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Inflammation has been implicated as an etiological factor in several human cancers. Growing evidence suggests that chronic inflammation may also play a role in the etiology of prostate cancer. Considering that genetic susceptibility is a major risk factor for this disease, we hypothesize that sequence variants in genes that regulate inflammation may modify(More)
In Saccharomyces cerevisiae the CDC14 gene is essential for cell cycle progression. Strains carrying the cdc14-1(ts) allele enter the cell cycle and arrest at restrictive temperatures. We have identified two human cDNAs encoding proteins which share sequence identity to the yeast CDC14p. The cell cycle arrest in cdc14-1(ts) can be specifically complemented(More)
Stable hydrogen isotopic compositions (δD) of compound-specific biomarkers, such as n-alkanes from plant leaf waxes, can be used as a proxy for paleoclimatic change. However, the relationship between hydrogen isotopes of plant leaf wax and plant ecological life forms is not well understood. Here, we report the δD of n-alkanes from 34 modern terrestrial(More)
Inflammatory stimulants such as bacterial endotoxin (lipopolysaccharide (LPS)) are known to induce tissue damage and injury partly through the induction of reactive oxygen species (ROS). Although it is recognized that the induction of ROS in macrophages by LPS depends upon the expression and activation of NADPH oxidase, as well as the suppression of(More)
BACKGROUND Chronic inflammation plays an important role in several human cancers and may be involved in the etiology of prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross-talk between innate immunity and adaptive immunity. Our previous finding of an association of TLR4 gene sequence variants and(More)
Tollip protein serves as a suppressor of innate immunity signaling with unknown mechanism. In this report, we observed that Tollip preferentially bound with phosphatidylinositol-3-phosphate (PtdIns(3)P) and phosphatidylinositol-3,4,5-phosphate (PtdIns(3,4,5)P) in vitro. Mutation of lysine 150 to glutamic acid (Tollip(KE)) within the C2 domain abolished such(More)
The NF-kappaB family plays a crucial role in the pathogenesis of highly lethal septicemia by modulating transcription of many innate and adaptive immunity genes. Two phases of NF-kappaB activation occur: cytosolic activation and nuclear transactivation. Septicemia with multiorgan failure is associated with chronic activation of cytosolic NF-kappaB with(More)
Mitogen-activated protein (MAP) kinase cascades are crucial signal transduction pathways in the regulation of the host inflammatory response to infection. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, plays a pivotal role in the deactivation of p38 and JNK. In vitro studies using cultured macrophages have provided compelling(More)
The interleukin-1 receptor associated kinases (IRAKs) are critically involved in the IL-1R/Toll-like receptor (TLR)-mediated signal transduction processes and therefore regulate cellular innate immune responses. Four IRAK members have been identified in the human genome (IRAK-1, 2, M, and 4), which seem to play distinct roles. Recent studies further suggest(More)
Human Toll-like receptor (TLR) 4 and TLR2 receptors recognize LPS or lipoteichoic acid (LTA), respectively. Prolonged exposure of human macrophages/monocytes to bacterial LPS induces a state of adaptation/tolerance to subsequent LPS challenge. Inflammatory gene expressions such as IL-1beta and TNF-alpha are selectively repressed, while certain(More)