Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein (HSD) or that has been supplemented with a rich source of saturated fat (HFD). These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline, such as decreased climbing ability. We subjected Oregon-R-C flies to variants of the HSD, HFD, or normal (control) diet (ND), followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. We targeted at least 50 million paired-end, stranded reads of 75 basepairs in size, and analyzed 4 biological replicates per dietary condition. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Functional annotation and enrichment analysis among genes whose expression was significantly affected by the obesogenic diets indicated an overrepresentation of genes associated with immunity, metabolism, and hemocyanin in the HFD group, and CHK, cell cycle activity, and DNA binding and transcription in the HSD group. Heat map representation of genes affected by both diets illustrated a large fraction of differentially expressed genes between the two diet groups. Diets high in sugar and diets high in fat both have notableeffects on the Drosophila transcriptome in head tissue. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation. Our results also indicate differences in the effects of the HFD and HSD on expression profiles in head tissue of Oregon-R-C flies, despite the reportedly similar phenotypic impacts of the diets. Overall design: Flies were reared on one of three diets (high fat, high sugar, or normal). 6 replicates, with twenty flies each, from each diet treatment were collected for a total of 18 samples. The heads of the flies were then obtained, and RNA extracted from each of those samples. 4 of the RNA samples from each diet group (12 samples total) were sequenced.
RNA-Sequencing of <i>Drosophila melanogaster</i> Head Tissue on High-Sugar and High-Fat Diets.
Specimen part, Subject
View SamplesThe transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis, suggestive of a progesterone resistant endometrium in this disease.
Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.
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View SamplesHuman oviduct serves as a conduit for sperm in the peri-ovulatory phase and to nurture and facilitate transport of the developing embryo en route to the uterus for subsequent nidation during the luteal phase of the cycle. Interactions between the embryo and oviductal epithelial surface proteins and secreted products during the four day embryo transit are largely undefined. Herein, we have investigated gene expression in human oviduct in the early luteal vs. follicular phase to identify candidate genes and biomolecular processes that may participate in maturation and transport of the embryo as it traverses this tissue. Oviductal RNA was isolated, processed, and hybridized to oligonucleotide arrays. Resulting data were analyzed by bioinformatic approaches and revealed that 650 genes were significantly downregulated and 683 genes were significantly upregulated in the luteal vs. follicular phase. Real-time RT-PCR, immunoblot analysis, and immunohistochemistry confirmed select gene expression and cellular protein localization. The data demonstrate downregulation of genes involved in macrophage recruitment, immunomodulation, and matrix-degeneration and upregulation of ion transport and secretions as well as anti-angiogenic and early pregnancy recognition genes in luteal vs. follicular phase oviduct. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through human oviduct.
The human oviduct transcriptome reveals an anti-inflammatory, anti-angiogenic, secretory and matrix-stable environment during embryo transit.
Specimen part
View SamplesTo examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Age
View SamplesDuring the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions.
Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators.
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View SamplesThe outcome of infections with Toxoplasma gondii in humans is dependent in part on the genetic makeup of the infecting organism. Recent studies have indicated that most infecting Toxoplasma organisms fall into 1 of 3 canonical lineages. Previous studies have investigated the effects of Toxoplasma on its host cell transcriptome. Little is known, however, about the effects of three canonical lineages on brain cells, the principal site of parasite lifelong persistence. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to T. gondii infection using microarray analysis to characterize the strain-specific host cell response to 3 canonical T. gondii strains. We found that the extent of the expression changes varied considerably among the three strains. Neuroepithelial cells infected with type I exhibited the most differential gene expression, whereas type II infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to central nervous system while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter expression of a clearly defined set of genes. Moreover, Ingenuity pathway analysis (IPA) revealed the sophistication of different strain in its interactions with the host. These differences may explain some of the variation in the neurobiological effects of different strains of Toxoplasma on infected individuals.
Differential effects of three canonical Toxoplasma strains on gene expression in human neuroepithelial cells.
Cell line
View SamplesWe look at differential gene expression between immortalized p65+/+ and p65-/- MEFs to identify potential NF-kB regulated genes which when grouped based on biological function indicates candidates involved in protecting p65+/+ cells from macrophage-mediated killing Overall design: Examination of differential gene expression between two cell types either in the presence or absence of p65
NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development.
Specimen part, Cell line, Subject
View SamplesTransactive response DNA-binding protein of 43 kDa (TDP-43), a heterogeneous nuclear ribonucleoprotein (hnRNP) with diverse activities, is a common denominator in several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Orthologs of TDP-43 exist from mammals to invertebrates, but their functions in lower organisms remain poorly understood. Here we systematically studied mutant Caenorhabditis elegans lacking the nematode TDP-43 ortholog, TDP-1. To understand the global gene expression regulation induced by the loss of tdp-1, the C. elegans transcriptomes were compared between the N2 WT animals and the tdp-1(ok803lf) mutant. Transcriptional profiling demonstrated that the loss of TDP-1 altered expression of genes functioning in RNA processing and protein folding. These results suggest that the C. elegans TDP-1 as an RNA-processing protein may have a role in the regulation of protein homeostasis and aging.
Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span.
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View SamplesThe mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection.
Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics.
No sample metadata fields
View SamplesComparison of wild type barley plants versus plants over-expressing ODDSOC2; a vernalization responsive MADS box gene ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Aaron Greenup. The equivalent experiment is BB93 at PLEXdb.]
ODDSOC2 is a MADS box floral repressor that is down-regulated by vernalization in temperate cereals.
Specimen part
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