Response to Implants by Finishing Steers at the Time Changes were Made in Program-fed Supplemental Protein

Data from three experiments involving 552 steers that were program fed supplemental protein to more closely meet their requirement were analyzed to determine if changing source or quantity of supplemental protein affected the performance of finishing steers when implanted. Comparisons were made during the beginning portions of the experiments when the cattle were implanted with estradiol benzoate and the last portion of the experiments when they were reimplanted with estradiol benzoate and trenbolone acetate. The diets were also compared during the weigh period immediately after the steers were reimplanted and again during the second weigh period after reimplanting. During the first implant period steers fed soybean meal gained faster and were more efficient than those fed urea, indicating supplementing a corn-based diet with urea did not provide adequate metabolizable protein for optimum performance. However during the second period performance was similar for steers fed soybean meal continuously, changed from soybean meal to urea or fed urea continuously. Steers fed the three diets performed similarly during the initial 21-d period or the second 21-d period following reimplanting with estradiol benzoate and trenbolone acetate. The results of these studies show that the quantity of supplemental protein fed to cattle can be significantly reduced by strategically changing from SBMbased to urea-based supplements and even a low protein urea-supplemented diet without affecting response to anabolic implants

Animal Performance, Storage Losses and Feasibility of Ensiling a Mixture of Tub Ground Low Quality Hay and Wet Distillers’ Grains for Growing Cattle

This study was designed to evaluate long term storage options for wet distillers’ grains including storage losses and performance of backgrounding calves. Thirty six tons of wet distillers’ grains were mixed by mixer wagon with 9 tons of tub ground fescue hay in August of 2007. This mixture packed and stored in a bunker silo, covered with plastic and stored until December at the ISU Beef Nutrition Farm. The mixture was fed to growing cattle and compared to the same feeds mixed daily, and also conventional feeds for a 112 day trial. Performance of all treatments exceeded projections, averaging approximately 3 pounds per day. There were no differences in daily gain or feed conversion among treatments, although cattle fed WDG consumed less feed. Sulfur content of the WDG containing diets exceeded .5% of the diet dry matter. Storage losses were 10.9% for the bunker-stored mixture

Hot nanoindentation in inert environments

An instrument capable of performing nanoindentation at temperatures up to 500 °C in inert atmospheres, including partial vacuum and gas near atmospheric pressures, is described. Technical issues associated with the technique (such as drift and noise) and the instrument (such as tip erosion and radiative heating of the transducer) are identified and addressed. Based on these considerations, preferred operation conditions are identified for testing on various materials. As a proof-of-concept demonstration, the hardness and elastic modulus of three materials are measured: fused silica (nonoxidizing), aluminum, and copper (both oxidizing). In all cases, the properties match reasonably well with published data acquired by more conventional test methods.United States. Office of Naval Research (Contract No. N00014-08-1-0312)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologie

Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.https://nsuworks.nova.edu/hpd_medsci_faculty_books/1002/thumbnail.jp

Gemcitabine and Arabinosylcytosin Pharmacogenomics: Genome-Wide Association and Drug Response Biomarkers

Cancer patients show large individual variation in their response to chemotherapeutic agents. Gemcitabine (dFdC) and AraC, two cytidine analogues, have shown significant activity against a variety of tumors. We previously used expression data from a lymphoblastoid cell line-based model system to identify genes that might be important for the two drug cytotoxicity. In the present study, we used that same model system to perform a genome-wide association (GWA) study to test the hypothesis that common genetic variation might influence both gene expression and response to the two drugs. Specifically, genome-wide single nucleotide polymorphisms (SNPs) and mRNA expression data were obtained using the Illumina 550K® HumanHap550 SNP Chip and Affymetrix U133 Plus 2.0 GeneChip, respectively, for 174 ethnically-defined “Human Variation Panel” lymphoblastoid cell lines. Gemcitabine and AraC cytotoxicity assays were performed to obtain IC50 values for the cell lines. We then performed GWA studies with SNPs, gene expression and IC50 of these two drugs. This approach identified SNPs that were associated with gemcitabine or AraC IC50 values and with the expression regulation for 29 genes or 30 genes, respectively. One SNP in IQGAP2 (rs3797418) was significantly associated with variation in both the expression of multiple genes and gemcitabine and AraC IC50. A second SNP in TGM3 (rs6082527) was also significantly associated with multiple gene expression and gemcitabine IC50. To confirm the association results, we performed siRNA knock down of selected genes with expression that was associated with rs3797418 and rs6082527 in tumor cell and the knock down altered gemcitabine or AraC sensitivity, confirming our association study results. These results suggest that the application of GWA approaches using cell-based model systems, when combined with complementary functional validation, can provide insights into mechanisms responsible for variation in cytidine analogue response

Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models

Background: Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. Methodology/Principal Findings: Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentiallyexpressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (,5%) was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR) and showed significant down-regulation of androgen-regulated genes (p-value = 10 27). Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression

Applications of microarray technology in breast cancer research

Microarrays provide a versatile platform for utilizing information from the Human Genome Project to benefit human health. This article reviews the ways in which microarray technology may be used in breast cancer research. Its diverse applications include monitoring chromosome gains and losses, tumour classification, drug discovery and development, DNA resequencing, mutation detection and investigating the mechanism of tumour development