In the event of an improvised nuclear device detonation, prompt radiation exposure would consist photons plus a neutron component that contribute to total dose. As neutrons cause more complex and difficult repair damage cells result in severe health burden affected individuals, it is paramount be able estimate contribution estimated dose, provide information for those making treatment decisions. Mice exposed either 0.25 or 1 Gy 4 x-ray were sacrificed at 7 days after exposure. Whole genome...

High-dose radiation exposure results in gastrointestinal (GI) acute syndrome identified by the destruction of mucosal layer, intestinal growth barrier dysfunction, and aberrant inflammatory responses. Further, causes gut microbiome dysbiosis characterized diminished microbial diversity, mostly commensal bacteria, spread bacterial pathogens that trigger recruitment immune cells production pro-inflammatory factors lead to further GI tissue damage. Currently, there are no U.S. Food Drug...

The detonation of an improvised nuclear device would produce prompt radiation consisting both photons (gamma rays) and neutrons. While much effort in recent years has gone into the development biodosimetry methods suitable for mass triage, possible effect neutrons on endpoints studied remained largely uninvestigated. We have used a novel neutron irradiator with energy spectrum based that 1–1.5 km from epicenter Hiroshima blast to begin examining global gene expression, impact this may...

Radiation exposure due to the detonation of an improvised nuclear device remains a major security concern. from such involves combination photons and neutrons. Although will make greater contribution total dose, neutrons certainly have impact on severity as they high relative biological effectiveness.We investigated gene expression signatures in blood mice exposed 3 Gy x-rays, 0.75 neutrons, or mixed field photon/neutron with neutron fraction contributing 5, 15%, 25% radiation dose. Gene...

Abstract Prostate cancer is the second most common type of and leading cause death in American men. RAD9 stabilizes genome, but prostate cells tumors often have high quantities protein. Reduction level within decreases tumorigenicity nude mouse xenographs metastasis phenotypes culture, indicating that overproduction essential for disease. In DU145 cells, CpG hypermethylation a transcription suppressor site intron 2 causes high-level gene expression. Herein, we demonstrate DNA...

Raf-1 serine/threonine protein kinase plays an important role in cell survival, proliferation, and migration; however, the specific targets of diverse cellular processes are not clearly defined. Myosin phosphatase activity is critical to regulation cytoskeletal reorganization, cytokinesis, motility. Here, we describe association with myosin phosphorylation regulatory myosin-binding subunit (MBS) by Raf-1. Treatment cells phorbol 12-myristate 13-acetate has been shown stimulate kinase. To...

Raf-1 protein serine/threonine kinase plays an important role in ERK signal transduction pathway of cell survival and proliferation. Raf-induced transcriptional changes are dependent on phosphorylation/activation ERK. However, regulation phospho-ERK (p-ERK) via Raf transcriptome is as yet unknown. We report the initial characterization BRCC3, a novel gene discovered previously by mRNA expression profiling MDA-MB 231 human breast cancer cells treated with antisense oligonucleotide. BRCC3...

In the possible event of a detonation an improvised nuclear device (IND), immediate radiation would consist both photons (gamma rays) and neutrons. Since neutrons generally have high relative biological effectiveness (RBE) for most physiological end points, it is important to understand effect that on biodosimetry methods are being developed medical triage purposes. We previously compared transcriptomic response in human blood after neutron photon irradiation. this study, we analyzed...

The cDNA encoding rat brain cytosolic acyl-CoA thioester hydrolase (ACT) has been cloned and sequenced, the primary structure of enzyme deduced. A partial amino acid sequence (38 acids) was determined using peptides generated after CNBr digestion purified enzyme. Primers synthesized on basis this information were used to isolate two clones, each full length nucleotide sequences these clones contained an open reading frame a 358-amino polypeptide with calculated molecular mass 39.7 kDa,...

Rat brain cytosolic acyl-CoA hydrolase has been purified 3,500-fold to apparent homogeneity using heat treatment, ammonium sulfate fractionation followed by anion exchange, hydrophobic interaction, and hydroxyapatite c chromatography. The enzyme remains stable only in the presence of a high concentration (30%, vol/vol) ethylene glycol. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows single band 40.9 kDa. However, on high-performance size-exclusion chromatography migration...

Abstract Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family proteins. This study was designed to investigate mechanism BLID-induced apoptosis and assess significance expression in breast cancer. Experimental Design: The interaction between Bcl-XL examined using vitro transcription/translation, coimmunoprecipitation, immunoflourescence assays. relationship mRNA pathologic measures cancer specimens (n = 55) publicly available ONCOMINE microarray database....

RAD9A plays an important role in prostate tumorigenesis and metastasis-related phenotypes. The protein classically functions as part of the RAD9A-HUS1-RAD1 complex but can also act independently. selectively transactivate multiple genes, including CDKN1A NEIL1 by binding p53-consensus sequences or near promoters. is overexpressed human cancer specimens cell lines; its expression correlates with tumor progression. Silencing cells impairs their ability to form tumors vivo migrate well grow...

Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to biodosimetry. However, age and sex could potentially limit the accuracy of approach. In this study, we determined impact on peripheral blood cell profile female mice exposed identified differences similarities with previously obtained transcriptomic signature male mice. Young (2 months) old (24 were irradiated 4 Gy X-rays, total RNA was isolated from 24 hours later...

BACKGROUND Mouse embryonic stem cells null for Rad9 are sensitive to deleterious effects of ionizing radiation exposure. Likewise, integrin β1 is a known radioprotective factor. Previously, we showed that RAD9 downregulation in human prostate cancer reduces protein levels and ectopic expression Mrad9 restores inherent high levels. METHODS We used RNA interference knockdown PC3 DU145 cells. These were then exposed radiation, measured by immunoblotting. Survival irradiated was clonogenicity,...

After a large-scale radiological or nuclear event, hundreds of thousands people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure moderate doses (2-6 Gy) can lead the hematopoietic acute syndrome, in which bone marrow (BM) is severely compromised, severe hemorrhage infection are common. Previously, we have developed panel intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 TSPYL2), designed reconstruct absorbed dose from human peripheral...

Abstract As a radiation biodosimetry tool, gene expression profiling is being developed using mouse and human peripheral blood models. The impact of dose, dose-rate, quality has been studied with the goal predicting radiological tissue injury. In this study, we determined aging on profile from mice exposed to radiation. Young (2 mo) old (21 male were irradiated 4 Gy x-rays, total RNA was isolated whole 24 h later, subjected genome microarray analysis. Pathway analysis differentially...

Prostate cancer is a complex disease, with multiple subtypes and clinical presentations. Much progress has been made in recent years to understand the underlying genetic basis that drives prostate cancer. Such mechanistic information useful for development of novel therapeutic targets, identify biomarkers early detection or distinguish between aggressive indolent predict treatment outcome. Multiple tests have become available address these needs We describe several assays, summarizing test...