| Oxygen and Cell Fate Decisions |
27-May-2009 |
10 pages |
| Authors:
Qun Lin; Yuri Kim; Rodolfo M Alarcon; Zhong Yun; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
 | Molecular oxygen has been known to play a critical role in a wide range of biological processes including glycolysis, mitochondrial respiration, angiogenesis, pulmonary functions, and cardiovascular activities. An emerging theme has developed in recent years that oxygen has significant impact on embryonic development, maintenance of stem cells, and cellular differentiation or cell fate decisions. Among the notable observations, early embryonic development takes place in a hypoxic microenvironment. Hematopoietic stem cells ... |
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| Merlin, the Hippo Pathway, and Tumor Suppression in Meningiomas |
07-Feb-2009 |
18 pages |
| Authors:
Anita Lal; Gilson S Baia; CALIFORNIA UNIV SAN FRANCISCO OFFICE OF RESEARCH AFFAIRS
|
| The goal of this proposal was to determine whether merlin exerts its tumor suppressive effects in meningiomas by signaling through the Hippo pathway. Using paired meningioma cell lines, where the only difference is expression of merlin, we have shown that loss of merlin is associated with a clear increase in the protein levels of YAP, a transcriptional coactivator and downstream effector of the Hippo pathway. In addition to this increase, ... |
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| Preparation and Applications of Active Nanostructures as Biosensors |
04-Feb-2009 |
4 pages |
| Authors:
Chung-Yuan Mou; Tien-Sung Lin; NATIONAL TAIWAN UNIV TAIPEI (TAIWAN) DEPT OF CHEMISTRY
|
| This project synthesized active mesoporous silicas with nanospaces to immobilize proteins or fragments of DNA to determine their biosensing utility via electrochemical and spectroscopic methods. |
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| A Two-Dimensional Deoxyribonucleic Acid (DNA) Matrix Based Biomolecular Computing and Memory Architecture |
Feb-2009 |
25 pages |
| Authors:
Anthony Macula; Russell Deaton; Junghuei Chen; STATE UNIV OF NEW YORK AT ALBANY RESEARCH FOUNDATION
|
| The primary goal of this research was the development of an enabling technology for DNA computing. It focused on the development of two distinct DNA-based nanotechnologies, aqueous computing and DNA arrays. Once merged, these DNA-based nanotechnologies serve as a platform for a hybrid silicon-DNA computing architecture. The aqueous side is where the computing happens and the array side is where the results are preprocessed. The array information passes to an ... |
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| Control of Growth Within Drosophila Peripheral Nerves by Ras and Protein Kinase A |
Feb-2009 |
48 pages |
| Authors:
Michael Stern; RICE UNIV HOUSTON TX
|
| The long term goals of this research are to understand the mechanisms by which NF1 and its partners control growth using the Drosophila peripheral nerve as our assay system. This system is advantageous because we can apply a number of powerful molecular genetic methodologies that are not available in other systems. Our major findings were generated from aim #4. We reported after year2 that Ras nonautonomously activates perineurial glial growth ... |
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| Pharmacokinetic Manipulation and Modeling of the Trigger for JP-8-Induced Skin Irritation |
30-Jan-2009 |
36 pages |
| Authors:
James N McDougal; WRIGHT STATE UNIV DAYTON OH DEPT OF PHARMACOLOGY AND TOXICOLOGYY
|
| Dermal exposure to JP-8 has been shown to cause skin irritation in humans and laboratory animals. We have previously investigated the early responses of mammalian skin to liquid JP-8 contact. We have developed a novel in vivo rat model for the investigation of skin irritation, which maintains the interactions and crosstalk of the wide variety of cells in the epidermis and dermis. We have used this model to investigate early ... |
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| Geographical Distribution of Genotypic and Phenotypic Markers Among Bacillus Anthracis Isolates and Related Species by Historical Movement and Horizontal Transfer |
09-Jan-2009 |
8 pages |
| Authors:
J L Kiel; J E Parker; E A Holwitt; R P McCreary; C J DeLos Andrews; A Santos; M Wade; J Kalns; W Walker; AIR FORCE RESEARCH LAB BROOKS CITY-BASE TX
|
| The geographical distribution of Bacillus anthracis strains and isolates bearing some of the same genetic markers as the Amerithrax Ames isolate was examined and evaluated. At least one mechanism for the horizontal movement of genetic markers was shown amongst isolates and closely related species and the effect of such mixing was demonstrated on phenotype. The results provided potential mechanisms by which attempts to attribute isolates of Bacillus anthracis to certain ... |
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| Development of a Nature-Inspired Vector for Targeted Systemic Breast Cancer Gene Therapy |
