Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection, gradually cleared by host immunity
Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity.
Sex, Specimen part
View SamplesHepatoblastoma (HB) is the most common pediatric liver tumor, and there are no targeted therapies available for children with HB. We have previously developed a murine model of HB which is driven by coactivation of the oncogenes YAP1 and -catenin (CTNNB1) [Tao J, Calvisi D, Ranganathan S, et al. Gastroenterology, 2014 Sep; 147(3): 690701]. We used the Sleeping Beauty transposase system combined with hydrodynamic tail vein injection to deliver plasmids containing mutant activated forms of YAP1 (YAP S127A) and -catenin (N90 -catenin) to a small number of pericentral hepatocytes. We have shown that these few transformed hepatocytes proliferate and dedifferentiate, eventually forming histologically heterogeneous tumors that resemble various subtypes of human HB (which is also highly heterogeneous), including areas of well-differentiated fetal, crowded fetal, embryonal, and blastemal HB. Our goal was to investigate how coactivation of YAP1 and -catenin drive the dedifferentiation of hepatocytes into hepatoblast-like tumor cells over time, leading to HB tumors. In order to measure changes in gene expression during tumorigenesis in our model, we used an Affymetrix microarray to analyze isolated RNA from wild type FVB mouse livers, mouse HB tumor tissue, and non-tumor liver tissue adjacent to HB tumors.
Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.
Age, Specimen part
View SamplesLocated in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all other liver cell types by physical association and / or by producing cytokines and chemokines. In liver disease and folllowing liver transplantation, elevated levels of endotoxin (bacterial lipopolysaccharide: LPS) stimulate HSCs to produce increased amounts of cytokines and chemokines. Transcriptomic analysis of cultured HSCs stimulated with LPS yields a survey of expression changes which potentially modulate the hepatic inflammatory and immune responses.
The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.
Sex, Specimen part
View SamplesConditional disruption of Klf4 in the ectoderm-derived tissues of the eye results in defective cornea, conjunctiva and the lens.
Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4.
Specimen part
View SamplesThe bacterium Serratia marcescens is a common contaminant of contact lens cases and lenses. Serratamolide is one of the secreted hemolytic/cytotoxic factors which contribute to the virulence of this opportunistic pathogen (PMID 22615766).
No associated publication
Specimen part
View SamplesNeuronal reactivation of latent varicella zoster virus (VZV) causes debilitating and protracted pain (post herpetic neuralgia: PHN) in a significant fraction of patients.
Neuronal changes induced by Varicella Zoster Virus in a rat model of postherpetic neuralgia.
Sex
View SamplesDendritic cells (DCs) regulate both innate and adaptive immune responses.
Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea.
Specimen part
View SamplesOcular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)- and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFN, FasL and CD8+ T cells but not perforin or TNF were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFN and FasL did not target tumor cells directly as the majority of SPLNX IFNR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNR1. Bone marrow chimeras showed that immune cell expression of IFNR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFN- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFN- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
Splenectomy promotes indirect elimination of intraocular tumors by CD8+ T cells that is associated with IFNγ- and Fas/FasL-dependent activation of intratumoral macrophages.
Specimen part, Treatment
View SamplesDespite the documented benefits of breastfeeding and major governmental advocacy efforts, a paucity of data exists regarding the transfer of most drugs into breast milk. Passive diffusion governs the extent of accumulation for most drugs and the exposure risk can therefore be predicted using mathematical models. However, examples of xenobiotic accumulation into breast milk well above that predicted by passive diffusion have been documented and attributed to drug transport. A thorough evaluation of the expression of xenobiotic transporters in mammary epithelial cells (MECs), the cells that form the anatomical barrier between maternal serum and breastmilk, during lactation is necessary to determine the drugs for which an active transport mechanism governs transfer into breast milk and to improve predictive models.
No associated publication
Age, Specimen part, Disease
View SamplesWith aging, significant changes in circadian rhythms occur, including a shift in phase toward a morning chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmanns areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.
Effects of aging on circadian patterns of gene expression in the human prefrontal cortex.
Sex, Age, Specimen part, Race
View Samples