To elucidate biological processes underlying the keratocyte, fibroblast, and myofibroblast phenotypes of corneal stromal cells, the gene expression patterns of these primary cultures from mouse cornea were compared with those of the adult and 10-day postnatal mouse cornea.
Microarray studies reveal macrophage-like function of stromal keratocytes in the cornea.
No sample metadata fields
View SamplesWe use the zebrafish embryo model to study the innate immune response against polystyrene particles. Therefore, we injected 700nm polystyrene into the yolk at 2 dpf and took samples at 1 and 3 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by polystyrene particle toxicity. RNA was isolated from embryos at 1 and 3 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2dpf) with 1nl of 5mg/ml of 700nm red fluorescent polystyrene particles suspended in PVP (Polyvinylpyrrolidone) (n=3), mock injected with pvp (n=2), or Non-injected as a control (n=3). After injections embryos were transferred into fresh egg water and incubated at 28°C. At 1 and 3 days post injection 10 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae.
No sample metadata fields
View SamplesCongenital heart defects (CHD) are one of the most common defects in offspring of diabetic mothers. There is a clear association between maternal diabetes and CHD; however the underlying molecular mechanism remains unknown. We hypothesized that maternal diabetes affects with the expression of early developmental genes that regulate the essential developmental processes of the heart, thereby resulting in the pathogenesis of CHD. We analyzed genome-wide expression profiling in the developing heart of embryos from diabetic and control mice by using the oligonucleotide microarray. Microarray analysis revealed that a total of 878 genes exhibited more than 1.5 fold changes in expression level in the hearts of experimental embryos in either E13.5 or E15.5 compared with their respective controls. Expression pattern of genes that is differentially expressed in the developing heart was further examined by the real-time reverse transcriptase-polymerase chain reaction. Several genes involved in a number of molecular signaling pathways such as apoptosis, proliferation, migration and differentiation in the developing heart were differentially expressed in embryos of diabetic pregnancy. It is concluded that altered expression of several genes involved in heart development may contribute to CHD in offspring of diabetic mothers.
Differential gene expression profiles during embryonic heart development in diabetic mice pregnancy.
Disease
View SamplesPro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-B dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-B activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-B target gene-expressions and suppressing apoptotic cellular death independent of principal NF-B subunit RelA. We further demonstrate that activating mutations in non-canonical NF-B module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-B response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-B system and its potential involvement in human neoplasm.
Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.
Specimen part, Treatment
View SamplesWhole transcript analysis of amyloid beta 42 (Aβ42)-induced SH-SY5Y cells in control and treated groups (curcumin, piperine and combination therapy) were assessed using microarray profiling. A number of up-regulated and down-regulated genes were altered in sample-specific group.
Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (A<i>β</i>) explicit pathway: recovery and reversal paradigm effects.
Sex, Specimen part, Cell line
View SamplesWest Nile virus (WNV) is the most important cause of endemic encephalitis in the USA. Strikingly, only a small percentage of patients develop clinical disease and of these patients, approximately 1 out of 150 patients develops encephalitis. The basis for this great variability in disease outcome is unknown, but may be related to the innate immune response. Innate immune responses, critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors (PRR) such as RIG-I and MDA5. IPS-1 is a key adaptor in generating a PRR-dependent interferon response.. Here we show that IPS-1 deficiency in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In IPS-1-/- mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were multifunctional and were able to lyse peptide-pulsed target cells in vitro. However, virus-specific T cells in the infected IPS-1-/- brain exhibited lower functional avidity than those in C57BL/6 brains, possibly contributing to less efficient virus clearance. The presence of virus-specific memory T cells was also not protective. We also show that macrophages were increased in numbers in the IPS-1-/- brain. Both macrophages and microglia exhibited an activated phenotype. Microarray analyses showed the preferential upregulation of genes associated with leukocyte activation and inflammation. Together, these results demonstrate the critical role that hematopoietic cell expression of Type 1 interferon and other IPS-1-dependent molecules have in WNV clearance and in regulating the inflammatory response.
MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.
Specimen part, Time
View SamplesCell type specific transcriptome analysis from laser microdissected megaspore mother cells (MMC) from Arabidopsis thaliana (L.) Heynh., accession Landsberg erecta.
Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the importance of RNA helicases for plant germline development.
Sex, Specimen part, Subject
View SamplesNucellus tissue surrounding the megaspore mother cell in Arabidopsis thaliana (L.) Heynh. , accession Landsberg erecta, isolated by laser assisted microdissection
Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the importance of RNA helicases for plant germline development.
Specimen part, Subject
View SamplesHepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation. As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1). In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice. Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs. In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy.
Molecular characterization of hepatocarcinogenesis using mouse models.
Specimen part
View SamplesThe primary objective of the study was to investigate the uncoupling protein-1 (UCP1) associated features of human epicardial adipose tissue (eAT) using next generation deep sequencing. In addition, paired mediastinal adipose tissue (mAT) and subcutaneous adipose tissue (sAT) samples colleced from patients undergoing cardic surgeries at our center were included in the study. Overall design: Paired biopsies of eAT, mAT and sAT obtained from cardiac surgery patients (n=10), with specific criteria of high- and low- expression of UCP1 in eAT, were subjected to RNA sequencing. While the primary objective was to compare high- vs. low UCP1 expression in eAT, our study design further allowed us to investigate depot- and disease specific transcriptomic shifts in these patients. Specifically, 10 patients provided 30 samples (n = 10 each for eAT, mAT and sAT) that could be compared based on depot specificity (n = 10), obesity (n = 5 lean, n = 5 obese) and coronary artery disease (CAD) (n = 6 CAD, 4 = Non-CAD).
UCP1 expression-associated gene signatures of human epicardial adipose tissue.
Disease, Disease stage, Subject
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