Jan-2009 |
47 pages |
| Authors:
Arash Hatefi; WASHINGTON STATE UNIV PULLMAN
|
| The purpose of this research was to develop a gene delivery system that can target breast cancer cells specifically and transfect them efficiently. A biomimetic vector was genetically engineered to contain at precise locations: a) an adenovirus micro peptide to condense pDNA into nanosize particles, b) a synthetic peptide to target breast cancer cells, c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and facilitate escape of the nanoparticles ... |
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| Novel Small Molecule Antagonists of the Interaction of the Androgen Receptor and Transcriptional Co-regulators |
Jan-2009 |
34 pages |
| Authors:
Clementine Feau; SAINT JUDE CHILDREN'S RESEARCH HOSPITAL MEMPHIS TN
|
| Androgens, mediated by the Androgen Receptor (AR), play a crucial role in prostate cancer. Current treatments are focused on anti-androgenic drugs competing with natural androgens and antagonizing the transcriptional activity of the AR. Although widely used, these drugs have shown significant side effects and in addition, tumors have become resistant suggesting mutations of the receptor. Regulation of gene expression by AR requires the binding to androgens or to its natural ... |
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| Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GP1 Ectodomain Shedding |
23-Dec-2008 |
19 pages |
| Authors:
Luis M Branco; Alex Matschiner; Joseph N Fair; Megan M Illick; Kerry A Illick; Randal Schoepp; Robert F Garry; Mary C Guttieri; BIOFACTURA INC ROCKVILLE MD
|
| Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1), and glycoprotein 2 (GP2); Immunization of non-human primates with viral vectors expressing the arenaviral glycoprotein complex (GPC) confers full protective immunity against a lethal challenge with LASV. Thus, the development of native or quasi native recombinant LASV GP1 and GP2 as soluble, uncoupled proteins will improve current diagnostics, treatment, and prevention of Lassa ... |
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| Global Survey of Research and Capabilities in Genetically Engineered Organisms That Could be Used in Biological Warfare or Bioterrorism |
Dec-2008 |
63 pages |
| Authors:
Jose-Luis Sagripanti; Christine Griffiths; Ramsbotham; Alan J Jr; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
| This report summarizes the scientific principles underlying genetic modification of microorganisms. It assesses the global availability and cost of technology (know-how, keystone equipment, and synthesized biological materials) needed to acquire and produce potentially lethal biological agents in quantity. The analysis includes technology to engineer novel organisms previously unknown in nature, to synthesize organisms de novo, or to modify naturally pre-existing organisms. The document considers the growing proliferation of legitimate activities, ... |
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| Chirality of Sulforhodamine Dye Molecules Incorporated in DNA Thin Films |
13-Nov-2008 |
4 pages |
| Authors:
K SINGH; A J Steckl; H Spaeth; J Grote; R Naik; CINCINNATI UNIV OH NANOELECTRONICS LAB
|
| Thin films formed from salmon sperm DNA reacted with a cationic surfactant (CTMA-Cl) included up to 25 wt % fluorescent molecule sulforhodamine (SRh). SRh effect on DNA chirality and vice versa was investigated by circular dichroism (CD) spectroscopy. The CD signals at 250-265 nm indicate that DNA chirality was maintained or enhanced. Induced CD (iCD) signal at 580-610 nm indicates that SRh is chiral in DNA/CTMA. iCD signal from both ... |
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| Interfering with DNA Damage Signals: Radiosensitizing Prostate Cancer Using Small Peptides |
01-Nov-2008 |
8 pages |
| Authors:
Bo Xu; SOUTHERN RESEARCH INST BIRMINGHAM AL
|
| The major goal of this project is to identify small inhibitory peptides that can target critical DNA damage responsive pathways in order to develop novel therapeutic agents for prostate cancer radiotherapy. Previously we have demonstrated that small fusion peptides containing SMC1 phosphorylation and NBS1 ATM binding sequences can inhibit ATM activity and decrease prostate tumor cell clonogenic survival after radiation, therefore these peptides can be tested for in vivo activities ... |
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| Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer |
Nov-2008 |
96 pages |
| Authors:
Elena B Pasquale; BURNHAM INST LA JOLLA CA
|
| Mutations have been recently identified in the EphB2 receptor gene in prostate cancer suggesting that EphB2, a member of the large Eph receptor tyrosine kinase family, is a tumor suppressor in prostate cancer. Consistent with a tumor suppressor activity, we found that EphB2 is more highly expressed in non-transformed BPH-1 prostate epithelial cells than in several prostate cancer cell lines. Furthermore, EphB2 expression was rapidly lost in stably transfected DU145 ... |
