Evaluating a Rapid Field Assessment System for Anticoagulant Rodenticide Exposure of Raptors.

Anticoagulant rodenticides (ARs) are commonly used to control rodent pests. However, worldwide, their use is associated with secondary and tertiary poisoning of nontarget species, especially predatory and scavenging birds. No medical device can rapidly test for AR exposure of avian wildlife.

Center of Biomedical Research Excellence in Matrix Biology: Building Research Infrastructure, Supporting Young Researchers, and Fostering Collaboration.

The Center of Biomedical Research Excellence in Matrix Biology strives to improve our understanding of extracellular matrix at molecular, cellular, tissue, and organismal levels to generate new knowledge about pathophysiology, normal development, and regenerative medicine. The primary goals of the Center are to i) support junior investigators, ii) enhance the productivity of established scientists, iii) facilitate collaboration between both junior and established researchers, and iv) build biomedical research infrastructure that will support research relevant to cell-matrix interactions in disease progression, tissue repair and regeneration, and v) provide access to instrumentation and technical support. A Pilot Project program provides funding to investigators who propose applying their expertise to matrix biology questions.

Characterization of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease.

Background: Borrelia burgdorferi causes Lyme disease, the most common tick-borne illness in the United States. The Center for Disease Control and Prevention estimates that the occurrence of Lyme disease in the U.S.

Electronic cigarette liquid exposure induces flavor-dependent osteotoxicity and increases expression of a key bone marker, collagen type I.

Electronic cigarettes (e-cigarettes) are nicotine delivery devices advertised as a healthier alternative to conventional tobacco products, but their rapid rise in popularity outpaces research on potential health consequences. As conventional tobacco use is a risk factor for osteoporosis, this study examines whether exposure to electronic liquid (e-liquid) used in e-cigarettes affects bone-forming osteoblasts. Human MG-63 and Saos-2 osteoblast-like cells were treated for 48 hours with 0.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases necroinflammation and hepatic stellate cell activation but does not exacerbate experimental liver fibrosis in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Increasing evidence indicates that AhR signaling contributes to wound healing, which involves the coordinated deposition and remodeling of the extracellular matrix. In the liver, wound healing is attributed to the activation of hepatic stellate cells (HSCs), which mediate fibrogenesis through the production of soluble mediators and collagen type I.

Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis.

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl).

Monocyte chemoattractant protein-1 is not required for liver regeneration after partial hepatectomy.

Background: Liver regeneration following 70 % partial hepatectomy (PH) requires the coordinated expression of soluble mediators produced by macrophages. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulus of monocyte recruitment and macrophage activation. The goal of this study was to determine how MCP-1 contributes to liver regeneration.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver.

Ah receptor-mediated suppression of liver regeneration through NC-XRE-driven p21Cip1 expression.

Previous studies in hepatocyte-derived cell lines and the whole liver established that the aryl hydrocarbon receptor (AhR) can disrupt G1-phase cell cycle progression following exposure to persistent AhR agonists, such as TCDD (dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin). Growth arrest was attributed to inhibition of G1-phase cyclin-dependent kinase 2 (CDK2) activity. The present study examined the effect of TCDD exposure on liver regeneration following 70% partial hepatectomy in mice lacking the Cip/Kip inhibitors p21(Cip1) or p27(Kip1) responsible for regulating CDK2 activity.

Consequences of TCDD treatment on intra-hepatic lymphocytes during liver regeneration.

Increasing evidence demonstrates a physiological role for the aryl hydrocarbon receptor (AhR) in regulating hepatocyte cell cycle progression. Previous studies have used a murine model of liver regeneration to show that exposure to the potent exogenous AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), suppresses hepatocyte proliferation in vivo. Based on recent reports that natural killer (NK) cells negatively regulate liver regeneration, coupled with the well-established immunomodulatory effects of TCDD, it was hypothesized that alterations in lymphocyte activation contribute to the suppression of liver regeneration in TCDD-treated mice.

Regulation of hepatocyte fate by interferon-γ.

Interferon (IFN)-γ is a cytokine known for its immunomodulatory and anti-proliferative action. In the liver, IFN-γ can induce hepatocyte apoptosis or inhibit hepatocyte cell cycle progression. This article reviews recent mechanistic reports that describe how IFN-γ may direct the fate of hepatocytes either towards apoptosis or a cell cycle arrest.

The activated aryl hydrocarbon receptor synergizes mitogen-induced murine liver hyperplasia.

Mechanisms of hepatocyte proliferation triggered by tissue loss are distinguishable from those that promote proliferation in the intact liver in response to mitogens. Previous studies demonstrate that exogenous activation of the aryl hydrocarbon receptor (AhR), a soluble ligand-activated transcription factor in the basic helix-loop-helix family of proteins, suppresses compensatory liver regeneration elicited by surgical partial hepatectomy. The goal of the present study was to determine how AhR activation modulates hepatocyte cell cycle progression in the intact liver following treatment with the hepatomitogen, 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP).

Timing is everything: consequences of transient and sustained AhR activity.

The aryl hydrocarbon receptor (AhR) was implicated as a mediator of xenobiotic toxicity over three decades ago. Although a complete picture continues to elude us, investigations by many laboratories during the ensuing period have revealed much about AhR biology in normal physiological processes, as well as the toxicities induced by the dioxins and related polychlorinated aromatic hydrocarbons. The findings are captured in numerous excellent reviews.

Sustained aryl hydrocarbon receptor activity attenuates liver regeneration.

In hepatocyte-derived cell lines, either loss of aryl hydrocarbon receptor (AhR) function or treatment with a persistent AhR agonist such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can disrupt G1 phase cell cycle progression. The present study used liver regeneration to explore mechanistically how AhR activity modulates hepatocyte proliferation in vivo. Treatment of mice with 20 mug/kg TCDD 1 day before 70% partial hepatectomy (PH) resulted in a 50 to 75% suppression in liver regeneration.

The aryl hydrocarbon receptor predisposes hepatocytes to Fas-mediated apoptosis.

Liver homeostasis is achieved by the removal of diseased and damaged hepatocytes and their coordinated replacement to maintain a constant liver cell mass. Cirrhosis, viral hepatitis, and toxic drug effects can all trigger apoptosis in the liver as a means of removing the unwanted cells, and the Fas "death receptor" pathway comprises a major physiological mechanism by which this occurs. The susceptibility to Fas-mediated apoptosis is, in part, a function of the hepatocyte's proteome.

T cell receptor transgenic mice provide novel insights into understanding cellular targets of TCDD: suppression of antibody production, but not the response of CD8(+) T cells, during infection with influenza virus.

Although exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) clearly impairs T cell-dependent immune responses, the mechanisms underlying TCDD-induced T cell dysfunction are unclear. With the goal of determining precisely how exposure to TCDD impairs the activation of CD8(+) T cells in vivo, we used a well-defined T cell receptor (TCR) transgenic system. Greater than 95% of the CD8(+) T cells in F5 transgenic mice possess TCR specific for a peptide from influenza A virus expressed in the context of H-2D(b).

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) renders influenza virus-specific CD8+ T cells hyporesponsive to antigen.

While considerable evidence indicates that exposure to the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs T cell function, the precise mechanism underlying this effect is not well understood. Furthermore, relatively little is known about the effects of TCDD on the fate of activated, antigen-specific T cells in vivo. In the present study, we took advantage of major histocompatibility complex (MHC) class I-restricted tetramers and clonotypic anti-T cell receptor (TCR) antibodies to follow the fate of influenza virus-specific CD8+ T cells in mice treated with TCDD.