each RIL and its crosses were randomized within two adjacent flats in a growth chamber (six healthy seedlings per genotype were randomly chosen and pooled at harvest). For each replication, RIL, B73xRIL, and Mo17xRIL cross-types were hybridized to custom cDNA microarrays using a loop design such that each loop included all pairwise comparisons between the RIL and its crosses with B73 and Mo17. Four biological replications were hybridized to the SAM1.1 (GPL3333) array and two of the four biological replications were hybridized to SAM3.0 (GPL3538). RNA samples were alternately labeled to provide dye balance within each loop and replication. GPL8734 - Gene Expression between two maize reciprocal hybrids Heterosis refers to the enhanced agronomic performance of a hybrid relative to its (usually) inbred parents. We have previously documented widespread differences in gene expression in the B73xMo17 hybrid relative to its inbred parents B73 and Mo17 (Swanson, et al., 2006, PNAS). The reciprocal B73xMo17 and Mo17xB73 hybrids are both highly heterotic, but despite having identical nuclear genomes exhibit statistically significant differences in multiple traits. RNA-seq experiment was conducted to compare the gene expression globally between the two reciprocal hybrids. 1 samples from B73XMo17 and Mo17XB73 RNAs were extracted from a single replication of 14-day-old B73xMo17 and Mo17xB73 seedlings. RNAs were purified using DNaseI treatment followed by cleanup with the RNeasy Plant Mini Kit (Qiagen, Valencia, CA) as per manufacturer instructions. Sequencing library construction was completed using the Illumina mRNA-Seq sample preparation kit. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Specimen part
View SamplesTo compare hepatic gene expression in conditional Keap1 knockout (Alb-Cre:Keap1(flox/-)) and genetic control mice. Disruption of Keap1-mediated repression of Nrf2 signaling was expected to result in increased expression of Nrf2-regulated genes.
Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice.
No sample metadata fields
View SamplesPancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients.
CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer.
Sex, Specimen part, Treatment
View Samples