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| Spatially-Explicit Assessments of Genetic Biodiversity and Dispersal in Gopher Tortoises for Evaluation of Habitat Fragmentation at DoD Sites |
Oct-2008 |
42 pages |
| Authors:
Christopher W Theodorakis; SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE DEPT OF BIOLOGICAL SCIENCES
|
| The objective was to perform a proof of principle assessment of genetic diversity and gene flow of gopher tortoises on Camp Shelby, MS. The specific aims were to determine if there is evidence that military activity affects genetic diversity and gene flow. DNA was extracted from the blood of gopher tortoises collected from 22 colonies in and around Camp Shelby. The amount of genetic diversity in each colony and treatment ... |
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| Assessment of GPR30, a Seven Transmembrane-Spanning Estrogen Receptor, as an Oncogene |
Oct-2008 |
9 pages |
| Authors:
Edward J Filardo; RHODE ISLAND HOSPITAL PROVIDENCE
|
| Expression of the seven transmembrane-spanning receptor (7TMR), GPR30, in primary human breast tumors is positively associated with several tumor progression variables including extra mammary metastases (Filardo et al, 2006). Altered expression of 7TMRs is linked with a spectrum of disease phenotypes, including cancer, raising the possibility that GPR30 may function as an oncogene. To test this hypothesis, two lines of transgenic mice (T6-1A and T6-2E) were engineered with stably integrated ... |
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| DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera |
Oct-2008 |
34 pages |
| Authors:
Jean-Pierre Issa; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Polycythemia vera (PV) is the most common myeloproliferative disorder with a yearly incidence of 28 per 1 million people and a slightly higher prevalence in males. PV is characterized by clonal expansion of erythroid, myelomonocytic, and megakaryocytic lineages, erythrocytosis being the most prominent clinical manifestation of PV. The disease is associated with a significant morbidity and mortality, including thrombotic and/or hemorrhagic events, and a risk of an evolution into myelofibrosis ... |
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| The Identification of Splice Variants as Molecular Markers in Parkinson's Disease |
01-Sep-2008 |
65 pages |
| Authors:
Gloria E Meredith; ROSALIND FRANKLIN UNIV OF MEDICINE AND SCIENCE CHICAGO IL
|
| Purpose: Alternative splicing is responsible for producing several products from a single transcript and can cause pathogenic changes in RNA in neurodegenerative disease. This proposal tests the hypothesis that regulation of normal splicing is disrupted in Parkinson's disease (PD). Scope: Experiments determined splicing products in the brain and blood of experimental MPTP models of PD. The overall goal was to use splice variants as biomarkers to identify individuals at risk ... |
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| Role of STAT5b in Breast Cancer Progression and Metastasis |
01-Sep-2008 |
16 pages |
| Authors:
Teresa Bernaciak; VIRGINIA UNIV CHARLOTTESVILLE
|
| The signal transducer and activator of transcription (STAT) 5b is involved in tumorigenic signaling in a number of cancers including breast cancer. However, its importance in breast cancer migration has not been investigated. This research aims to determine the role of STAT5b in breast cancer migration. Knockdown of STAT5b inhibited migration of human breast cancer cells to serum by 60-80%. This inhibition could be rescued by re-introduction of wild-type STAT5b ... |
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| Interchromosomal Associations that Alter Nf1 Gene Expression can Modify Clinical Manifestations of Neurofibromatosis 1 |
Sep-2008 |
9 pages |
| Authors:
Andrew R Hoffman; PALO ALTO INSTITUTE FOR RESEARCH AND EDUCATION INC CA
|
| We have described a new form of epistasis in which direct, long range, physical interactions between genes, or gene-gene interactions mediated by specialized DNA binding proteins such as CTCF, lead to modification of phenotypic read-out. Using the associated chromatin trap (ACT) and chromosome conformation capture (3C) assays which are designed to assess physical propinquity, we investigated long range interactions of the human NF1 gene that are mediated by CTCF in ... |
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| Spatial and Temporal Population Genetics at Deep-Sea Hydrothermal Vents Along the East Pacific Rise and Galapagos Rift |
Sep-2008 |
208 pages |
| Authors:
Abigail J Fusaro; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
