In vertebrate muscle, loss of Dysferlin results in the activation of compensatory muscle gene expression, even at pre-pathological stages. We hypothesized that if C. elegans fer-1 is also expressed in muscle, then fer-1 mutant worms might also exhibit compensatory muscle gene expression.
C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.
Specimen part
View SamplesGlucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma - excessive ASM growth are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as interleukin 1beta and tumor necrosis factor alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and interleukin 1beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis.
Glucocorticoid- and protein kinase A-dependent transcriptome regulation in airway smooth muscle.
No sample metadata fields
View SamplesLymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
Infrequent loss of luminal differentiation in ductal breast cancer metastasis.
Specimen part
View SamplesUsing Affymetrix microarray technology we analyzed the gene expression profiles of the most important pathological categories of bladder cancer in order to detect potential marker genes. Applying an unsupervised cluster algorithm we observed clear differences between tumor and control samples, as well as between superficial and muscle invasive tumors. According to cluster results, the T1 high grade tumor type presented a global genetic profile which could not be distinguished from invasive cases. We described a new measure to classify differentially expressed genes and we compared it against the B-rank statistic as a standard method. According to this new classification method, the biological functions overrepresented in top differentially expressed genes when comparing tumor versus control samples were associated with growth, differentiation, immune system response, communication, cellular matrix and enzyme regulation. Comparing superficial versus invasive samples, the most important overrepresented biological category was growth and, specifically, DNA synthesis and mitotic cytoskeleton. On the other hand, some under expressed genes have been clearly related to muscular tissue contamination in control samples. Finally, we demonstrated that a pool strategy could be a good option to detect the best differentially expressed genes between two compared conditions.
DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers.
No sample metadata fields
View SamplesIn the present study, the transcriptional analysis of CD biopsies reveals profound alterations in the ileum transportome profile. More than 60 SLC transporters showed different expression pattern compared with the healthy donors, being mostly decreased. Changes were confirmed in almost all the eighteen altered SLCs analyzed by RT-PCR. The results obtained display alterations in amino acid transporters, purinome members, Zn transporters and metallothioneins. All together, these alterations which mainly involve transporters localized at the apical membrane of the enterocyte anticipate impaired amino acid uptake and purinergic responses. Remarkably, incubation of explants with specific commensal bacteria restored almost all CD transportome alterations.
Transportome Profiling Identifies Profound Alterations in Crohn's Disease Partially Restored by Commensal Bacteria.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.
Specimen part, Cell line
View SamplesWe have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Specimen part, Subject
View SamplesWe have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Specimen part, Subject
View SamplesThe goal of the study was to understand whether mitochondrial-driven epigenetic changes regulate gene expression. Mitochondrial metabolism has been implicated in epigenetics but the extent to which this impacts gene expression is unclear. Here we show that loss of mitochondrial DNA (mtDNA) results in locus-specific alterations in histone acetylation, DNA methylation and expression of a subset of genes. Most of these changes are rescued by restoring mitochondrial electron transport in a way that maintains the oxidative tricarboxylic acid cycle, but not reactive oxygen species or ATP production, or by modulating the mitochondrial pool of acetyl-CoA. Changes in acetyl-CoA and histone acetylation precede overt mitochondrial dysfunction and significant changes in gene expression and DNA methylation. This suggests that acetyl-CoA levels signal mitochondrial status to the nucleus. Differentially expressed genes with altered histone marks or DNA methylation regulate amino acid degradation, which likely compensates for the changes in acetyl-CoA and one carbon metabolism. These have the potential to further affect methylation reactions, redox control and nucleotide levels. These results illustrate the extent to which mitochondria impact cell physiology through epigenetic remodeling.
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.
Cell line
View SamplesThe yeast PMR1 (ATP2C1) gene codes for the eukaryotic prototype of a high affinity P-type ATPase required for Ca2+/Mn2+ transport into the Golgi. Cells lacking PMR1 exhibit multiple genetic interactions with genes involved in DNA recombination and replication, a fact that is not yet understood. We find that deletion of PMR1 causes a delay in DNA replication initiation, progression and G2/M transition and induces the transcriptional up-regulation of genes involved in cell cycle regulation, including CLB5 and SWE1. Interestingly, pmr1 clb5 double mutants exhibit a dramatic delay in DNA replication and increased DNA breakage, while endoreplication and the formation of multi-nucleated, giant yeast is observed in pmr1 swe1 cells. Because these phenotypes can be attributed to impeded Mn2+-pump function, we provide a model in which Mn2+ interferes with Mg2+ in the nucleus, and vice versa, Mg2+ interferes with Mn2+ in the Golgi. Consequently, cell cycle progression is challenged by aberrant catalytic activities of enzymes involved in replication and protein glycosylation.
Impaired manganese metabolism causes mitotic misregulation.
No sample metadata fields
View Samples