Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide and causes respiratory disease, abortion, and in some cases, neurological disease.EHV-1strain KyA is attenuated in the mouse and equine, whereaswild-typestrain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb at 4 to 6 days post-infection. Our previous results showed that EHV-1 KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks post-immunization, and that the infection with theattenuatedKyA elicits protective humoral and cell-mediated immune responses.To investigate the protective mechanisms of EHV-1 KyA by innate immune responses, CBA mice immunized with live KyA were challenged with RacL11 at various timespost-vaccination. KyA immunization effectively protected CBA mice from RacL11 challenge at 1 to 7 dayspost-immunization. Immunized mice lost less than 10% of their preinfection body weight and rapidly regained body weight. Lung virus titers in EHV-1 KyA-immunized CBA mice were 1,000-fold lower at 2 days post-RacL11 challenge than lungs of non-immunized mice, which was indicative of accelerated virus clearance. Affymetrix microarray analysis revealed thatIFN-and16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h post-challengein the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-inhibitedEHV-1 infection of murine alveolar macrophage MH-S cells andeffectively protected mice against lethal EHV-1 challenge, suggesting that IFN-expression may be important in mediating protection elicited by KyA immunization. These results suggestthat EHV-1 KyA can be used asa live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.
Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge.
Sex, Specimen part
View SamplesAcquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000 fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors.
Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors.
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View SamplesHuman papillomaviruses (HPVs) target PML nuclear bodies during infectious entry and PML protein is important for efficient transcription of incoming viral genome.We used shRNA to knockdown PML protein in HaCaT keratinocytes to further investigate the role of PML protein in HPV entry.
No associated publication
Specimen part, Cell line
View SamplesGene expression along the crypt-villus (C-V) axis was analyzed using cryostat sectioning to isolate fractions representing the crypts (bottom) and villus tops (top). These fractions were used for analyzing gene expression in iron replete Wistar rats (++), iron deficient Wistar rats (low iron), and in iron deficient Wistar rats fed iron for 3 and 6 days (iron-fed). Differences were observed between the crypts and villus tops in the expression of genes associated with Wnt and BNP signaling, cell proliferation and apoptosis, lipid and iron transport and metabolism. Gene expression in villus crypts and tops was also compared between Wistar and Belgrade rats (bb) and Belgrade rats fed iron (iron-fed) particularly as related to iron absorption and metabolism to define the affects of the mutation in DMT1 in the Belgrade rat on the expression of genes related to iron absorption and metabolism and the response to iron feeding.
Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine.
No sample metadata fields
View SamplesAnalysis of effects of A scoparia on gene expression in adipose tissue. Current study was designed to examine the whole-body and tissue-specific effects of A scoparia on metabolic parameters in the context of high-fat diet-induced obesity and insulin resistance.
No associated publication
Sex, Specimen part
View SamplesPAPER 1:"Identification of novel subgroups of high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL) by unsupervised microarray analysis: clinical correlates and therapeutic implications. A Children's Oncology Group (COG) study."
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
Sex, Specimen part, Race
View SamplesThe lung is the entry site for Bacillus anthracis in inhalation anthrax, the most deadly form of the disease. Spores must escape through the alveolar epithelial cell (AEC) barrier and migrate to regional lymph nodes, germinate and enter the circulatory system to cause disease. Several mechanisms to explain alveolar escape have been postulated, and all these tacitly involve the AEC barrier. In this study, we incorporate our primary human type I AEC model, microarray gene profiling and gene enrichment analysis to study the response of AEC to B. anthracis, (Sterne) spores at 4 and 24 hours post-exposure. Spore exposure altered gene expression in AEC after 4 and 24 hours and differentially expressed genes (1.3 fold, p 0.05) included CCL4/MIP-1 (4 hours), CXCL8/IL-8 (4 and 24 hours) and CXCL5/ENA-78 (24 hours). Gene enrichment analysis revealed that pathways involving cytokine or chemokine activity, receptor binding, and innate immune responses to infection were prominent. Microarray results were confirmed by qRT-PCR and multiplex ELISA assays. Chemotaxis assays demonstrated that spores induced the release of biologically active neutrophil and monocyte chemokines, and that CXCL8/IL-8 was the major neutrophil chemokine. The small or sub-chemotactic doses of CXCL5/ENA-78, CXCL3/GRO and CCL20/MIP-3 may contribute to chemotaxis by priming effects. These data provide the first whole transcriptomic description of the human type I AEC initial response to B. anthracis spore exposure, and contribute to an increased understanding of the role of AEC in the pathogenesis of inhalational anthrax.
No associated publication
Sex, Specimen part, Race, Subject
View SamplesComparison of Total RNA and Polysome-bound RNA populations in deltaTOR containing cells and control cells upon hepatocyitc differentiation.
Mammalian target of rapamycin activation impairs hepatocytic differentiation and targets genes moderating lipid homeostasis and hepatocellular growth.
Specimen part, Cell line
View SamplesComparison of transcriptional and translational regulation upon hepatocytic diffentiation by Total RNA and polysome bound RNA profiling.
Translational control plays a prominent role in the hepatocytic differentiation of HepaRG liver progenitor cells.
Sex, Age, Specimen part, Cell line, Time
View SamplesThe respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cels, that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systemically identify these subsets in human airways, by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting cells were consistently observed, which varied in their ability to internalize bacterial particles. Subsets could be further separated by their inherent capacities to upregulate CD83, CD86, and CCR7. Whole genome transcriptional profiling revealed a clade of true dendritic cells distinct from a macrophage/monocyte clade. Each clade, and each member of both clades, could be discerned by specific genes of increased expression, which would serve as markers for future studies in healthy and diseased states.
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
Sex, Age
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