| Ecological processes at deep-sea hydrothermal vents on fast-spreading mid-ocean ridges are punctuated by frequent physical disturbance. Larval dispersal among disjunct vent sites facilitates the persistence of sessile invertebrate species in these geologically and chemically dynamic habitats despite local extinction events. Regional population extension and rapid recolonization by the siboglinid tubeworm Rifliapachyptila have been well documented along the East Pacific Rise and the Galapagos Rift. To analyze spatial and temporal population ... |
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| Faunal Biogeography Community Structure and Genetic Connectivity of North Atlantic Seamounts |
Sep-2008 |
181 pages |
| Authors:
Walter W Cho; WOODS HOLE OCEANOGRAPHIC INSTITUTION MA
|
| The mechanisms of faunal dispersal across ocean basins are key unknowns toward understanding of the modern biogeography and biodiversity of deep-sea fauna. Seamounts are considered to play a defining role in faunal evolution, acting as regional centers of speciation, stepping-stones for dispersal, and/or refugia for deep-sea populations. The overarching goal of this dissertation was to examine the role of seamounts in structuring marine biodiversity and biogeography. This study focused on ... |
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| Immune Response Genotypes and Risk of Young Adult Hodgkin Lymphoma |
Sep-2008 |
11 pages |
| Authors:
Wendy Cozen; Victoria Cortessis; David Conti; David Vandenberg; Bharat Nathwani; Thomas Mack; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Hodgkin lymphoma (HL) is the first and second most common cancer among young women and men 20-39 years old, respectively. Our previous results from a small twin study suggested that an inherited imbalance in the immune response to infection could increase susceptibility to young adult HL. Here we will further test the hypothesis that the susceptible immunophenotype for HL is determined by a genetic tendency toward an exaggerated Th2 and/or ... |
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| Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs |
Sep-2008 |
19 pages |
| Authors:
Tom Kadesch; PENNSYLVANIA UNIV PHILADELPHIA PA RESEARCH SERVICES
|
| This is a final report that presents data obtained during the grant?s duration of funding. The grant addresses the potential role of Notch signaling in the malignant transformation of neurofibromas to MPNSTs in patients with NF1. Our previous work has shown that constitutive expression of Notch can transform rat Schwann cells and that at least on MPNST-derived human Schwann cell line (of three examined) signals via Notch. This report includes ... |
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| The Structural Basis of Pathogen Recognition by TLR Receptors of the Innate Immune System |
Aug-2008 |
21 pages |
| Authors:
Yorgo Modis; YALE UNIV NEW HAVEN CT
|
| The innate immune system is the first line of defense against invading pathogens. The overall goal of this project is to understand how a key family of innate immune receptors, the Toll-like receptors (TLRs), recognize their microbial ligands, and how this recognition is translated into an immune response. This report covers an initial one-year contract in a three-year project. In our first year, we developed methods to purify milligram quantities ... |
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| Environmentally Induced Gene Silencing in Breast Cancer |
01-Jul-2008 |
9 pages |
| Authors:
Mitchell Turker; OREGON HEALTH AND SCIENCES UNIV PORTLAND
|
| The main goal of the study was to test the hypothesis that a reduction in gene expression could induce gene silencing (i.e. relatively stable loss of gene expression) in breast cells. Silencing of a variety of tumor suppressor genes plays a major role in the initiation and progression of breast cancer. Our ultimate goal is to determine if environmentally induced gene repression plays a role as a trigger for the ... |
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| A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb |
Jul-2008 |
6 pages |
| Authors:
Janet Leatherwood; STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
|
| The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus ... |
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| Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a |
Jul-2008 |
13 pages |
| Authors:
Bart M Smits; WISCONSIN UNIV-MADISON
|
| For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression ... |
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| A Combined Nutritional and Immunological Intervention to Activate Natural Cytotoxicity Against Breast Cancer Cells In Vitro and In Vivo |
Jul-2008 |
11 pages |
| Authors:
A C Ross; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| The central hypothesis of this Idea Award is that a combination of nutritional and immunological treatments may work together to stimulate the body's natural immune defenses against breast cancer. We are testing treatment with 3 agents, retinoic acid (RA), a metabolite of the essential nutrient vitamin A, with immune stimulation using alpha-galactosylceramide (-GalCer, a synthetic lipid known to alter immune function and to display antitumorigenic activity in vivo; and poly-I:C ... |
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| A Role for MEK-Interacting Protein 1 (MP1) in Hormone Responsiveness of Estrogen Receptor-Positive Breast Cancer Cells |
Jul-2008 |
12 pages |
| Authors:
Susan E Conrad; MICHIGAN STATE UNIV EAST LANSING
|
| The goals of this research are to test the hypothesis that the small scaffold protein MP1 is required for ER function and proliferation of ER- positive breast cancer cells and to characterize the ER/MP1 complex. MP1 expression was inhibited in several breast cancer cell lines by transfection with MP1-targeting siRNAs. The results obtained demonstrate that MP1 is required for the survival of ER-positive MCF-7 cells but not ER-negative MDA-MB-231 cells. ... |
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| Maintaining Genome Stability: The Role of Helicases and Deaminases |
Jul-2008 |
90 pages |
| Authors:
Xiaojiang Chen; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Both helicases and deaminases are enzymes that play an important role in maintaining genomic stability and immune responses. Errors in duplicating DNA can result in genomic instability, leading to various human diseases, such as cancer, immune system disorder, muscle dystrophy, and neurodegenerations. Thus, maintaining genomic integrity is vital to the normal growth of cells and to human health. Maintenance of genome integrity during S phase depends in part on the ... |
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| ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone |
Jul-2008 |
33 pages |
| Authors:
Guozhi Xiao; PITTSBURGH UNIV PA
|
| During the last year of support (from July 1, 2007 to June 30, 2008), our studies have made significant progresses in all aspects of the study: i) we demonstrate that PTH increases ATF4 expression and activity and ATF4 is required for PTH induction of Ocn expression in osteoblasts. ATF4 is a novel downstream target of PTH signaling in osteoblasts; ii) we show that ATF4 is required for the anabolic actions ... |
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| Symposium FF: Molecular Motors, Nanomachines, and Active Nanostructures |
23-Jun-2008 |
|
| Authors:
Henry Hess; MATERIALS RESEARCH SOCIETY WARRENDALE PA
|
 | This symposium intersects materials research with the other sciences (physics, chemistry, biology and engineering) by bringing together some or the world's foremost scientists who share the fascination of the generation or motion on the nanoscale. The organizers anticipated that this symposium would enable discussions that help identify future directions for the development of molecular machines and inspire collaborative investigations uniquely present in this field. Refer to attached summary and abstracts. ... |
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| Application of a Genetic Algorithm and Multi Agent System to Explore Emergent Patterns of Social Rationality and a Distress-Based Model for Deceit in the Workplace |
01-Jun-2008 |
125 pages |
| Authors:
Jacob F Davis; NAVAL POSTGRADUATE SCHOOL MONTEREY CA
|
| Organizations rely on the honest operation of its members, but in an environment where individual members cannot be observed the opportunity for individuals to lie can lead to dishonest choices (Grover, 1993). This thesis created and applied a computer-based Genetic Algorithm and Multi Agent System in order to test the predictions of Dr. Steven Grover's distress-based model of the antecedents of lying in organizations. Grover's model blends self-interest theories and ... |
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| BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3 |
01-Jun-2008 |
66 pages |
| Authors:
Xiaowei Chen; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCA1 and BRCA2 mutation-negative breast cancer-prone families. We hypothesized that other proteins, which have equivalent or complementary functions as BRCA1, may also be involved in the development of breast cancer. We have recently found one such candidate, referred to as BRCC36. We have reported a profound increase in BRCC36 expression in breast tumors which leads ... |
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| Regulation of Egr1 Target Genes by the Nurd Chromatin Remodeling Complex |
01-Jun-2008 |
20 pages |
| Authors:
John Svaren; WISCONSIN UNIV-MADISON
|
| Previous work had shown that the EGR1 transactivator is over expressed in prostate cancer, while expression of its corepressor, NAB2, is reduced. Based on our recent characterization of an interaction between NAB2 and the NuRD (Nucleosome remodeling and disruption) chromatin remodeling complex, we have determined if loss of NAB2 expression results in loss of NuRD targeting to EGR1 target genes. In progress thus far, we have shown that repression of ... |
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| Killing Breast Cancer Cells through Activation of the Apoptosome |
Jun-2008 |
7 pages |
| Authors:
Sally Kornbluth; DUKE UNIV DURHAM NC
|
| Cells die in response to chemotherapeutic agents by activating a mitochondrial cell death pathway. This pathway leads to activation of proteases known as caspases through the release of cytochrome c from mitochondria. Once released, cytochrome c engages a cytoplasmic receptor known as Apaf-1, which oligomerizes and activates caspase 9. We demonstrated that breast cancer cells have apoptosomes which are hypersensitive to cytochrome c. Thus we have proposed to develop cytoplasmic ... |
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| Evolution in a Test Tube: Exploring the Structure and Function of RNA Probes |
02-May-2008 |
48 pages |
| Authors:
Jeffrey E Vandenengel; NAVAL ACADEMY ANNAPOLIS MD
|
| This Trident project used the new in vitro selection strategy to explore the structure and function of one of the tobramycin beacon aptamers. The question addressed was the following: What are the sequence/structure constraints on a functional tobramycin beacon aptamer? The sequence of the RNA was partially randomized in order to produce a large number of variants related to the original aptamer. Then, the selection for functional molecules was repeated. ... |
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| The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis |
01-May-2008 |
20 pages |
| Authors:
Xiaodong Zhou; TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
|
| During this first year of the project, we established 60 primary fibroblast strains from normal controls and SSc patients who have been genotyped with HLA markers. We performed stimulation assays with silica and/or carbon, titanium particles in 60 primary fibroblast strains. Our results showed that both silica and carbon particle can activate fibroblasts toward fibrotic changes. To develop a comprehensive statistical analysis in study of dynamic properties of fibroblasts, we ... |
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| Regulation of the mTOR Pathway by a Novel Rheb Binding Protein BNIP3 |
01-May-2008 |
19 pages |
| Authors:
Kun-Liang Guan; MICHIGAN UNIV ANN ARBOR
|
| Uncontrolled mTOR activation is a major contributing factor to the pathogenesis of TSC. mTOR is known to be regulated by a wide range of signals such hypoxia. The major goal of this project is to determine mTOR regulation by hypoxia. We proposed to focus on BNIP3 which is a Rheb interacting protein in mTOR regulation in response to hypoxia. Our goals outlined in the original proposal have been successfully completed. ... |
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| Novel Methods for Imaging PET Biomarkers and Gene Therapy of Cancer |
01-May-2008 |
10 pages |
| Authors:
Gabor Tigyi; TENNESSEE UNIV MEMPHIS
|
| Cancer mortality in the USA ranks Tennessee number 43 in incidence and 5th in the nation in mortality both numbers suggesting much work to be done. Altogether, there are over 660,000 citizens with active military or veteran status in our state constituting over 15% of the general population. Therefore, the poor cancer mortality statistics negatively affects not only the state's general population but also military and veteran families living in ... |
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| Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS |
May-2008 |
10 pages |
| Authors:
Stephen B Baylin; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene might predict which DCIS lesions in women would be at risk for the evolution of recurrence and/or emergence of invasive cancer. As the work progressed the concept was expanded to include the DNA methylation status of additional genes for this purpose and also for the purpose of predicting ... |
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| Cytochrome c Gene and Protein Expression: Developmental Regulation, Environmental Response, and Pesticide Sensitivity in Aedes aegypti |
May-2008 |
9 pages |
| Authors:
Kenneth J Linthicum; Julia W Pridgeon; Liming Zhao; James J Becnel; Gary G Clark; AGRICULTURAL RESEARCH SERVICE GAINESVILLE FL CENTER FOR MEDICAL AGRICULTURAL AND VETERINARY ENTOMOLOGY
|
| Cytochrome c is a highly conserved protein that is found in many multicellular and unicellular organisms. Cytochrome c is a critical intermediate in apoptosis: a controlled form of cell death that kills cells as part of their natural process of development and in response to environmental condition. To detect whether cytochrome c of the mosquito Aedes aegypti (L.) (AeaCytC) is developmentally regulated, we used quantitative real-time polymerase chain reaction (PCR) ... |
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| Determinants of Weight Gain in Women with Early-Stage Breast Cancer |
30-Apr-2008 |
35 pages |
| Authors:
Chi-Chen Hong; HEALTH RESEARCH INC BUFFALO NY
|
| Weight gain after breast cancer diagnosis is common, and it has been associated with poorer prognosis. The goals of the study are to examine weight gain in relation to treatment-related changes in sex hormone levels, and to genetic polymorphisms in sex hormone pathways, accounting for potential interactions with energy balance, psychosocial factors, tumor characteristics, cancer treatment, and medication use. Since sex hormones and glucocorticoids regulate body weight and adipose tissue ... |
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| Predicting the Interplay of Epitope Recognition and Evolution in RNA Viruses Under Immune Pressure |
30-Apr-2008 |
13 pages |
| Authors:
Bjoern Peters; Alesandro Sette; Martin Blythe; LA JOLLA INST FOR ALLERGY AND IMMUNOLOGY LA JOLLA CA DIVISION OF VACCINE DISCOVERY
|
| RNA viruses can rapidly mutate, causing therapeutics and vaccines to loose their effectiveness. The long-term goal of this project is to predict such mutations, in order to anticipate their effect and design better therapeutics and vaccines. In the funding period reported here, the specific goal was to build a predictive model of viral escape from immune pressure exerted by monospecific T cells in vitro. This goal was achieved: a general ... |
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| Genome-Wide Chromosomal Targets of Oncogenic Transcription Factors |
01-Apr-2008 |
40 pages |
| Authors:
Vishwanath R Iyer; TEXAS UNIV AT AUSTIN
|
| We proposed to develop a new genomic method named STAGE (Sequence Tag Analysis of Genomic Enrichment) to identify the direct downstream targets of transcription factors important in breast cancer. STAGE was based on high-throughput sequencing of concatamerized tags derived from DNA associated with transcription factors isolated by chromatin immunoprecipitation. We have successfully accomplished the original goals of the project. The advent of next-generation sequencing technologies (Solexa, 454) after the inception ... |
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| Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk |
01-Apr-2008 |
74 pages |
| Authors:
Wan-Yee Tang; CINCINNATI UNIV OH
|
| Estrogens are known to play a role in the initiation and progression of prostate cancer. Recently, environmental factors such as xenoestrogens have been reported on their prevalence of prostate diseases or cancers. Estrogen imprinting of the prostate gland is believed to associate with an increased incidence of prostatic lesions including inflammation, epithelial hyperplasia, squamous metaplasia, dysplasia and adenocarcinoma. And DNA methylation may be one of the possible mechanisms of the ... |
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| The Role of the POZ-ZF Transcription Factor Kaiso in Breast Cell Proliferation and Tumorigenesis |
01-Apr-2008 |
31 pages |
| Authors:
Michelle I Anstey; MCMASTER UNIV HAMILTON (ONTARIO)
|
| Kaiso is a member of the POZ-ZF family of transcription factors, first identified as a binding partner for the p120ctn cell adhesion co-factor. Previous work in our laboratory showed that Kaiso was misexpressed in ~40% of human breast tumors and we also identified cyclin D1 as a putative Kaiso target gene. This project elucidated the mechanism by which Kaiso regulates cyclin D1 expression and the effects of this on breast ... |
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| Identification of Tumor Suppressor Genes by Genetic and Epigenetic Genome-Scanning |
01-Apr-2008 |
64 pages |
| Authors:
Fumiichiro Yamamoto; BURNHAM INST LA JOLLA CA
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| We used systematic multiplex rt-pcr and dna microarray hybridization methods to examine the expression of the genes in the chromosomal regions of 18q21-qter, 8p, and 1p33-pter, which are often decreased in copy number in breast tumors and cell lines derived from breast cancer. We identified dozens of genes in the chromosomal regions whose expression was frequently diminished or lost in breast cancer cell lines that were examined. We confirmed the ... |
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| Identification of Genes Regulating the Development of Breast Cancer |
01-Apr-2008 |
33 pages |
| Authors:
Hua Wang; WISCONSIN UNIV-MADISON
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| We have identified four different modifiers of Apc(min) that affect mammary tumor number or mammary tumor latency (Mmom1-Mmom4). To further investigate the molecular mechanisms of mammary modifiers, Mmom1 and Mmmom2 congenic mice were produced and tested for the effect on mammary tumor number or mammary tumor latency. The effect of Mmom2 on mammary tumor latency was confirmed in the congenic mice and the region containing Mmom2 was narrowed into a ... |
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Genetic Engineering and Molecular Biology
